A new HLA extended haplotype containing the A*2910 allele in birdshot retinochoroidopathy: susceptibility narrowed to the HLA molecule itself.
OBJECTIVE
Birdshot retinochoroidopathy (BSRC) is a rare posterior uveitis characterized by distinctive, multiple, hypopigmented choroidal and retinal lesions. Most, if not all, patients are white and share the major histocompatibility antigen HLA-A29. Furthermore, the A*2902 subtype is closely associated with BSRC, and only a very few patients share the A*2901 subtype. Surprisingly, although A*2901 and A*2902 differ only by a single mutation (D102H), studies of microsatellites located near HLA-A have shown that two strong A*2901 and A*2902 extended haplotypes are observed in patients and control subjects. The present study analyzes the HLA-A extended haplotype of two patients who were HLA-A*2910 carriers.


METHODS
Among 180 patients who fulfilled internationally defined criteria for the diagnosis of BSRC and who were HLA-A29 subtyped, two patients were found to be HLA-A*2910 carriers. These patients were tested for the microsatellite alleles MOGa, -b, -c, and -e (of the myelin oligodendrocyte glycoprotein [MOG] gene) and D6S265, D6S510, RF, C5_4_5, and D6S105.


RESULTS
Although A*2902 and A*2910 differed by only a single mutation, (E177K) a new A*2910 extended haplotype was found to be distinct from the A*2901 and A*2902 extended haplotypes previously described in patients and control subjects. Among all studied microsatellite markers, no allele was shared by these extended haplotypes.


CONCLUSIONS
These results suggest that susceptibility to BSRC is linked to the histocompatibility HLA-A29 molecule itself, although the development of the disease also involves inherited or probably acquired factors not linked to the major histocompatibility complex.
Donvito
Béatrice
B
Laboratoire d'Immunologie, Centre Hospitalo-Universitaire Reims, Université de Reims Champagne-Ardenne, Reims, France.
Monnet
Dominique
D
Tabary
Thierry
T
Delair
Emmanuelle
E
Vittier
Mélanie
M
Réveil
Brigitte
B
Chiquet
Christophe
C
Brézin
Antoine P
AP
Cohen
Jacques H M
JH
D000368:Aged; D000483:Alleles; D002825:Chorioretinitis / Q000235:genetics*; D005260:Female; D005451:Fluorescein Angiography; D020022:Genetic Predisposition to Disease; D005938:Glucocorticoids / Q000627:therapeutic use; D015234:HLA-A Antigens / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006650:Histocompatibility Testing; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D018895:Microsatellite Repeats; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015866:Uveitis, Posterior / Q000235:genetics*
D005938:Glucocorticoids; D015234:HLA-A Antigens; C509093:HLA-A*29:10 antigen; D016756:Immunoglobulins, Intravenous