View source for Medicine:Complement deficiency

{{Infobox medical condition (new)
| name            = Complement deficiency
| image           = Complement pathway.svg
| caption         = Complement pathway (normal)
| pronounce       =
| field           =
| synonyms        =
| symptoms        = Recurring infection, rheumatic disease<ref name=osk/>
| complications   =
| onset           =
| duration        =
| types           =
| causes          = Can be inherited or acquired<ref name=pat/>
| risks           =
| diagnosis       = CH50 measurement, Plasma level<ref name=scape/>
| differential    =
| prevention      =
| treatment       = Immunosuppressive therapy<ref name=pat/>
| medication      =
| prognosis       =
| frequency       =
| deaths          =
}}
'''Complement deficiency''' is an immunodeficiency of absent or suboptimal functioning of one of the [[Biology:Complement system|complement system]] proteins.<ref name="GorbachBartlett2004">{{cite book |first1=Jerry A. |last1=Winkelstein |chapter=The Complement System |pages=8–13 |editor1-first=Sherwood L. |editor1-last=Gorbach |editor2-first=John G. |editor2-last=Bartlett |editor3-first=Neil R. |editor3-last=Blacklow |title=Infectious Diseases |date=2004 |publisher=Lippincott Williams & Wilkins |isbn=978-0-7817-3371-7}}</ref> Because of redundancies in the [[Biology:Immune system|immune system]], many complement disorders are never diagnosed. Some studies estimate that less than 10% are identified.<ref>{{cite journal |doi=10.1016/j.molimm.2005.06.025 |pmid=16026838 |title=Complement deficiency and disease: An update |journal=Molecular Immunology |volume=43 |issue=1–2 |pages=78–85 |year=2006 |last1=Sjöholm |first1=A.G. |last2=Jönsson |first2=G. |last3=Braconier |first3=J.H. |last4=Sturfelt |first4=G. |last5=Truedsson |first5=L. }}{{Subscription or libraries|sentence|via=[[ScienceDirect]]}}</ref> ''Hypocomplementemia'' may be used more generally to refer to decreased complement levels,<ref>{{cite book|editor-first=Larry W. |editor-last=Moreland|title=Rheumatology and Immunology Therapy: A to Z Essentials|date=2004|publisher=Springer|location=Berlin|isbn=9783540206255|page=425|url= https://books.google.com/books?id=GiR493YLsgsC&q=hypocomplementemia+definition&pg=PA425|access-date=30 August 2016|language=en}}</ref> while ''secondary complement disorder'' means decreased complement levels that are not directly due to a genetic cause but secondary to another medical condition.<ref name="emed">{{EMedicine|article|136368|Complement-Related Disorders}}</ref>

==Signs and symptoms==
The following symptoms (signs) are consistent with complement deficiency in general:<ref name="osk">{{cite book|last1=Winkelstein|first1=Jerry A.|chapter=Complement Deficiencies|editor1-last=Crocetti|editor1-first=Michael|editor2-last=Barone|editor2-first=Michael A.|title=Oski's Essential Pediatrics|date=2004|publisher=Lippincott Williams & Wilkins|location=Philadelphia|isbn=9780781737708|page=670|edition=2nd|chapter-url=https://books.google.com/books?id=I3Kh1cNJxyUC&q=complement+deficiency&pg=PA670|access-date=21 September 2016|language=en}}</ref><ref name=scape/><ref>{{cite journal|last1=Pettigrew|first1=H. David|last2=Teuber|first2=Suzanne S.|last3=Gershwin|first3=M. Eric|title=Clinical Significance of Complement Deficiencies|journal=Annals of the New York Academy of Sciences|date=September 2009|volume=1173|issue=1|pages=108–123|doi=10.1111/j.1749-6632.2009.04633.x|pmid=19758139|language=en|issn=1749-6632|bibcode=2009NYASA1173..108P|doi-access=free}}</ref>
{{columns-list|colwidth=30em|
* Recurring [[Medicine:Infection|infection]]
* Auto-immune disorders
* [[Medicine:Glomerulonephritis|Glomerulonephritis]]
* [[Biology:Joint|Joint]] problems (manifestation)
* [[Medicine:Lung|Lung]] function (MBL variant alleles)
* [[Medicine:Angioedema|Angioedema]]
* [[Medicine:Dermatomyositis|Dermatomyositis]]
* [[Medicine:Vasculitis|Vasculitis]]
* Anaphylactoid purpura
}}

