View source for Medicine:Immunoglobulin therapy

{{Short description|Medical treatment}}
{{Split|normal human immunoglobulin|discuss=Talk:Immunoglobulin therapy#Split|date=December 2020}}
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| pronounce         =
| tradename         = Flebogamma, Gammagard, Hizentra, others
| Drugs.com         = {{Drugs.com|monograph|immune-globulin}}
| MedlinePlus       =
| DailyMedID        = Immune globulin
| pregnancy_AU      = 
| pregnancy_AU_comment = Exempt<ref name="Xembify APMDS" />
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| routes_of_administration = [[Chemistry:Intravenous therapy|Intravenous]], [[Biology:Intramuscular injection|intramuscular]], [[Medicine:Subcutaneous injection|subcutaneous]]
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| ATC_prefix        = J06
| ATC_suffix        = BA
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| legal_AU = S4
| legal_AU_comment = <ref name="Xembify APMDS">{{cite web | title=Xembify APMDS | website=Therapeutic Goods Administration (TGA) | date=15 July 2022 | url=https://www.tga.gov.au/resources/auspmd/xembify | access-date=17 July 2022 | archive-date=14 July 2022 | archive-url=https://web.archive.org/web/20220714222420/https://www.tga.gov.au/apm-summary/xembify | url-status=live }}</ref><ref>{{cite web | title=Prescription medicines: registration of new chemical entities in Australia, 2016 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/prescription-medicines-registration-new-chemical-entities-australia-2016 | access-date=10 April 2023 | archive-date=10 April 2023 | archive-url=https://web.archive.org/web/20230410065503/https://www.tga.gov.au/prescription-medicines-registration-new-chemical-entities-australia-2016 | url-status=live }}</ref><ref>{{cite web | title=Prescription medicines: registration of new chemical entities in Australia, 2014 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/resources/resource/guidance/prescription-medicines-registration-new-chemical-entities-australia-2014 | access-date=10 April 2023 | archive-date=10 April 2023 | archive-url=https://web.archive.org/web/20230410065838/https://www.tga.gov.au/resources/resource/guidance/prescription-medicines-registration-new-chemical-entities-australia-2014 | url-status=live }}</ref>
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| legal_BR_comment =
| legal_CA = Rx-only
| legal_CA_comment = <ref>{{cite web | title=Regulatory Decision Summary - Xembify | website=Health Canada | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/regulatory-decision-summary-detail.php?lang=en&linkID=RDS00596 | access-date=7 June 2022 | archive-date=7 June 2022 | archive-url=https://web.archive.org/web/20220607034842/https://hpr-rps.hres.ca/reg-content/regulatory-decision-summary-detail.php?lang=en&linkID=RDS00596 | url-status=live }}</ref><ref>{{cite web | title=Summary Basis of Decision - HyQvia | website=Health Canada | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00592&lang=en | access-date=6 August 2022}}</ref>
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| legal_US = Rx-only
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| legal_EU = Rx-only
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| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV-->
| legal_UN_comment =
| legal_status      = Rx-only

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| CAS_number        = 9007-83-4
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| ChemSpiderID      = none
| UNII              = 66Y330CJHS
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| synonyms          = normal human immunoglobulin (HNIG), human normal immunoglobulin (HNIG)

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<!-- Definition and medical uses -->
'''Immunoglobulin therapy''' is the use of a mixture of [[Biology:Antibodies|antibodies]] ('''normal human immunoglobulin''' or '''NHIG''') to treat several health conditions.<ref name=AHFS2017/><ref name=BNF69>{{cite book|title=British national formulary : BNF 69|date=2015|publisher=British Medical Association|isbn=9780857111562|pages=867–71|edition=69}}</ref> These conditions include primary immunodeficiency, [[Medicine:Immune thrombocytopenic purpura|immune thrombocytopenic purpura]], [[Medicine:Chronic inflammatory demyelinating polyneuropathy|chronic inflammatory demyelinating polyneuropathy]], [[Medicine:Kawasaki disease|Kawasaki disease]], certain cases of HIV/AIDS and [[Medicine:Measles|measles]], Guillain-Barré syndrome, and certain other infections when a more specific immunoglobulin is not available.<ref name=AHFS2017/> Depending on the formulation it can be given by injection into muscle, a vein, or [[Medicine:Subcutaneous injection|under the skin]].<ref name=AHFS2017>{{cite web|title=Immune Globulin|url=https://www.drugs.com/monograph/immune-globulin.html|publisher=The American Society of Health-System Pharmacists|access-date=8 January 2017|url-status=live|archive-url=https://web.archive.org/web/20170109190342/https://www.drugs.com/monograph/immune-globulin.html|archive-date=9 January 2017}}</ref> The effects last a few weeks.<ref name=BNF69/>

<!-- Side effects and mechanism -->
Common side effects include pain at the site of injection, muscle pain, and allergic reactions.<ref name=AHFS2017/> Other severe side effects include kidney problems, [[Medicine:Anaphylaxis|anaphylaxis]], blood clots, and red blood cell breakdown.<ref name=AHFS2017/> Use is not recommended in people with some types of IgA deficiency.<ref name=AHFS2017/> Use appears to be relatively safe during [[Medicine:Pregnancy|pregnancy]].<ref name=AHFS2017/> Human immunoglobulin is made from human [[Biology:Blood plasma|blood plasma]].<ref name=AHFS2017/> It contains antibodies against many viruses.<ref name=BNF69/>

<!-- History and culture -->
Human immunoglobulin therapy first occurred in the 1930s and a formulation for injection into a vein was approved for medical use in the United States in 1981.<ref>{{cite book| vauthors = Etzioni A, Ochs HD |title=Primary Immunodeficiency Disorders: A Historic and Scientific Perspective|date=2014|publisher=Academic Press|isbn=9780124115545|pages=283–84|url=https://books.google.com/books?id=SF9zAwAAQBAJ&pg=PA283|language=en|url-status=live|archive-url=https://web.archive.org/web/20170109185347/https://books.google.ca/books?id=SF9zAwAAQBAJ&pg=PA283|archive-date=9 January 2017}}</ref> It is on the [[Medicine:WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 |  publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref><ref name="WHO22nd">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 22nd list (2021) | year = 2021 | hdl = 10665/345533 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2021.02 | hdl-access=free }}</ref> Each formulation of the product is somewhat different.<ref name=BNF69/> A number of specific immunoglobulin formulations are also available including for hepatitis B, [[Medicine:Rabies immunoglobulin|rabies]], tetanus, varicella infection, and [[Biology:Rho(D) immune globulin|Rh positive blood exposure]].<ref name=BNF69/>

