Roles of DRB1 *1501 and DRB1 *1502 in the pathogenesis of aplastic anemia.
OBJECTIVE
Although a number of reports have documented a significantly increased incidence of HLA-DR15 in aplastic anemia (AA), the exact role of HLA-DR15 in the immune mechanisms of AA remains unclear. We herein clarify the difference between DRB1( *)1501 and DRB1( *)1502, the two DRB1 alleles that determine the presentation of HLA-DR15, in the pathophysiology of AA.


METHODS
We investigated the relationships of the patients( *) HLA-DRB1 allele with both the presence of a small population of CD55(-)CD59(-) (PNH-type) blood cells and the response to antithymocyte globulin (ATG) plus cyclosporin (CsA) therapy in 140 Japanese AA patients.


RESULTS
Of the 30 different DRB1 alleles, only DRB1( *)1501 (33.6% vs 12.8%, p(c) < 0.01) and DRB1( *)1502 (43.6% vs 24.4%, p(c) < 0.01) displayed significantly higher frequencies among the AA patients than among a control. AA patients possessing HLA-DR15 tended to be old, and especially, the frequency of DRB1( *)1502 in patients 40 years of age and older (52.4%) was markedly higher than that in those younger than 40 years old (16.2%, p(c) < 0.01). Only DRB1( *)1501 was significantly associated with the presence of a small population of PNH-type cells and it also showed a good response to ATG plus CsA therapy in a univariate analysis. A multivariate analysis showed only the presence of a small population of PNH-type cells to be a significant factor associated with a good response to the immunosuppressive therapy (p < 0.01).


CONCLUSIONS
Although both DRB1( *)1501 and DRB1( *)1502 contribute to the development of AA, the methods of contribution differ between the two alleles.
Sugimori
Chiharu
C
Cellular Transplantation Biology, Division of Cancer Medicine, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.
Yamazaki
Hirohito
H
Feng
Xingmin
X
Mochizuki
Kanako
K
Kondo
Yukio
Y
Takami
Akiyoshi
A
Chuhjo
Tatsuya
T
Kimura
Akinori
A
Teramura
Masanao
M
Mizoguchi
Hideaki
H
Omine
Mitsuhiro
M
Nakao
Shinji
S
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000741:Anemia, Aplastic / Q000209:etiology* / Q000276:immunology* / Q000628:therapy; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D001773:Blood Cells; D002648:Child; D016572:Cyclosporine / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology / Q000502:physiology*; D059810:HLA-DR Serological Subtypes; D059811:HLA-DRB1 Chains; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D000961:Antilymphocyte Serum; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C106559:HLA-DR15 antigen; D059811:HLA-DRB1 Chains; C489631:HLA-DRB1*15:01 antigen; D016572:Cyclosporine