Medicine:Deficiency of the interleukin-1–receptor antagonist

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Deficiency of the interleukin-1–receptor antagonist
Other namesInterleukin 1 receptor antagonist deficiency
PDB 1ilr EBI.jpg
Interleukin-1–receptor antagonist
SpecialtyImmunology
SymptomsJoint pain[1]
CausesMutations in IL1RN gene[2][3]
Diagnostic methodGenetic test, Radiological findings[4][3]
TreatmentColchicine [5]

Deficiency of the interleukin-1–receptor antagonist (DIRA) is an autosomal recessive, genetic autoinflammatory syndrome resulting from mutations in IL1RN, the gene encoding the interleukin 1 receptor antagonist.[6][7][2] The mutations result in an abnormal protein that is not secreted, exposing the cells to unopposed interleukin 1 activity. This results in sterile multifocal osteomyelitis, periostitis (inflammation of the membrane surrounding the bones), and pustulosis due to skin inflammation from birth.

Symptoms and signs

Cervical vertebrae

DIRA displays a constellation of serious symptoms which include respiratory distress, as well as the following:[1][7]


Cause

Those affected with DIRA have inherited (via autosomal recessive manner) mutations in IL1RN,[2][3] a gene that encodes a protein known as interleukin 1 receptor antagonist,[8][2] The cytogenetic location of IL1RN is 2q14.1, while its 2:113,099,364-113,134,015 are the genomic coordinates.[3]

Mechanism

Interleukin-1Alpha

The mechanism of deficiency of the interleukin-1–receptor antagonist affects the normal function of IL1RN gene. The protein produced by IL1RN gene prevents the normal activities of interleukin 1(alpha) and interleukin 1(beta). Therefore, the pathophysiologic immune and inflammatory responses are nullified.[3][8] Interleukin 1 receptor antagonist (IL1RN) has a total of five alleles, of those the (IL1RN*1) and (IL1RN*2) are the most common as the other alleles are seen less than 5 percent.[3]

IL-1RN binds to the same cell receptors as the inflammatory protein IL-1, and blocks its inflammatory actions. Without IL-1Ra, the body cannot control systemic inflammation that can be caused by IL-1.[9]

Diagnosis

Those affected with deficiency of the interleukin-1–receptor antagonist can have diagnosis achieved via noting an increase of erythrocyte sedimentation rate, as well as the following:[4][3]

  • Genetic test
  • Radiological findings
  • Clinical findings

Treatment

Colchicine

In terms of treatment a 2013 review indicates that colchicine can be used for DIRA.[5] Additionally there are several other management options such as anakinra, which blocks naturally occurring IL-1.[10][11]

See also

  • Neonatal onset multisystem inflammatory disease (NOMID)

References

  1. ↑ 1.0 1.1 "Deficiency of interleukin-1 receptor antagonist| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program" (in en). https://rarediseases.info.nih.gov/diseases/10516/index. [yes|permanent dead link|dead link}}]
  2. ↑ 2.0 2.1 2.2 2.3 "Osteomyelitis, sterile multifocal, with periostitis and pustulosis - Conditions - GTR - NCBI" (in en). https://www.ncbi.nlm.nih.gov/gtr/conditions/C2748507/. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 "OMIM Entry - * 147679 - INTERLEUKIN 1 RECEPTOR ANTAGONIST; IL1RN" (in en-us). https://omim.org/entry/147679. 
  4. ↑ 4.0 4.1 Griffiths, Christopher; Barker, Jonathan; Bleiker, Tanya; Chalmers, Robert; Creamer, Daniel (2016-02-29) (in en). Rook's Textbook of Dermatology. John Wiley & Sons. pp. 45–7. ISBN 9781118441176. https://books.google.com/books?id=EyypCwAAQBAJ&q=Osteomyelitis,+sterile+multifocal,+with+periostitis+and+pustulosis+diagnosis&pg=SA45-PA7. 
  5. ↑ 5.0 5.1 Ter Haar, Nienke; Lachmann, Helen; Özen, Seza; Woo, Pat; Uziel, Yosef; Modesto, Consuelo; Koné-Paut, Isabelle; Cantarini, Luca et al. (May 2013). "Treatment of autoinflammatory diseases: results from the Eurofever Registry and a literature review". Annals of the Rheumatic Diseases 72 (5): 678–685. doi:10.1136/annrheumdis-2011-201268. ISSN 1468-2060. PMID 22753383. https://iris.unito.it/bitstream/2318/120618/1/OK_897279_Treatment%20of%20autoinflammatory%20diseases_4aperto.pdf. 
  6. ↑ Liaison, Janet Austin, Office of Communications and Public (2017-04-21). "Autoinflammatory Diseases" (in en). https://www.niams.nih.gov/Health_Info/Autoinflammatory/default.asp. 
  7. ↑ 7.0 7.1 "OMIM Entry - # 612852 - OSTEOMYELITIS, STERILE MULTIFOCAL, WITH PERIOSTITIS AND PUSTULOSIS; OMPP" (in en-us). https://omim.org/entry/612852. 
  8. ↑ 8.0 8.1 Reference, Genetics Home. "IL1RN gene" (in en). https://ghr.nlm.nih.gov/gene/IL1RN#conditions. 
  9. ↑ Rezaei, Nima; Aghamohammadi, Asghar; Notarangelo, Luigi D. (2016-11-30) (in en). Primary Immunodeficiency Diseases: Definition, Diagnosis, and Management. Springer. p. 410. ISBN 9783662529096. https://books.google.com/books?id=VsiiDQAAQBAJ&q=Osteomyelitis,+sterile+multifocal,+with+periostitis+and+pustulosis+treatment&pg=PA410. 
  10. ↑ (in en) Nelson Textbook of Pediatrics: The field of pediatrics. Elsevier Health Sciences. 2016. p. 1203. ISBN 9781455775668. https://books.google.com/books?id=mseNCgAAQBAJ&q=Osteomyelitis,+sterile+multifocal,+with+periostitis+and+pustulosis+treatment&pg=PA1203. Retrieved 22 June 2017. 
  11. ↑ Pazyar, N; Feily, A; Yaghoobi, R (November 2012). "An overview of interleukin-1 receptor antagonist, anakinra, in the treatment of cutaneous diseases.". Current Clinical Pharmacology 7 (4): 271–5. doi:10.2174/157488412803305821. ISSN 2212-3938. PMID 22794157. subscription required

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