== Medical uses ==
Immunoglobulin therapy is used in a variety of conditions, many of which involve decreased or abolished antibody production capabilities, which range from a complete absence of multiple types of antibodies, to IgG subclass deficiencies (usually involving IgG2 or IgG3), to other disorders in which antibodies are within a normal quantitative range, but lacking in quality – unable to respond to antigens as they normally should – resulting in an increased rate or increased severity of infections. In these situations, immunoglobulin infusions confer passive resistance to infection on their recipients by increasing the quantity/quality of [[Biology:Immunoglobulin G|IgG]] they possess. Immunoglobulin therapy is also used for a number of other conditions, including in many autoimmune disorders such as [[Medicine:Dermatomyositis|dermatomyositis]] in an attempt to decrease the severity of symptoms. Immunoglobulin therapy is also used in some treatment protocols for [[Biology:Immunosuppression|secondary immunodeficiencies]] <!-- not an ideal link target --> such as human immunodeficiency virus (HIV), some autoimmune disorders (such as immune thrombocytopenia and [[Medicine:Kawasaki disease|Kawasaki disease]]), some neurological diseases ([[Medicine:Multifocal motor neuropathy|multifocal motor neuropathy]], stiff person syndrome, multiple sclerosis and [[Medicine:Myasthenia gravis|myasthenia gravis]]) some acute infections and some complications of organ transplantation.<ref name="aireview">{{cite journal | vauthors = Orange JS, Hossny EM, Weiler CR, Ballow M, Berger M, Bonilla FA, Buckley R, Chinen J, El-Gamal Y, Mazer BD, Nelson RP, Patel DD, Secord E, Sorensen RU, Wasserman RL, Cunningham-Rundles C | title = Use of intravenous immunoglobulin in human disease: a review of evidence by members of the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma and Immunology | journal = The Journal of Allergy and Clinical Immunology | volume = 117 | issue = 4 Suppl | pages = S525–S553 | date = April 2006 | pmid = 16580469 | doi = 10.1016/j.jaci.2006.01.015 | type = Review | doi-access = free | title-link = doi }}</ref>

Immunoglobulin therapy is especially useful in some acute infection cases such as pediatric [[Biology:HIV|HIV]] infection and is also considered the standard of treatment for some autoimmune disorders such as [[Medicine:Guillain–Barré syndrome|Guillain–Barré syndrome]].<ref name=gbs>{{cite journal | vauthors = van Doorn PA, Kuitwaard K, Walgaard C, van Koningsveld R, Ruts L, Jacobs BC | title = IVIG treatment and prognosis in Guillain-Barré syndrome | journal = Journal of Clinical Immunology | volume = 30 | issue = S1 | pages = S74–S78 | date = May 2010 | pmid = 20396937 | pmc = 2883091 | doi = 10.1007/s10875-010-9407-4 }}</ref><ref name="gbs2">{{cite journal | vauthors = Hughes RA, Wijdicks EF, Barohn R, Benson E, Cornblath DR, Hahn AF, Meythaler JM, Miller RG, Sladky JT, Stevens JC | title = Practice parameter: immunotherapy for Guillain-Barré syndrome: report of the Quality Standards Subcommittee of the American Academy of Neurology | journal = Neurology | volume = 61 | issue = 6 | pages = 736–740 | date = September 2003 | pmid = 14504313 | doi = 10.1212/WNL.61.6.736 | s2cid = 20577426 | doi-access = free | title-link = doi }}</ref> The high demand which coupled with the difficulty of producing immunoglobulin in large quantities has resulted in increasing global shortages, usage limitations and rationing of immunoglobulin.<ref name="shortage">{{cite journal | vauthors = Pondrom S | title = The IVIg dilemma | journal = American Journal of Transplantation | volume = 14 | issue = 10 | pages = 2195–2196 | date = October 2014 | pmid = 25231064 | doi = 10.1111/ajt.12995 | s2cid = 221433035 | department = The AJT Report | doi-access = free | title-link = doi }}</ref>

=== United Kingdom ===
The United Kingdom's National Health Service recommends the routine use of immunoglobulin for a variety of conditions including primary immunodeficiencies and a number of other conditions, but recommends against the use of immunoglobulin in [[Medicine:Sepsis|sepsis]] (unless a specific toxin has been identified), multiple sclerosis, neonatal sepsis, and pediatric HIV/AIDS.<ref name=NHS>{{cite web|title=Clinical Guidelines for Immunoglobulin Use|url=http://www.ivig.nhs.uk/documents/dh_129666.pdf|website=National Health Service|access-date=5 December 2015|url-status=live|archive-url=https://web.archive.org/web/20150529042116/http://www.ivig.nhs.uk/documents/dh_129666.pdf|archive-date=29 May 2015}}</ref>

=== United States ===
The American Academy of Allergy, Asthma, and Immunology supports the use of immunoglobulin for primary immunodeficiencies, while noting that such usage actually accounts for a minority of usage and acknowledging that immunoglobulin supplementation can be appropriately used for a number of other conditions,<ref name=aaai1>{{cite web|title=Eight guiding principals for safe, effective and appropriate use of IVIG|url=https://www.aaaai.org/Aaaai/media/MediaLibrary/PDF%20Documents/Practice%20Resources/IVIG-guiding-principles.pdf|publisher=American Association of Allergists and Immunologists|access-date=5 December 2015|url-status=live|archive-url=https://web.archive.org/web/20160305025940/https://www.aaaai.org/Aaaai/media/MediaLibrary/PDF%20Documents/Practice%20Resources/IVIG-guiding-principles.pdf|archive-date=5 March 2016}}</ref> including neonatal sepsis (citing a sixfold decrease in mortality), considered in cases of HIV (including pediatric HIV), considered as a second line treatment in relapsing-remitting multiple sclerosis, but recommending against its use in such conditions as [[Medicine:Chronic fatigue syndrome|chronic fatigue syndrome]], [[Medicine:PANDAS|PANDAS]] (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection) until further evidence to support its use is found (though noting that it may be useful in PANDAS patients with an autoimmune component), cystic fibrosis, and a number of other conditions.<ref name="aireview" />

Brands include
* Alyglo (immune globulin intravenous human-stwk)<ref>{{cite web | title=Alyglo | website=U.S. [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA) | date=15 December 2023 | url=https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/alyglo | access-date=22 December 2023}}</ref>
* Asceniv (immune globulin intravenous, human – slra)<ref>{{cite web | title=Asceniv – human immunoglobulin g liquid | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d74f4360-3b51-496c-96fb-84c3976958d2 | access-date=9 June 2021 | archive-date=9 June 2021 | archive-url=https://web.archive.org/web/20210609173255/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d74f4360-3b51-496c-96fb-84c3976958d2 | url-status=live }}</ref>
* Bivigam (immune globulin intravenous – human 10% liquid)<ref>{{cite web | title=Bivigam (immune globulin intravenous – human 10% liquid | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a2244aa0-a6d0-11df-b385-0002a5d5c51b | access-date=9 June 2021 | archive-date=9 June 2021 | archive-url=https://web.archive.org/web/20210609173253/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a2244aa0-a6d0-11df-b385-0002a5d5c51b | url-status=live }}</ref>
* Gamunex-C, (immune globulin injection human)<ref>{{cite web | title=Gamunex-C (immune globulin – human injection | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ade6b84a-e95b-0a49-3296-f56208fdf35b | access-date=9 June 2021 | archive-date=9 June 2021 | archive-url=https://web.archive.org/web/20210609173254/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ade6b84a-e95b-0a49-3296-f56208fdf35b | url-status=live }}</ref>
* Hizentra (immune globulin subcutaneous human)<ref>{{cite web | title=Hizentra – human immunoglobulin g liquid | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7b58f5ff-0316-49a3-b585-1f6003ddb953 | access-date=9 June 2021 | archive-date=9 June 2021 | archive-url=https://web.archive.org/web/20210609173252/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7b58f5ff-0316-49a3-b585-1f6003ddb953 | url-status=live }}</ref>
* Hyqvia (immune globulin 10 percent – human with recombinant human hyaluronidase)<ref>{{cite web | title=Hyqvia (immune globulin 10 percent – human with recombinant human hyaluronidase kit | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7ca2c26f-4be2-48cd-be5b-486e350654ba | access-date=9 June 2021 | archive-date=5 August 2020 | archive-url=https://web.archive.org/web/20200805002533/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7ca2c26f-4be2-48cd-be5b-486e350654ba | url-status=live }}</ref>
* Octagam (immune globulin intravenous, human)<ref>{{cite web | title=Octagam immune globulin (human) – immune globulin solution | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=de00abeb-d635-eddc-b603-10708ecef5aa | access-date=9 June 2021 | archive-date=9 June 2021 | archive-url=https://web.archive.org/web/20210609173301/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=de00abeb-d635-eddc-b603-10708ecef5aa | url-status=live }}</ref><ref>{{cite web | title=Octagam immune globulin (human) – immune globulin solution | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a36a12dc-16be-b135-466f-393954f428a7 | access-date=9 June 2021 | archive-date=9 June 2021 | archive-url=https://web.archive.org/web/20210609173259/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a36a12dc-16be-b135-466f-393954f428a7 | url-status=live }}</ref>
* Panzyga (immune globulin intravenous, human – ifas)<ref>{{cite web | title=Panzyga (immune globulin intravenous – human solution | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=68a5ee5f-0352-b3ae-3321-c0a22947a31d | access-date=9 June 2021 | archive-date=9 June 2021 | archive-url=https://web.archive.org/web/20210609173303/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=68a5ee5f-0352-b3ae-3321-c0a22947a31d | url-status=live }}</ref>
* Xembify (immune globulin subcutaneous, human – klhw)<ref>{{cite web | title=Xembify – immune globulin subcutaneous, human-klhw solution | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8c174b11-a061-412e-a3b2-7bf7e1adaace | access-date=9 June 2021 | archive-date=9 June 2021 | archive-url=https://web.archive.org/web/20210609173304/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8c174b11-a061-412e-a3b2-7bf7e1adaace | url-status=live }}</ref>

