Different HLA class IA region complotypes for HLA-A29.2 and -A29.1 antigens, identical in birdshot retinochoroidopathy patients or healthy individuals.
OBJECTIVE
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.
Donvito
Béatrice
B
Laboratoire d'Immunologie EA 3798, Institut Fédératif de Recherche, 53 Université de Reims Champagne Ardenne, CHU Reims 51092, France.
Monnet
Dominique
D
Tabary
Thierry
T
Delair
Emmanuelle
E
Vittier
Mélanie
M
Réveil
Brigitte
B
Sivaradjam
Radjagourou
R
Edelson
Catherine
C
Philbert
Frédérique
F
Brézin
Antoine P
AP
Cohen
Jacques H M
JH
D000328:Adult; D015862:Choroid Diseases / Q000235:genetics*; D016172:DNA Fingerprinting; D018076:DNA, Complementary / Q000032:analysis; D005260:Female; D005787:Gene Frequency; D015234:HLA-A Antigens / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D018895:Microsatellite Repeats; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012164:Retinal Diseases / Q000235:genetics*; D015866:Uveitis, Posterior / Q000235:genetics*
D018076:DNA, Complementary; C103673:HFE protein, human; D015234:HLA-A Antigens; C035524:HLA-A29 antigen; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins