HLA and tumour necrosis factor (TNF) polymorphisms in ocular Behçet’s disease

Abstract

The role of HLA-B*51 and other major histocompatibility complex (MHC) genes in Behçet's disease (BD) remains unknown. We have performed HLA and tumour necrosis factor (TNF) polymorphism analysis in BD and evaluated their contribution to ocular disease. In this study, 102 patients and 115 controls of Middle Eastern descent were investigated by HLA and B*51 subtyping using novel primers, and by LT alpha NCo 1 and TNF 308 promoter polymorphism analysis. The frequency of the HLA-B*51 family of alleles was raised in patients compared to controls (66% vs. 15%, Pc=2.5x10(-12), OR=10.9). The odds ratio (OR) of this group of alleles for subgroups of patients was as follows: non-ocular patients 7.8, all ocular patients 12.6, blind patients >22. HLA-B*51 subtyping detected B*5101, 07, 08 and 09 alleles, with a similar frequency among patients and controls. HLA-Cw*1602 was associated with B*5108, but was not an independent risk factor for disease. The LT alpha (TNFB*2) allele was associated with HLA-B*51 among patients and the frequency of this allele was significantly higher among completely blind patients compared to both non-ocular patients (P=0.048, OR >3.6) and to healthy controls (P=0.022, OR >4.3). The rare TNF-2 polymorphism at the TNF -308 promoter position was associated with HLA-B*50 (not B*51), and was not associated with BD. Thus, in this population the HLA*B51 family of alleles is a strong risk factor for BD, and in particular the development of ocular disease. HLA-B*51 subtyping did not define new markers for BD. A primary role for TNF gne polymorphisms in BD was not identified, but co-expression of the TNFB*2 allele with HLA-B*51 may contribute to severity of ocular disease.

Cytokines and Chemokines in Uveitis - Is there a Correlation with Clinical Phenotype?

“…The TNF promoter allele TNF-1031C has been recently reported to be associated with BD susceptibility in Caucasoid patients, 110 and the co-expression of the TNF-β*2 allele with HLA-B*51 has also been found to contribute to the severity of ocular disease. 111 More recently, it has been shown that susceptibility to BD has also been documented to be significantly increased in patients carrying the IL-1β +3953T allele and TT genotype, which correlate with increased IL-1β secretion in vitro. 112 IL-1β levels appear to be not significantly different from controls in the aqueous humor of BD-associated uveitis in a recent study of five samples, but it is not clear whether these patients were on treatment at the time of sampling.…”

Anmerkungen zur Pathogenese des Morbus Behçet

“…Dieser Genotyp liegt bei ca. 40-80% der MB-Patienten vor, während dies in einer gesunden Vergleichspopulation bei nur 8% (Europa) und 24% (Türkei) der Fall ist [28]. Je nach geografischer Verteilung erhöht sich das relative Risiko, einen MB zu entwickeln, bei HLA-B51 + -Individuen auf 1,4 in Portugal, in Deutschland auf ca.…”

Osteonekrosen bei Morbus Adamantiades-Beh�et: Diagnostik, Therapie und Verlauf

“…Genetische Untersuchungen konnten eine Assoziation dieser seltenen Erkrankung mit dem HLA B51-Allel zeigen (20). Andere Arbeitsgruppen betonen die pathogenetische Bedeutung von erhöhten c d-T-Zellzahlen im peripheren Blut sowie die Wirkung der sekretierten Immunmediatoren TNF-a, Inteferon-c, der autoreaktiven Th1-Zytokine und Interleukin-12 (7).…”