===Complications===
[[File:Neisseria-meningitidis-Differentially-Controls-Host-Cell-Motility-through-PilC1-and-PilC2-pone.0006834.s003.ogv|thumb|230 px|Neisseria, a possible complication]]

Vaccinations for encapsulated organisms (e.g., ''[[Biology:Neisseria meningitidis|Neisseria meningitidis]]'' and ''[[Biology:Streptococcus pneumoniae|Streptococcus pneumoniae]]'')  is crucial for preventing infections in complement deficiencies.{{medical citation needed|date=September 2016}} Among the possible complications are the following:
* Deficiencies of the terminal complement components increases susceptibility to infections by ''[[Biology:Neisseria|Neisseria]]''.<ref>{{cite book |last1=Aghamohammadi |first1=Asghar |last2=Rezaei |first2=Nima |title=Clinical Cases in Primary Immunodeficiency Diseases: A Problem-Solving Approach |date=13 December 2012 |publisher=Springer Science & Business Media |isbn=978-3-642-31785-9 |page=334 |url=https://books.google.com/books?id=IftYOIDjQbcC&q=terminal+complement+components+Neisseria.&pg=PA334 |access-date=30 January 2022 |language=en}}</ref>

==Causes==
The cause of complement deficiency is genetics (though cases of an acquired nature do exist post infection). The majority of complement deficiencies are inherited as autosomal recessive conditions, while [[Medicine:Properdin deficiency|properdin deficiency]] occurs through X-linked inheritance. MBL deficiency can be inherited by either manner.<ref name=pat/>

===Inherited===
* [[Medicine:Properdin deficiency|Properdin deficiency]] is an X-linked<ref>{{cite web|title=OMIM Entry - # 312060 - PROPERDIN DEFICIENCY, X-LINKED; CFPD|url=http://omim.org/entry/312060|website=omim.org|access-date=21 September 2016}}</ref> disorder that also causes susceptibility to ''[[Biology:Neisseria|Neisseria]]'' infections.<ref name=pat/>
* C1-inhibitor deficiency or [[Medicine:Hereditary angioedema|hereditary angioedema]] will have low C4 with normal C1 levels.<ref>{{cite journal|last1=Gower|first1=Richard G|last2=Busse|first2=Paula J|last3=Aygören-Pürsün|first3=Emel|last4=Barakat|first4=Amin J|last5=Caballero|first5=Teresa|last6=Davis-Lorton|first6=Mark|last7=Farkas|first7=Henriette|last8=Hurewitz|first8=David S|last9=Jacobs|first9=Joshua S|last10=Johnston|first10=Douglas T|last11=Lumry|first11=William|last12=Maurer|first12=Marcus|title=Hereditary Angioedema Caused By C1-Esterase Inhibitor Deficiency: A Literature-Based Analysis and Clinical Commentary on Prophylaxis Treatment Strategies|journal=The World Allergy Organization Journal|date=15 February 2011|volume=4|issue=Suppl 2|pages=S9–S21|doi=10.1097/1939-4551-4-S2-S9|pmc=3666183|issn=1939-4551|pmid=23283143}}</ref>

===Acquired===
Acquired hypocomplementemia may occur in the setting of [[Medicine:Osteomyelitis|bone infections (osteomyelitis)]], [[Medicine:Endocarditis|infection of the lining of the heart (endocarditis)]], and [[Medicine:Cryoglobulinemia|cryoglobulinemia]]. [[Medicine:Systemic lupus erythematosus|Systemic lupus erythematosus]] is associated with low C3 and [[Medicine:Complement component 4|C4]].<ref>{{cite web|title=Systemic Lupus Erythematosus. Lupus treatment; information {{!}} Patient|url=http://patient.info/doctor/systemic-lupus-erythematosus-pro|website=Patient|access-date=21 September 2016}}</ref> Membranoproliferative glomerulonephritis usually has low C3.<ref>{{cite web|title=Membranoproliferative Glomerulonephritis: Background, Pathophysiology, Etiology|url=http://emedicine.medscape.com/article/240056-overview|website=Medscape|access-date=21 September 2016}}</ref>