=== Canada ===
The National Advisory Committee on Blood and Blood Products of Canada (NAC) and Canadian Blood Services have also developed their own separate set of guidelines for the appropriate use of immunoglobulin therapy, which strongly support the use of immunoglobulin therapy in primary immunodeficiencies and some complications of HIV, while remaining silent on the issues of sepsis, multiple sclerosis, and chronic fatigue syndrome.<ref name="canada">{{cite journal | vauthors = Anderson D, Ali K, Blanchette V, Brouwers M, Couban S, Radmoor P, Huebsch L, Hume H, McLeod A, Meyer R, Moltzan C, Nahirniak S, Nantel S, Pineo G, Rock G | title = Guidelines on the use of intravenous immune globulin for hematologic conditions | journal = Transfusion Medicine Reviews | volume = 21 | issue = 2 Suppl 1 | pages = S9-56 | date = April 2007 | pmid = 17397769 | doi = 10.1016/j.tmrv.2007.01.001 }}</ref>

===Australia===
The Australian Red Cross Blood Service developed their own guidelines for the appropriate use of immunoglobulin therapy in 1997.<ref>{{cite web |title=Criteria for the Clinical Use of Intravenous Immunoglobulin in Australia {{!}} National Blood Authority |url=https://www.blood.gov.au/ivig-criteria |website=www.blood.gov.au |access-date=14 November 2019 |archive-date=1 March 2020 |archive-url=https://web.archive.org/web/20200301054106/https://www.blood.gov.au/ivig-criteria |url-status=live }}</ref> Immunoglobulin is funded under the National Blood Supply and indications are classified as either an established or emerging therapeutic role or conditions for which immunoglobulin use is in exceptional circumstances only.<ref>{{cite web |title=Access to Intravenous Immunoglobulin (IVIg) |url=https://www.blood.gov.au/Intravenous-Ig |website=National Blood Authority |access-date=14 November 2019 |archive-date=2 April 2020 |archive-url=https://web.archive.org/web/20200402055749/https://www.blood.gov.au/Intravenous-Ig |url-status=live }}</ref>

Subcutaneous immunoglobulin access programs have been developed to facilitate hospital based programs.<ref>{{cite web |title=Access to Subcutaneous Immunoglobulin (SCIg) |url=https://www.blood.gov.au/SCIg |website=National Blood Authority |access-date=14 November 2019 |archive-date=1 March 2020 |archive-url=https://web.archive.org/web/20200301054655/https://www.blood.gov.au/SCIg |url-status=live }}</ref>

Human normal immunoglobulin (human immunoglobulin G) (Cutaquig) was approved for medical use in Australia in May 2021.<ref name="Cutaquig APM summary">{{cite web | title=Cutaquig | website=Therapeutic Goods Administration (TGA) | date=12 May 2021 | url=https://www.tga.gov.au/apm-summary/cutaquig | access-date=6 September 2021 | archive-date=6 September 2021 | archive-url=https://web.archive.org/web/20210906213353/https://www.tga.gov.au/apm-summary/cutaquig | url-status=live }}</ref>

=== European Union ===
Brands include HyQvia (human normal immunoglobulin), Privigen (human normal immunoglobulin (IVIg)), Hizentra (human normal immunoglobulin (SCIg)), Kiovig (human normal immunoglobulin), and Flebogamma DIF (human normal immunoglobulin).<ref name="HyQvia EPAR">{{cite web | title=HyQvia EPAR | website=[[Organization:European Medicines Agency|European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/hyqvia | access-date=14 July 2020 | archive-date=15 July 2020 | archive-url=https://web.archive.org/web/20200715021548/https://www.ema.europa.eu/en/medicines/human/EPAR/hyqvia | url-status=live }}</ref><ref name="Hizentra EPAR" /><ref name="Privigen EPAR">{{cite web | title=Privigen EPAR | website=[[Organization:European Medicines Agency|European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/privigen | access-date=14 July 2020 | archive-date=15 July 2020 | archive-url=https://web.archive.org/web/20200715021009/https://www.ema.europa.eu/en/medicines/human/EPAR/privigen | url-status=live }}</ref><ref name="Kiovig EPAR">{{cite web | title=Kiovig EPAR | website=[[Organization:European Medicines Agency|European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/kiovig | access-date=14 July 2020 | archive-date=17 July 2020 | archive-url=https://web.archive.org/web/20200717013809/https://www.ema.europa.eu/en/medicines/human/EPAR/kiovig | url-status=live }}</ref>

In the EU human normal immunoglobulin (SCIg) (Hizentra) is used in people whose blood does not contain enough antibodies (proteins that help the body to fight infections and other diseases), also known as immunoglobulins.<ref name="Hizentra EPAR">{{cite web | title=Hizentra EPAR | website=[[Organization:European Medicines Agency|European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/hizentra | access-date=2 May 2020 | archive-date=1 August 2020 | archive-url=https://web.archive.org/web/20200801233153/https://www.ema.europa.eu/en/medicines/human/EPAR/hizentra | url-status=live }} Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> It is used to treat the following conditions:
* primary immunodeficiency syndromes (PID, when people are born with an inability to produce enough antibodies);<ref name="Hizentra EPAR" />
* low levels of antibodies in the blood in people with chronic lymphocytic leukaemia (a cancer of a type of white blood cell) or myeloma (a cancer of another type of white blood cell) and who have frequent infections;<ref name="Hizentra EPAR" />
* low levels of antibodies in the blood in people before or after allogeneic haematopoietic stem cell transplantation (a procedure where the patient's bone marrow is cleared of cells and replaced by stem cells from a donor);<ref name="Hizentra EPAR" />
* chronic inflammatory demyelinating polyneuropathy (CIDP). In this rare disease, the immune system (the body's defence system) works abnormally and destroys the protective covering over the nerves.<ref name="Hizentra EPAR" />

