The Impact of HLA-A29 Homozygosity and of the Second HLA-A Allele on Susceptibility and Severity of Birdshot Chorioretinitis

• Published in: Investigative ophthalmology & visual science 2024-11, Vol.65 (13), p.47
• Main Authors: Loeliger, Jordan, Lhotte, Romain, Gelfman, Sahar, Stahl, Eli A, Monnet, Dominique, Clichet, Valentin, Imikirene, Linda, Kecili, Souhila, Taupin, Jean-Luc, Tabary, Thierry, Cohen, Jacques H M, Brézin, Antoine P
• Format: Article
• Language: English
• Subjects: Adult; Alleles; Birdshot Chorioretinopathy - genetics; Chorioretinitis - diagnosis; Chorioretinitis - genetics; Clinical and Epidemiologic Research; Female; Gene Frequency; Genetic Predisposition to Disease; HLA-A Antigens - genetics; Homozygote; Humans; Male; Middle Aged; Severity of Illness Index
• ISSN: 1552-5783; 0146-0404; 1552-5783
• DOI: 10.1167/iovs.65.13.47

HLA-A29 is the main susceptibility factor for birdshot chorioretinitis (BSCR). Our study assessed the impact of the second HLA-A allele alongside HLA-A29 on BSCR severity and susceptibility, focusing on HLA-A29 homozygous patients and those with alleles from the HLA-Aw19 group. We included 120 additional cases to our previous analysis of 286 patients with BSCR, all HLA-A29 positive. Patients were categorized based on the second allele being also HLA-A29 (A29/nonA29 vs. A29/A29) or belonging to the HLA-Aw19 family, including A29, A30, A31, and A33 (A29/nonAw19 vs. A29/Aw19). HLA-A32 was analyzed separately (A29/nonA32 vs. A29/A32). The prevalence of these groups among patients with BSCR was compared with their frequencies in a sample of 151,997 French subjects. Disease severity was approximated by assessing disease onset and visual function at the last visit and was compared between patient groups. When comparing the HLA-A29-positive patients with BSCR to HLA-A29-positive French subjects, we found an overrepresentation of HLA-A29 for the second HLA-A allele (χ² = 4.34; P = 0.037; odds ratio, 1.57; confidence interval, 1.01-2.44). Within the HLA-Aw19 broad antigen family, HLA-A32 was found to be under-represented (χ² = 6.15; P = 0.013; odds ratio, 0.40; confidence interval, 0.19-0.85). The nature of the second HLA-A allele did not impact disease severity. Homozygosity for HLA-A29 increased the risk of developing BSCR without affecting disease severity. The under-representation of HLA-A32 in patients with BSCR suggests a potential protective role.