==Mechanism==
[[File:Genetic Risk of Schizophrenia Summary Figure.png|thumb|right|500 px|Model of common structural genes and their possible contribution to the development of schizophrenia (as defined in the Sekar ''et al''. article)]]
The mechanism of complement deficiency consists of:
* '''C2''': In regard to C2 deficiency, about 5 different [[Biology:Mutation|mutation]]s in the ''C2'' [[Biology:Gene|gene]] are responsible. In turn, immune function decreases and infection opportunities increase. One of the most common mutations deletes 28 DNA [[Biology:Nucleotide|nucleotide]]s from the ''C2'' gene. Therefore, no C2 [[Biology:Protein|protein]] which can help make [[Biology:C3-convertase|C3-convertase]] is produced. Ultimately, this delays/decreases immune response.<ref>{{cite web|last1=Reference|first1=Genetics Home|title=C2 gene|url=https://ghr.nlm.nih.gov/gene/C2#conditions|website=Genetics Home Reference|access-date=21 September 2016}}</ref>
* '''C3''': In terms of deficiency of C3, it has been found that 17 mutations in the ''C3'' gene cause problems with C3. This rare condition mutates or prevents C3 protein from forming, lowering the immune system's ability to protect.<ref>{{cite web|last1=Reference|first1=Genetics Home|title=C3 gene|url=https://ghr.nlm.nih.gov/gene/C3#conditions|website=Genetics Home Reference|access-date=21 September 2016}}</ref>
* '''C4''': [[Medicine:Complement component 4|C4]] deficiency is highly associated with [[Medicine:Systemic lupus erythematosus|systemic lupus erythematosus]].<ref name=scape/> [[Biology:Amyloid beta|Aβ42]], a protein involved in [[Medicine:Alzheimer's disease|Alzheimer's disease]], can cause activation of C4 (even in plasma deficient of C1q).<ref>{{cite journal|last1=Kolev|first1=Martin V|last2=Ruseva|first2=Marieta M|last3=Harris|first3=Claire L|last4=Morgan|first4=B. Paul|last5=Donev|first5=Rossen M|title=Implication of Complement System and its Regulators in Alzheimer's Disease|journal=Current Neuropharmacology|date=1 March 2009|volume=7|issue=1|pages=1–8|doi=10.2174/157015909787602805|pmc=2724661|issn=1570-159X|pmid=19721814}}</ref> At least one study indicates that the genetic variation of C4 plays a role in [[Medicine:Schizophrenia|schizophrenia]].<ref>{{Cite journal|last1=Sekar|first1=Aswin|last2=Bialas|first2=Allison R.|last3=de Rivera|first3=Heather|last4=Davis|first4=Avery|last5=Hammond|first5=Timothy R.|last6=Kamitaki|first6=Nolan|last7=Tooley|first7=Katherine|last8=Presumey|first8=Jessy|last9=Baum|first9=Matthew|date=2016-02-11|title=Schizophrenia risk from complex variation of complement component 4|journal=Nature|volume=530|issue=7589|pages=177–183|doi=10.1038/nature16549|issn=0028-0836|pmc=4752392|pmid=26814963|bibcode=2016Natur.530..177.}}</ref>
{{clear}}

==Diagnosis==
The diagnostic tests used to diagnose a complement deficiency include:<ref name="scape">{{cite web|title=Complement Deficiencies Clinical Presentation: History, Physical, Causes|url=http://emedicine.medscape.com/article/135478-clinical#showall|website=emedicine.medscape.com|access-date=21 September 2016}}</ref>
* CH50 measurement
* Immunochemical methods/test
* C3 deficiency screening
* [[Chemistry:Mannose|Mannose]]-binding lectin (lab study)
* [[Biology:Blood plasma|Plasma]] levels/regulatory proteins (lab study)