It is indicated for replacement therapy in adults and children in primary immunodeficiency syndromes such as:
* congenital agammaglobulinaemia and hypogammaglobulinaemia (low levels of antibodies);<ref name="Hizentra EPAR" />
* common variable immunodeficiency;<ref name="Hizentra EPAR" />
* severe combined immunodeficiency;<ref name="Hizentra EPAR" />
* immunoglobulin-G-subclass deficiencies with recurrent infections;<ref name="Hizentra EPAR" />
* replacement therapy in myeloma or chronic lymphocytic leukaemia with severe secondary hypogammaglobulinaemia and recurrent infections.<ref name="Hizentra EPAR" />

Flebogamma DIF is indicated for the replacement therapy in adults, children and adolescents (0–18 years) in:
* primary immunodeficiency syndromes with impaired antibody production;<ref name="Flebogamma DIF">{{cite web | title=Flebogamma DIF | website=[[Organization:European Medicines Agency|European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/flebogamma-dif | access-date=15 July 2020 | archive-date=15 July 2020 | archive-url=https://web.archive.org/web/20200715105531/https://www.ema.europa.eu/en/medicines/human/EPAR/flebogamma-dif | url-status=live }} Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref>
* hypogammaglobulinaemia (low levels of antibodies) and recurrent bacterial infections in patients with chronic lymphocytic leukaemia (a cancer of a type of white blood cell), in whom prophylactic antibiotics have failed;<ref name="Flebogamma DIF" />
* hypogammaglobulinaemia (low levels of antibodies) and recurrent bacterial infections in plateau-phase-multiple-myeloma (another cancer of a type of white blood cell) patients who failed to respond to pneumococcal immunisation;<ref name="Flebogamma DIF" />
* hypogammaglobulinaemia (low levels of antibodies) in patients after allogenic haematopoietic-stem-cell transplantation (HSCT) (when the patient receives stem cells from a matched donor to help restore the bone marrow);<ref name="Flebogamma DIF" />
* congenital acquired immune deficiency syndrome (AIDS) with recurrent bacterial infections.<ref name="Flebogamma DIF" />

and for the immunomodulation in adults, children and adolescents (0–18 years) in:
* primary immune thrombocytopenia (ITP), in patients at high risk of bleeding or prior to surgery to correct the platelet count;<ref name="Flebogamma DIF" />
* Guillain–Barré syndrome, which causes multiple inflammations of the nerves in the body;<ref name="Flebogamma DIF" />
* Kawasaki disease, which causes multiple inflammation of several organs in the body.<ref name="Flebogamma DIF" />

== Side effects ==
Although immunoglobulin is frequently used for long periods of time and is generally considered safe, immunoglobulin therapy can have severe adverse effects, both localized and systemic. Subcutaneous administration of immunoglobulin is associated with a lower risk of both systemic and localized risk when compared to intravenous administration (hyaluronidase-assisted subcutaneous administration is associated with a greater frequency of adverse effects than traditional subcutaneous administration but still a lower frequency of adverse effects when compared to intravenous administration). Patients who are receiving immunoglobulin and experience adverse events are sometimes recommended to take acetaminophen and [[Chemistry:Diphenhydramine|diphenhydramine]] before their infusions to reduce the rate of adverse effects. Additional premedication may be required in some instances (especially when first getting accustomed to a new dosage), [[Chemistry:Prednisone|prednisone]] or another oral steroid.{{citation needed|date=December 2021}}

Local side effects of immunoglobulin infusions most frequently include an injection site reaction (reddening of the skin around the injection site), itching, rash, and hives.<ref name=dyna>{{cite web|title=Immune Globulin|url=http://www.dynamed.com/topics/dmp~AN~T356495/Immune-Globulin#Contraindications-Warnings|website=Dynamed|access-date=23 November 2015|url-status=live|archive-url=https://web.archive.org/web/20151208192710/http://www.dynamed.com/topics/dmp~AN~T356495/Immune-Globulin#Contraindications-Warnings|archive-date=8 December 2015|url-access=subscription}}{{Subscription or libraries|s}}</ref> Less serious systemic side effects to immunoglobulin infusions include an increased heart rate, hyper or hypotension, an increased body temperature, diarrhea, nausea, abdominal pain, vomiting, arthralgia or myalgia, dizziness, headache, fatigue, fever, and pain.<ref name=dyna/>

Serious side effects of immunoglobulin infusions include chest discomfort or pain, [[Medicine:Myocardial infarction|myocardial infarction]], [[Medicine:Tachycardia|tachycardia]], [[Medicine:Hyponatremia|hyponatremia]], [[Medicine:Hemolysis|hemolysis]], hemolytic anemia, [[Medicine:Thrombosis|thrombosis]], [[Medicine:Hepatitis|hepatitis]], [[Medicine:Anaphylaxis|anaphylaxis]], backache, aseptic meningitis, [[Medicine:Acute kidney injury|acute kidney injury]], hypokalemic nephropathy, [[Medicine:Pulmonary embolism|pulmonary embolism]], and transfusion related acute lung injury.<ref name=dyna/> There is also a small chance that even given the precautions taken in preparing immunoglobulin preparations, an immunoglobulin infusion may pass a virus to its recipient.<ref name=dyna/> Some immunoglobulin solutions also contain isohemagglutinins, which in rare circumstances can cause hemolysis by the isohemagglutinins triggering phagocytosis.<ref>{{cite journal | vauthors = Daw Z, Padmore R, Neurath D, Cober N, Tokessy M, Desjardins D, Olberg B, Tinmouth A, Giulivi A | title = Hemolytic transfusion reactions after administration of intravenous immune (gamma) globulin: a case series analysis | journal = Transfusion | volume = 48 | issue = 8 | pages = 1598–1601 | date = August 2008 | pmid = 18466176 | doi = 10.1111/j.1537-2995.2008.01721.x | s2cid = 6010463 }}</ref>

In the case of less serious side effects, a patient's infusion rate can be adjusted downwards until the side effects become tolerable, while in the case of more serious side effects, emergency medical attention should be sought.<ref name=scriptinfo>{{cite web | title=Hyqvia (immune globulin 10 percent- human with recombinant human hyaluronidase) kit | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7ca2c26f-4be2-48cd-be5b-486e350654ba | access-date=1 May 2020 | archive-date=5 August 2020 | archive-url=https://web.archive.org/web/20200805002533/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7ca2c26f-4be2-48cd-be5b-486e350654ba | url-status=live }}</ref>

Immunoglobulin therapy also interferes with the ability of the body to produce a normal immune response to an attenuated live virus vaccine for up to a year,<ref name=dyna/> can result in falsely elevated blood glucose levels,<ref name=dyna/> and can interfere with many of the IgG-based assays often used to diagnose a patient with a particular infection.<ref name=citm>{{cite journal| vauthors = Lichtiger B | journal =  Current Issues in Transfusion Medicine | date = April 1994 | volume = 3 | pages = 1–7 |title= Laboratory Serologic Problems Associated with Administration of Intravenous IgG |url= http://www3.mdanderson.org/~citm/H-94-04.html|publisher=The University of Texas M. D. Anderson Cancer Center|access-date=23 November 2015|url-status=dead|archive-url=https://web.archive.org/web/20160305122623/http://www3.mdanderson.org/~citm/H-94-04.html|archive-date=5 March 2016}}</ref>

