Deficiency of the interleukin-1–receptor antagonist

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Deficiency of the interleukin-1–receptor antagonist
Other names: Interleukin 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.[medical citation needed]

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

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]

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.[11][12]

See also

References

  1. 1.0 1.1 "Deficiency of interleukin-1 receptor antagonist| Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2017-06-11.{{cite web}}: CS1 maint: url-status (link)
  2. 2.0 2.1 2.2 2.3 "Osteomyelitis, sterile multifocal, with periostitis and pustulosis - Conditions - GTR - NCBI". www.ncbi.nlm.nih.gov. Archived from the original on 2018-10-30. Retrieved 2017-06-11.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 "OMIM Entry - * 147679 - INTERLEUKIN 1 RECEPTOR ANTAGONIST; IL1RN". omim.org. Archived from the original on 2017-05-10. Retrieved 2017-06-21.
  4. 4.0 4.1 Griffiths, Christopher; Barker, Jonathan; Bleiker, Tanya; Chalmers, Robert; Creamer, Daniel (2016-02-29). Rook's Textbook of Dermatology. John Wiley & Sons. pp. 45–7. ISBN 9781118441176. Archived from the original on 2023-11-03. Retrieved 2023-02-22.
  5. 5.0 5.1 Ter Haar, Nienke; Lachmann, Helen; Özen, Seza; Woo, Pat; Uziel, Yosef; Modesto, Consuelo; Koné-Paut, Isabelle; Cantarini, Luca; Insalaco, Antonella (May 2013). "Treatment of autoinflammatory diseases: results from the Eurofever Registry and a literature review" (PDF). Annals of the Rheumatic Diseases. 72 (5): 678–685. doi:10.1136/annrheumdis-2011-201268. hdl:2318/120618. ISSN 1468-2060. PMID 22753383. S2CID 9558024. Archived (PDF) from the original on 2022-10-24. Retrieved 2023-02-22.
  6. Liaison, Janet Austin, Office of Communications and Public (2017-04-21). "Autoinflammatory Diseases". www.niams.nih.gov. Archived from the original on 2017-06-27. Retrieved 2017-06-11.
  7. 7.0 7.1 "OMIM Entry - # 612852 - OSTEOMYELITIS, STERILE MULTIFOCAL, WITH PERIOSTITIS AND PUSTULOSIS; OMPP". omim.org. Archived from the original on 2017-05-10. Retrieved 2017-06-11.
  8. 8.0 8.1 Reference, Genetics Home. "IL1RN gene". Genetics Home Reference. Archived from the original on 2017-01-31. Retrieved 2017-06-12.
  9. Rezaei, Nima; Aghamohammadi, Asghar; Notarangelo, Luigi D. (2016-11-30). Primary Immunodeficiency Diseases: Definition, Diagnosis, and Management. Springer. p. 410. ISBN 9783662529096. Archived from the original on 2023-11-03. Retrieved 2023-02-22.
  10. Goldbach-Mansky, R. (March 2012). "Immunology in clinic review series; focus on autoinflammatory diseases: update on monogenic autoinflammatory diseases: the role of interleukin (IL)-1 and an emerging role for cytokines beyond IL-1". Clinical and Experimental Immunology. 167 (3): 391–404. doi:10.1111/j.1365-2249.2011.04533.x. ISSN 1365-2249. Archived from the original on 1 November 2023. Retrieved 1 November 2023.
  11. Nelson Textbook of Pediatrics: The field of pediatrics. Elsevier Health Sciences. 2016. p. 1203. ISBN 9781455775668. Archived from the original on 3 November 2023. Retrieved 22 June 2017.
  12. 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

Further reading

External links

Classification
External resources