===Types===
* Disorders of the proteins that act to '''''inhibit''''' the complement system (such as C1-inhibitor) can lead to an ''overactive'' response, causing conditions such as [[Medicine:Hereditary angioedema|hereditary angioedema]].<ref>{{cite journal|last1=Davis|first1=Alvin E.|title=Biological activities of C1 inhibitor|last2=Mejia|first2=Pedro|last3=Lu|first3=Fengxin|journal=Molecular Immunology|date=1 October 2008|volume=45|issue=16|pages=4057–4063|doi=10.1016/j.molimm.2008.06.028|pmc=2626406|issn=0161-5890|pmid=18674818}}</ref>
* Disorders of the proteins that act to '''''activate''''' the complement system (such as C3) can lead to an ''underactive'' response, causing greater susceptibility to infections.<ref>{{cite journal|last1=Ram|first1=S.|last2=Lewis|first2=L. A.|last3=Rice|first3=P. A.|title=Infections of People with Complement Deficiencies and Patients Who Have Undergone Splenectomy|journal=Clinical Microbiology Reviews|date=7 October 2010|volume=23|issue=4|pages=740–780|doi=10.1128/CMR.00048-09|pmc=2952982|issn=0893-8512|pmid=20930072}}</ref>

==Treatment==
In terms of management for complement deficiency, immunosuppressive therapy should be used depending on the disease presented. A C1-INH concentrate can be used for angio-oedema (C1-INH deficiency).<ref name=pat/><ref name=scape/>

Pneumococcus and ''[[Biology:Haemophilus|Haemophilus]]'' infections can be prevented via immunization.<ref name=pat/> Epsilon-aminocaproic acid could be used to treat hereditary C1-INH deficiency, though the possible side effect of intravascular [[Medicine:Thrombosis|thrombosis]] should be weighed.<ref name=emed/>

==Epidemiology==
C2 deficiency has a prevalence of 1 in about 20,000 people in Western countries.<ref name="pat">{{Cite web|url=https://patient.info/doctor/complement-deficiencies|title=Complement Deficiencies. What are complement deficiencies?|website=patient.info|language=en-GB|access-date=2017-12-31}}</ref>

==See also==
* [[Medicine:Paroxysmal nocturnal hemoglobinuria|Paroxysmal nocturnal hemoglobinuria]]

== References ==
{{Reflist}}

==Further reading==
* {{cite journal|last1=Botto|first1=Marina|title=Links between complement deficiency and apoptosis|journal=Arthritis Research & Therapy|date=1 January 2001|volume=3|issue=4|pages=207–210|doi=10.1186/ar301|pmid=11438036|issn=1478-6362|pmc=128896 |doi-access=free }}
* {{cite book|last1=Aghamohammadi|first1=Asghar|last2=Rezaei|first2=Nima|title=Clinical cases in primary immunodeficiency diseases a problem-solving approach|date=2012|publisher=Springer|location=Berlin|isbn=9783642317859|url=https://books.google.com/books?id=IftYOIDjQbcC&q=terminal+complement+components+Neisseria.&pg=PA334|access-date=21 September 2016|language=en}}

== External links ==
{{Medical resources
|   DiseasesDB     = 1847
|   ICD10          ={{ICD10|D|84|1|d|80}}
|   ICD9           = {{ICD9|279.8}}
|   ICDO           =
|   OMIM           = 217000
|   OMIM_mult      = {{OMIM|120820||none}}, {{OMIM|120900||none}}, {{OMIM|610102||none}}
|   MedlinePlus    =
|   eMedicineSubj  = med
|   eMedicineTopic = 419
|   eMedicine_mult = {{eMedicine2|ped|447}}
|   MeshID         =
}}
{{Medicine}}

[[Category:Syndromes]]

{{Sourceattribution|Complement deficiency}}