==Routes of administration==
===1950s – intramuscular===
After immunoglobulin therapy's discovery in 1952, weekly [[Biology:Intramuscular injection|intramuscular injection]]s of immunoglobulin (IMIg) were the norm until [[Chemistry:Intravenous therapy|intravenous]] formulations (IVIg) began to be introduced in the 1980s.<ref name=scig/> During the mid and late 1950s,{{vague|date=December 2023}} one-time IMIg injections were a common public health response to outbreaks of [[Medicine:Polio|polio]] before the widespread availability of vaccines. Intramuscular injections were extremely poorly tolerated due to their extreme pain and poor efficacy – rarely could intramuscular injections alone raise plasma immunoglobulin levels enough to make a clinically meaningful difference.<ref name=scig/>

=== 1980s – intravenous ===
Intravenous formulations began to be approved in the 1980s, which represented a significant improvement over intramuscular injections, as they allowed for a sufficient amount of immunoglobulin to be injected to reach clinical efficacy, although they still had a fairly high rate of adverse effects (though the addition of stabilizing agents reduced this further).<ref name=scig/>

=== 1990s – subcutaneous ===
The first description of a [[Medicine:Subcutaneous injection|subcutaneous]] route of administration for immunoglobulin therapy dates back to 1980,<ref>{{cite journal | vauthors = Misbah S, Sturzenegger MH, Borte M, Shapiro RS, Wasserman RL, Berger M, Ochs HD | title = Subcutaneous immunoglobulin: opportunities and outlook | journal = Clinical and Experimental Immunology | volume = 158 | issue = Suppl 1 | pages = 51–59 | date = December 2009 | pmid = 19883424 | pmc = 2801034 | doi = 10.1111/j.1365-2249.2009.04027.x | doi-access = free | title-link = doi }}</ref> but for many years subcutaneous administration was considered to be a secondary choice, only to be considered when peripheral venous access was no longer possible or tolerable.<ref name=scig/>

During the late 1980s and early 1990s,{{vague|date=December 2023}} it became obvious that for at least a subset of patients the systemic adverse events associated with intravenous therapy were still not easily tolerable, and more doctors began to experiment with subcutaneous immunoglobulin administration, culminating in an ''ad hoc'' clinical trial in Sweden of 3000 subcutaneous injections administered to 25 adults (most of whom had previously experienced systemic adverse effects with IMIg or IVIg), where no infusion in the ''ad hoc'' trial resulted in a severe systemic adverse reaction, and most subcutaneous injections were able to be administered in non-hospital settings, allowing for considerably more freedom for the people involved.<ref name=scig/>

In the later 1990s, large-scale trials began in Europe to test the feasibility of subcutaneous immunoglobulin administration, although it was not until 2006 that the first subcutaneous-specific preparation of immunoglobulin was approved by a major regulatory agency (Vivaglobin, which was voluntarily discontinued in 2011).<ref name=scig/><ref name=vivadisc>{{cite web| vauthors = Powell L |title=Re: A Message from CSL Behring to Current Vivaglobin Patients in the United States|url=http://primaryimmune.org/wp-content/uploads/2011/05/Vivaglobin_Letter.pdf|website=Primary Immune Foundation|access-date=24 November 2015|url-status=live|archive-url=https://web.archive.org/web/20151222155226/http://primaryimmune.org/wp-content/uploads/2011/05/Vivaglobin_Letter.pdf|archive-date=22 December 2015}}</ref> A number of other trade names of subcutaneous immunoglobulin have since been approved, although some small-scale studies have indicated that a particular cohort of patients with [[Medicine:Common variable immunodeficiency|common variable immunodeficiency]] (CVID) may develop intolerable side effects with subcutaneous immunoglobulin (SCIg) that they do not with intravenous immunoglobulin (IVIg).<ref name=scig/>

Although intravenous was the preferred route for immunoglobulin therapy for many years, in 2006, the US [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA) approved the first preparation of immunoglobulin that was designed exclusively for subcutaneous use.<ref name=scig>{{cite journal | vauthors = Skoda-Smith S, Torgerson TR, Ochs HD | title = Subcutaneous immunoglobulin replacement therapy in the treatment of patients with primary immunodeficiency disease | journal = Therapeutics and Clinical Risk Management | volume = 6 | pages = 1–10 | date = February 2010 | pmid = 20169031 | pmc = 2817783 | doi = 10.2147/tcrm.s4353 | doi-access = free }}</ref>

== Mechanism of action ==
The precise mechanism by which immunoglobulin therapy suppresses harmful [[Medicine:Inflammation|inflammation]] is likely multifactorial.<ref>{{cite journal |author=Lee Martin N, Butani Lavjay |title=Intravenous Immunoglobulin (IVIG) in Rheumatologic Diseases: A Review of its Mechanism of Action |journal=Current Rheumatology Reviews |volume=1 |issue=3 |pages=289–93 |date= 2005|doi=10.2174/157339705774612355 }}</ref> For example, it has been reported that immunoglobulin therapy can block [[Biology:Fas receptor|Fas]]-mediated cell death.<ref>{{cite journal | vauthors = Viard I, Wehrli P, Bullani R, Schneider P, Holler N, Salomon D, Hunziker T, Saurat JH, Tschopp J, French LE | title = Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin | journal = Science | volume = 282 | issue = 5388 | pages = 490–493 | date = October 1998 | pmid = 9774279 | doi = 10.1126/science.282.5388.490 | bibcode = 1998Sci...282..490V }}</ref>

Perhaps a more popular theory is that the immunosuppressive effects of immunoglobulin therapy are mediated through IgG's [[Biology:Fragment crystallizable region|Fc glycosylation]]. By binding to receptors on antigen presenting cells, IVIG can increase the expression of the inhibitory [[Biology:Fc receptor|Fc receptor]], FcgRIIB, and shorten the half-life of auto-reactive antibodies.<ref name = "immune_glycan"/><ref>{{cite journal|author=Gern JE|date=August 2002|title=Antiinflammatory Activity of IVIG Mediated through the Inhibitory FC Receptor|url=https://pediatrics.aappublications.org/content/110/Supplement_2/467.1.full|url-status=live|journal=Pediatrics|volume=110|issue=2|pages=467–68|doi=10.1542/peds.110.S2.467a|archive-url=https://web.archive.org/web/20080611051106/http://pediatrics.aappublications.org/cgi/content/full/110/2/S1/467-b|archive-date=11 June 2008}}</ref><ref>{{cite journal | vauthors = Nimmerjahn F, Ravetch JV | title = The antiinflammatory activity of IgG: the intravenous IgG paradox | journal = The Journal of Experimental Medicine | volume = 204 | issue = 1 | pages = 11–15 | date = January 2007 | pmid = 17227911 | pmc = 2118416 | doi = 10.1084/jem.20061788 }}</ref> The ability of immunoglobulin therapy to suppress pathogenic immune responses by this mechanism is dependent on the presence of a sialylated glycan at position CH2-84.4 of IgG.<ref name = "immune_glycan"/> Specifically, de-sialylated preparations of immunoglobulin lose their therapeutic activity and the anti-inflammatory effects of IVIG can be recapitulated by administration of recombinant sialylated IgG1 Fc.<ref name = "immune_glycan">{{cite journal | vauthors = Maverakis E, Kim K, Shimoda M, Gershwin ME, Patel F, Wilken R, Raychaudhuri S, Ruhaak LR, Lebrilla CB | title = Glycans in the immune system and The Altered Glycan Theory of Autoimmunity: a critical review | journal = Journal of Autoimmunity | volume = 57 | issue = 6 | pages = 1–13 | date = February 2015 | pmid = 25578468 | pmc = 4340844 | doi = 10.1016/j.jaut.2014.12.002 }}</ref>

