Interleukin 1 receptor antagonist deficiency
The IL1RN gene at 2q13 codes for the 177 amino acid interleukin-1 receptor antagonist protein which has four isoforms. One is secreted and three are cytosol isoforms which are predominantly expressed in epithelial cells. Isoform 2 is also known as: icIL-1ra, isoform 3 as icIL-1ra type II. Isoform 1 inhibits interleukin-1 by binding to interleukin-1 receptor type 1 and preventing its association with the coreceptor interleukin-1 receptor accessory protein for signalling. It has no interleukin-1 like activity. A bioengineered nonglycerated form is marketed as anakinra.
- Interleukin 1 receptor antagonist deficiency (DIRA, deficiency of the interleukin-1–receptor antagonist, OMIM:612852) is a loss of function autoinflammatory disease of skin and bone resulting in sterile multifocal osteomyelitis, periostitis, and pustulosis from birth.
- similar to NOMID with:
- Erythematous macular rash with central pustules
- Balloonlike widening of the anterior rib ends
- High ESR and CRP without fever
- attacks of seemingly unprovoked inflammation without significant levels of autoantibodies and autoreactive T-cells.
- Lytic bone lesions (usually)
- Treatment is with anakinra.
- Microvascular complications of diabetes 4 (MVCD4, OMIM:612628)
- Risk of diabetic nephropathy or osteoporosis and more severe systemic lupus erythematosus, ulcerative colitis and alopecia areata are associated with some polymorphisms of the gene. Other gene associations are with multiple sclerosis progression and risk of gastric cancer after helicobacter pylori infection.
- ↑ Aksentijevich I, Masters SL, Ferguson PJ, Dancey P, Frenkel J, van Royen-Kerkhoff A, Laxer R, Tedgård U, Cowen EW, Pham TH, Booty M, Estes JD, Sandler NG, Plass N, Stone DL, Turner ML, Hill S, Butman JA, Schneider R, Babyn P, El-Shanti HI, Pope E, Barron K, Bing X, Laurence A, Lee CC, Chapelle D, Clarke GI, Ohson K, Nicholson M, Gadina M, Yang B, Korman BD, Gregersen PK, van Hagen PM, Hak AE, Huizing M, Rahman P, Douek DC, Remmers EF, Kastner DL, Goldbach-Mansky R. An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist. The New England journal of medicine. 2009 Jun 4; 360(23):2426-37.(Link to article – subscription may be required.)
- ↑ Reddy S, Jia S, Geoffrey R, Lorier R, Suchi M, Broeckel U, Hessner MJ, Verbsky J. An autoinflammatory disease due to homozygous deletion of the IL1RN locus. The New England journal of medicine. 2009 Jun 4; 360(23):2438-44.(Link to article – subscription may be required.)
- ↑ Lee SH, Ihm CG, Sohn SD, Lee TW, Kim MJ, Koh G, Oh SJ, Woo JT, Kim SW, Kim JW, Kim YS, Lee BC, Kim SD, Cho BS, Lee HJ, Chung JH. Polymorphisms in interleukin-1 beta and Interleukin-1 receptor antagonist genes are associated with kidney failure in Korean patients with type 2 diabetes mellitus. American journal of nephrology. 2004 Jul-Aug; 24(4):410-4.(Link to article – subscription may be required.)
- ↑ Langdahl BL, Løkke E, Carstens M, Stenkjaer LL, Eriksen EF. Osteoporotic fractures are associated with an 86-base pair repeat polymorphism in the interleukin-1--receptor antagonist gene but not with polymorphisms in the interleukin-1beta gene. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2000 Mar; 15(3):402-14.
- ↑ Blakemore AI, Tarlow JK, Cork MJ, Gordon C, Emery P, Duff GW. Interleukin-1 receptor antagonist gene polymorphism as a disease severity factor in systemic lupus erythematosus. Arthritis and rheumatism. 1994 Sep; 37(9):1380-5.
- ↑ Mansfield JC, Holden H, Tarlow JK, Di Giovine FS, McDowell TL, Wilson AG, Holdsworth CD, Duff GW. Novel genetic association between ulcerative colitis and the anti-inflammatory cytokine interleukin-1 receptor antagonist. Gastroenterology. 1994 Mar; 106(3):637-42.
- ↑ Tarlow JK, Clay FE, Cork MJ, Blakemore AI, McDonagh AJ, Messenger AG, Duff GW. Severity of alopecia areata is associated with a polymorphism in the interleukin-1 receptor antagonist gene. The Journal of investigative dermatology. 1994 Sep; 103(3):387-90.
- ↑ Schrijver HM, Crusius JB, Uitdehaag BM, García González MA, Kostense PJ, Polman CH, Peña AS. Association of interleukin-1beta and interleukin-1 receptor antagonist genes with disease severity in MS. Neurology. 1999 Feb; 52(3):595-9.
- ↑ El-Omar EM, Carrington M, Chow WH, McColl KE, Bream JH, Young HA, Herrera J, Lissowska J, Yuan CC, Rothman N, Lanyon G, Martin M, Fraumeni JF, Rabkin CS. Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature. 2000 Mar 23; 404(6776):398-402.(Link to article – subscription may be required.)