Different HLA Class IA Region Complotypes for HLA-A29.2 and -A29.1 Antigens, Identical in Birdshot Retinochoroidopathy Patients or Healthy Individuals

• Published in: Investigative ophthalmology & visual science Vol. 46; no. 9; pp. 3227 - 3232
• Main Authors: Donvito, Beatrice, Monnet, Dominique, Tabary, Thierry, Delair, Emmanuelle, Vittier, Melanie, Reveil, Brigitte, Sivaradjam, Radjagourou, Edelson, Catherine, Philbert, Frederique, Brezin, Antoine P, Cohen, Jacques H. M
• Format: Journal Article
• Language: English
• Published: Rockville, MD ARVO 01-09-2005; Association for Research in Vision and Ophtalmology
• Subjects: Adult; Biological and medical sciences; Choroid Diseases - genetics; DNA Fingerprinting; DNA, Complementary - analysis; Eye and associated structures. Visual pathways and centers. Vision; Female; Fundamental and applied biological sciences. Psychology; Gene Frequency; Hemochromatosis Protein; Histocompatibility Antigens Class I - genetics; Histocompatibility Testing; HLA-A Antigens - genetics; Humans; Male; Membrane Proteins - genetics; Microsatellite Repeats; Middle Aged; Polymerase Chain Reaction; Polymorphism, Genetic; Retinal Diseases - genetics; Uveitis, Posterior - genetics; Vertebrates: nervous system and sense organs; Human; HLA-System; Ophthalmology; Healthy subject; Major histocompatibility system; Class I histocompatibility antigen
• ISSN: 0146-0404; 1552-5783; 1552-5783
• DOI: 10.1167/iovs.04-0858

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.
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).
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.
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.