Sialylated-Fc-dependent mechanism was not reproduced in other experimental models suggesting that this mechanism is functional under a particular disease or experimental settings.<ref>{{cite journal | vauthors = Galeotti C, Kaveri SV, Bayry J | title = IVIG-mediated effector functions in autoimmune and inflammatory diseases | journal = International Immunology | volume = 29 | issue = 11 | pages = 491–498 | date = December 2017 | pmid = 28666326 | doi = 10.1093/intimm/dxx039 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Maddur MS, Kaveri SV, Bayry J | title = Circulating Normal IgG as Stimulator of Regulatory T Cells: Lessons from Intravenous Immunoglobulin | journal = Trends in Immunology | volume = 38 | issue = 11 | pages = 789–792 | date = November 2017 | pmid = 28916232 | doi = 10.1016/j.it.2017.08.008 | url = https://hal.sorbonne-universite.fr/hal-01630293/file/Trends%20Immunol%20Forum%20BAYRY_R1_JD_JB.pdf | access-date = 12 January 2022 | archive-date = 1 February 2022 | archive-url = https://web.archive.org/web/20220201070005/https://hal.sorbonne-universite.fr/hal-01630293/file/Trends%20Immunol%20Forum%20BAYRY_R1_JD_JB.pdf | url-status = live }}</ref><ref>{{cite journal | vauthors = Othy S, Topçu S, Saha C, Kothapalli P, Lacroix-Desmazes S, Käsermann F, Miescher S, Bayry J, Kaveri SV | title = Sialylation may be dispensable for reciprocal modulation of helper T cells by intravenous immunoglobulin | journal = European Journal of Immunology | volume = 44 | issue = 7 | pages = 2059–2063 | date = July 2014 | pmid = 24700174 | doi = 10.1002/eji.201444440 | s2cid = 29700587 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Campbell IK, Miescher S, Branch DR, Mott PJ, Lazarus AH, Han D, Maraskovsky E, Zuercher AW, Neschadim A, Leontyev D, McKenzie BS, Käsermann F | title = Therapeutic effect of IVIG on inflammatory arthritis in mice is dependent on the Fc portion and independent of sialylation or basophils | journal = Journal of Immunology | volume = 192 | issue = 11 | pages = 5031–5038 | date = June 2014 | pmid = 24760152 | doi = 10.4049/jimmunol.1301611| pmc=4025610 }}</ref> On the other hand, several other mechanisms of action and the actual primary targets of immunoglobulin therapy have been reported. In particular, F(ab')2-dependent action of immunoglobulin to inhibit activation of human dendritic cells,<ref>{{cite journal | vauthors = Bayry J, Lacroix-Desmazes S, Carbonneil C, Misra N, Donkova V, Pashov A, Chevailler A, Mouthon L, Weill B, Bruneval P, Kazatchkine MD, Kaveri SV | title = Inhibition of maturation and function of dendritic cells by intravenous immunoglobulin | journal = Blood | volume = 101 | issue = 2 | pages = 758–765 | date = January 2003 | pmid = 12393386 | doi = 10.1182/blood-2002-05-1447 }}</ref> induction of autophagy,<ref>{{cite journal | vauthors = Das M, Karnam A, Stephen-Victor E, Gilardin L, Bhatt B, Kumar Sharma V, Rambabu N, Patil V, Lecerf M, Käsermann F, Bruneval P, Narayanaswamy Balaji K, Benveniste O, Kaveri SV, Bayry J | title = Intravenous immunoglobulin mediates anti-inflammatory effects in peripheral blood mononuclear cells by inducing autophagy | journal = Cell Death & Disease | volume = 11 | issue = 1 | pages = 50 | date = January 2020 | pmid = 31974400 | doi = 10.1038/s41419-020-2249-y |pmc=6978335 }}</ref> induction of COX-2-dependent PGE-2 in human dendritic cells leading to expansion of regulatory T cells,<ref>{{cite journal | vauthors = Trinath J, Hegde P, Sharma M, Maddur MS, Rabin M, Vallat JM, Magy L, Balaji KN, Kaveri SV, Bayry J | title = Intravenous immunoglobulin expands regulatory T cells via induction of cyclooxygenase-2-dependent prostaglandin E2 in human dendritic cells | journal = Blood | volume = 122 | issue = 8 | pages = 1419–1427 | date = August 2013 | pmid = 23847198 | doi = 10.1182/blood-2012-11-468264 | doi-access = free }}</ref> inhibition of pathogenic Th17 responses,<ref>{{cite journal | vauthors = Maddur MS, Vani J, Hegde P, Lacroix-Desmazes S, Kaveri SV, Bayry J | title = Inhibition of differentiation, amplification, and function of human TH17 cells by intravenous immunoglobulin | journal = The Journal of Allergy and Clinical Immunology | volume = 127 | issue = 3 | date = March 2011 | pages = 823–30.e1–7 | pmid = 21281961 | doi = 10.1016/j.jaci.2010.12.1102 | s2cid = 2323773 }}</ref> and induction of human basophil activation and IL-4 induction via anti-IgE autoantibodies.<ref>{{cite journal | vauthors = Galeotti C, Stephen-Victor E, Karnam A, Das M, Gilardin L, Maddur MS, Wymann S, Vonarburg C, Chevailler A, Dimitrov JD, Benveniste O, Bruhns P, Kaveri SV, Bayry J | title = Intravenous immunoglobulin induces IL-4 in human basophils by signaling through surface-bound IgE | journal = The Journal of Allergy and Clinical Immunology | volume = 144 | issue = 2 | pages = 524–535.e8 | date = August 2019 | pmid = 30529242 | doi = 10.1016/j.jaci.2018.10.064 | s2cid = 54476352 | url = https://hal.sorbonne-universite.fr/hal-02284256/file/Galeotti%20et%20al.%20-%202019%20-%20Intravenous%20immunoglobulin%20induces%20IL-4%20in%20human%20b.pdf | access-date = 8 July 2022 | archive-date = 7 March 2020 | archive-url = https://web.archive.org/web/20200307031139/https://hal.sorbonne-universite.fr/hal-02284256/file/Galeotti%20et%20al.%20-%202019%20-%20Intravenous%20immunoglobulin%20induces%20IL-4%20in%20human%20b.pdf | url-status = live }}</ref><ref>{{cite journal | vauthors = Galeotti C, Karnam A, Dimitrov JD, Chevailler A, Kaveri SV, Bayry J | title = Anti-IgE IgG autoantibodies isolated from therapeutic normal IgG intravenous immunoglobulin induce basophil activation | journal = Cellular & Molecular Immunology | volume = 17 | issue = 4 | pages = 426–429 | date = April 2020 | pmid = 31797906 | doi = 10.1038/s41423-019-0334-x|pmc=7109030 }}</ref> Some believe that immunoglobulin therapy may work via a multi-step model where the injected immunoglobulin first forms a type of [[Biology:Immune complex|immune complex]] in the patient.<ref>{{cite journal | vauthors = Clynes R | title = Immune complexes as therapy for autoimmunity | journal = The Journal of Clinical Investigation | volume = 115 | issue = 1 | pages = 25–27 | date = January 2005 | pmid = 15630438 | pmc = 539209 | doi = 10.1172/JCI23994 }}</ref> Once these immune complexes are formed, they can interact with Fc receptors on dendritic cells,<ref>{{cite journal | vauthors = Siragam V, Crow AR, Brinc D, Song S, Freedman J, Lazarus AH | title = Intravenous immunoglobulin ameliorates ITP via activating Fc gamma receptors on dendritic cells | journal = Nature Medicine | volume = 12 | issue = 6 | pages = 688–692 | date = June 2006 | pmid = 16715090 | doi = 10.1038/nm1416 | s2cid = 40468774 }}</ref> which then mediate anti-inflammatory effects helping to reduce the severity of the autoimmune disease or inflammatory state.

