Different HLA class IA region complotypes for HLA-A29.2 and -A29.1 antigens, identical in birdshot retinochoroidopathy patients or healthy individuals

PURPOSE. Birdshot retinochoroidopathy ( BSCR) is a rare posterior uveitis characterized by distinctive, multiple, hypopigmented choroidal and retinal lesions. At least 96% of patients, if not all, share the major histocompatibility antigen HLA- A29. Although it was hypothesized earlier that more frequently the A* 2902 subtype was closely associated with BSCR, new patients were found to share the A* 2901 subtype and were further investigated. The present study was designated to check patients' HLA- A* 2901 subtyping and the polymorphisms available in the HLA region in patients and control subjects sharing the A* 2901 and A* 2902 subtypes. METHODS. HLA- A29 was assessed and subtyped by molecular biology. cDNA from one patient ( HLA- A* 2901) was sequenced. A29.1 antigenic expression on peripheral blood lymphocytes was checked by microlymphocytotoxicity ( MLCT). Four homozygous A29.2 and 4 heterozygous A29.2 patients, 3 homozygous A29.2 healthy subjects, 3 heterozygous A29.1 patients, and 11 heterozygous A29.1 healthy subjects were tested for the microsatellite alleles MOGa, - b, - c, and e ( of the myelin oligodendrocyte glycoprotein [ MOG] gene), D6S265, D6S510, RF, C5_ 4_ 5, D6S105, and D6S276 and the mutation H63D of the familial hemochromatosis gene ( HFE). RESULTS. The patients' cDNA sequences and MLCT reactivities of HLA- A29.1 subtypes were found to be identical with published data from healthy individuals. Surprisingly, though A* 2901 and A* 2902 differed only by a single mutation ( G376C/ D102H) two strong A* 2901 and A* 2902 complotypes were observed in patients and control subjects, the polymorphisms being identical at all loci near HLA- A, whereas more distant loci exhibited some diversity. CONCLUSIONS. Susceptibility to BSCR thus appeared to be located between the left and right remote markers C5_ 4_ 5 and D6S276, if not relying on the HLA- A29 molecule itself.