Other proposed mechanisms include the possibility that donor antibodies may bind directly with the abnormal host antibodies, stimulating their removal; the possibility that IgG stimulates the host's [[Biology:Complement system|complement system]], leading to enhanced removal of all antibodies, including the harmful ones; and the ability of immunoglobulin to block the antibody receptors on immune cells ([[Biology:Macrophage|macrophage]]s), leading to decreased damage by these cells, or regulation of macrophage [[Biology:Phagocytosis|phagocytosis]]. Indeed, it is becoming more clear that immunoglobulin can bind to a number of membrane receptors on T cells, B cells, and monocytes that are pertinent to autoreactivity and induction of tolerance to self.<ref name = "immune_glycan"/><ref>{{cite journal | vauthors = Bayry J, Thirion M, Misra N, Thorenoor N, Delignat S, Lacroix-Desmazes S, Bellon B, Kaveri S, Kazatchkine MD | title = Mechanisms of action of intravenous immunoglobulin in autoimmune and inflammatory diseases | journal = Neurological Sciences | volume = 24 | issue = Suppl 4 | pages = S217–S221 | date = October 2003 | pmid = 14598046 | doi = 10.1007/s10072-003-0081-7 | s2cid = 5945755 }}</ref>

A report stated that immunoglobulin application to activated T cells leads to their decreased ability to engage [[Biology:Microglia|microglia]]. As a result of immunoglobulin treatment of T cells, the findings showed reduced levels of tumor necrosis factor-alpha and interleukin-10 in T cell-microglia co-culture. The results add to the understanding of how immunoglobulin may affect inflammation of the central nervous system in autoimmune inflammatory diseases.<ref>{{cite journal | vauthors = Janke AD, Yong VW | title = Impact of IVIg on the interaction between activated T cells and microglia | journal = Neurological Research | volume = 28 | issue = 3 | pages = 270–274 | date = April 2006 | pmid = 16687052 | doi = 10.1179/016164106X98143 | s2cid = 18239570 }}</ref>

==Hyperimmune globulin==
'''Hyperimmune globulins''' are a class of immunoglobulins prepared in a similar way as for ''normal human immunoglobulin'', except that the donor has high titers of [[Biology:Antibody|antibody]] against a specific organism or [[Biology:Antigen|antigen]] in their [[Biology:Blood plasma|plasma]]. Some agents against which hyperimmune globulins are available include [[Medicine:Hepatitis B|hepatitis B]], [[Medicine:Rabies|rabies]], [[Medicine:Tetanus|tetanus]] toxin, varicella-zoster, etc. Administration of hyperimmune globulin provides [[Biology:Passive immunity|"passive" immunity]] to the patient against an agent. This is in contrast to [[Biology:Vaccine|vaccine]]s that provide "active" immunity. However, vaccines take much longer to achieve that purpose while hyperimmune globulin provides instant "passive" short-lived immunity. Hyperimmune globulin may have serious [[Medicine:Side effect|side effect]]s, thus usage is taken very seriously.{{citation needed|date=December 2021}}

Hyperimmune [[Biology:Serum (blood)|serum]] and [[Biology:Blood plasma|plasma]] contain high amounts of an antibody, as a consequence of disease convalescence<ref>{{cite journal | vauthors = Mair-Jenkins J, Saavedra-Campos M, Baillie JK, Cleary P, Khaw FM, Lim WS, Makki S, Rooney KD, Nguyen-Van-Tam JS, Beck CR | title = The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis | journal = The Journal of Infectious Diseases | volume = 211 | issue = 1 | pages = 80–90 | date = January 2015 | pmid = 25030060 | pmc = 4264590 | doi = 10.1093/infdis/jiu396 }}</ref> or of repeated immunization.<ref>{{cite web |title=Antivenoms |url=https://www.who.int/teams/control-of-neglected-tropical-diseases/snakebite-envenoming/antivenoms |access-date=2023-05-23 |website=www.who.int |language=en}}</ref> Hyperimmune plasma is used in veterinary medicine,<ref>{{cite web |date=2021-05-20 |title=What is Hyperimmunized Plasma? |url=https://plasvaccusa.com/what-is-hyperimmunized-plasma/ |access-date=2023-05-23 |website=Plasvacc USA |language=en-US}}</ref> and hyperimmune plasma derivatives are used to treat snakebite.<ref>{{cite journal | vauthors = Dias da Silva W, De Andrade SA, Megale ÂA, De Souza DA, Sant'Anna OA, Magnoli FC, Guidolin FR, Godoi KS, Saladini LY, Spencer PJ, Portaro FC | title = Antibodies as Snakebite Antivenoms: Past and Future | journal = Toxins | volume = 14 | issue = 9 | pages = 606 | date = September 2022 | pmid = 36136544 | pmc = 9503307 | doi = 10.3390/toxins14090606 | doi-access = free }}</ref> It has been hypothesized that hyperimmune serum may be an effective therapy for persons infected with the [[Biology:Ebola virus|Ebola virus]].<ref>{{cite journal | vauthors = Kudoyarova-Zubavichene NM, Sergeyev NN, Chepurnov AA, Netesov SV | title = Preparation and use of hyperimmune serum for prophylaxis and therapy of Ebola virus infections | journal = The Journal of Infectious Diseases | volume = 179 | issue = Suppl 1 | pages = S218–S223 | date = February 1999 | pmid = 9988187 | doi = 10.1086/514294 | title-link = doi | doi-access = free }}</ref>

==Society and culture==
=== Economics ===
In the United Kingdom a dose cost the NHS between {{GBP}}11.20 and {{GBP}}1,200.00 depending on the type and amount.<ref name=BNF69/> In the United States, antivenoms may cost thousands of dollars per dose because of markups that occur after manufacturing.<ref>{{cite news | vauthors = Ingraham C |date=2021-11-25 |title=The crazy reason it costs $14,000 to treat a snakebite with $14 medicine |language=en-US |newspaper=Washington Post |url=https://www.washingtonpost.com/news/wonk/wp/2015/09/09/the-crazy-reason-it-costs-14000-to-treat-a-snakebite-with-14-medicine/ |access-date=2023-05-23 |issn=0190-8286}}</ref>

===Brand names===
As [[Medicine:Biopharmaceutical|biologicals]], various trade names of immunoglobulin products are ''not'' necessarily interchangeable, and care must be exercised when changing between them.<ref name=aaaiguiding>{{cite web|title=Eight Guiding Principles for Effective Use of IVIG for Patients with Primary Immunodeficiency|url=http://www.aaaai.org/Aaaai/media/MediaLibrary/PDF%20Documents/Practice%20Resources/IVIG-guiding-principles.pdf|publisher=American Association of Allergists and Immunologists|access-date=23 November 2015|url-status=live|archive-url=https://web.archive.org/web/20160305025940/https://www.aaaai.org/Aaaai/media/MediaLibrary/PDF%20Documents/Practice%20Resources/IVIG-guiding-principles.pdf|archive-date=5 March 2016}}</ref> Trade names of intravenous immunoglobulin formulations include Flebogamma, Gamunex, Privigen, Octagam and Gammagard, while trade names of subcutaneous formulations include Cutaquig, Cuvitru, HyQvia, Hizentra,<ref name="Hizentra EPAR" /><ref>{{cite web | title=Hizentra | website=U.S. [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA) | date=15 March 2018 | url=https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/hizentra | access-date=3 May 2020 | archive-date=1 April 2020 | archive-url=https://web.archive.org/web/20200401234108/https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/hizentra | url-status=live }}</ref><ref>{{cite report|url=https://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM601862.pdf|title=Summary Basis for Regulatory Action – Hizentra| vauthors = Pierce LR |date=14 March 2018|publisher=U.S. [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA)|access-date=20 March 2018|others=Review Office Signatory Authority Tejashri Purohit-Sheth|archive-date=20 March 2018|archive-url=https://web.archive.org/web/20180320232958/https://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM601862.pdf|url-status=live}}</ref> Gamunex-C, and Gammaked.<ref name=brands>{{cite journal| vauthors = Berman K |title=SCIG: New Therapeutic Uses Beyond PI?|journal=IG Living|issue=February–March 2015|pages=28–32|url=http://www.igliving.com/magazine/articles/IGL_2015-02_AR_SCIG-New-Therapeutic-Uses-Beyond-PI.pdf|access-date=23 November 2015|url-status=live|archive-url=https://web.archive.org/web/20151027084644/http://www.igliving.com/magazine/articles/IGL_2015-02_AR_SCIG-New-Therapeutic-Uses-Beyond-PI.pdf|archive-date=27 October 2015}}</ref>

=== Supply issues ===

The United States is one of a handful of countries that allow plasma donors to be paid, meaning that the US supplies much of the plasma-derived medicinal products (including immunoglobulin) used across the world, including more than 50% of the European Union's supply.<ref name=euc/> The Council of Europe has officially endorsed the idea of not paying for plasma donations for both ethical reasons and reasons of safety, but studies have found that relying on entirely voluntary plasma donation leads to shortages of immunoglobulin and forces member countries to import immunoglobulin from countries that do compensate donors.<ref name=euc>{{cite web|title=An EU-wide overview of the market of blood, blood components and plasma derivatives focusing on their availability for patients Creative Ceutical Report, revised by the Commission to include stakeholders' comments|url=http://ec.europa.eu/health/blood_tissues_organs/docs/20150408_cc_report_en.pdf|publisher=Creative Ceutical & EU commission|access-date=7 December 2015|url-status=live|archive-url=https://web.archive.org/web/20151222154843/http://ec.europa.eu/health/blood_tissues_organs/docs/20150408_cc_report_en.pdf|archive-date=22 December 2015}}</ref>

In Australia, blood donation is voluntary and therefore to cope with increasing demand and to reduce the shortages of locally produced immunoglobulin, several programs have been undertaken including adopting plasma for first time blood donors, better processes for donation, plasma donor centres and encouraging current blood donors to consider plasma only donation.<ref>{{cite web |title=transfusion.com.au |url=https://transfusion.com.au/bsib_april2017_5 |website=transfusion.com.au |access-date=14 November 2019 |language=en |archive-date=4 September 2019 |archive-url=https://web.archive.org/web/20190904062618/https://transfusion.com.au/bsib_april2017_5 |url-status=live }}</ref>

==Research==
Experimental results from a small [[Engineering:Clinical trial|clinical trial]] in humans suggested protection against the progression of [[Medicine:Alzheimer's disease|Alzheimer's disease]], but no such benefit was found in a subsequent phase III clinical trial.<ref name="NYT2012">{{cite web|url=https://www.nytimes.com/2012/07/18/business/study-shows-drug-may-help-alzheimers-patients.html|title=Small Trial Hints Drug Can Slow Alzheimer's|author=Andrew Pollack|date=17 July 2012|work=New York Times|url-access=registration|url-status=live|archive-url=https://web.archive.org/web/20120719123729/http://www.nytimes.com/2012/07/18/business/study-shows-drug-may-help-alzheimers-patients.html|archive-date=19 July 2012|access-date=19 July 2012}}</ref><ref>{{cite web|url=http://www.cbsnews.com/8301-504763_162-57474035-10391704/experimental-alzheimers-drug-gammagard-may-stall-memory-decline-small-study-suggests/|title=Experimental Alzheimer's drug Gammagard may stall memory decline, small study suggests|publisher=CBS News|date=17 July 2012|access-date=19 July 2012|url-status=live|archive-url=https://web.archive.org/web/20120719063457/http://www.cbsnews.com/8301-504763_162-57474035-10391704/experimental-alzheimers-drug-gammagard-may-stall-memory-decline-small-study-suggests/|archive-date=19 July 2012}}</ref><ref>{{cite web|url=http://www.genengnews.com/gen-news-highlights/another-alzheimer-s-drug-fails-phase-iii-trial/81248326/|archive-url=https://web.archive.org/web/20130607013806/http://www.genengnews.com/gen-news-highlights/another-alzheimer-s-drug-fails-phase-iii-trial/81248326|url-status=dead|title=Another Alzheimer's Drug Fails Phase III Trial|archive-date=7 June 2013}}</ref> In May 2020, the US approved a phase three clinical trial on the efficacy and safety of high-concentration intravenous immune globulin therapy in severe [[Medicine:COVID-19|COVID-19]].<ref>{{cite web|title=FDA Approves Octapharma USA Investigational New Drug Application for Severe COVID-19 Patients|url=https://www.businesswire.com/news/home/20200520005133/en/FDA-Approves-Octapharma-USA-Investigational-New-Drug|date=20 May 2020|website=www.businesswire.com|language=en|access-date=28 May 2020|archive-date=21 June 2020|archive-url=https://web.archive.org/web/20200621081731/https://www.businesswire.com/news/home/20200520005133/en/FDA-Approves-Octapharma-USA-Investigational-New-Drug|url-status=live}}</ref> Efficacy of heterologous immunoglobulin derivatives has been demonstrated in clinical trials of antivenoms for scorpion sting<ref>{{cite journal | vauthors = Boyer LV, Theodorou AA, Berg RA, Mallie J, Chávez-Méndez A, García-Ubbelohde W, Hardiman S, Alagón A | title = Antivenom for critically ill children with neurotoxicity from scorpion stings | journal = The New England Journal of Medicine | volume = 360 | issue = 20 | pages = 2090–2098 | date = May 2009 | pmid = 19439743 | doi = 10.1056/NEJMoa0808455 | doi-access = free }}</ref> and for snakebite.<ref>{{cite journal | vauthors = Williams DJ, Habib AG, Warrell DA | title = Clinical studies of the effectiveness and safety of antivenoms | journal = Toxicon | volume = 150 | pages = 1–10 | date = August 2018 | pmid = 29746978 | doi = 10.1016/j.toxicon.2018.05.001 | s2cid = 13665273 }}</ref>

== References ==
{{reflist}}

{{Medicine}}
{{Major drug groups}}
{{Immune sera and immunoglobulins}}

[[Category:Medical treatments]]
[[Category:Transfusion medicine]]
[[Category:World Health Organization essential medicines]]
[[Category:Wikipedia medicine articles ready to translate]]

{{Sourceattribution|Immunoglobulin therapy}}