Association of human leukocyte antigen class II alleles with response to immunosuppressive therapy in Korean aplastic anemia patients

Abstract

HLA-DR15 (DR2) is overrepresented in aplastic anemia (AA) patients, and its presence is associated with a better response to cyclosporine-based immunosuppressive therapy (IST). However, little is known about other human leukocyte antigen (HLA) alleles affecting therapy response. We investigated 37 Korean patients with severe AA for the association of HLA class II alleles with response to IST: cyclosporine A combined with antithymocyte globulin or antilymphocyte globulin. Molecular or serologic typing of HLA-DR and HLA-DQ alleles was performed. In responders (13/37, 35.1%), the frequency of HLA-DR15 was increased (69.2% vs 8.3%, p = 0.0002) and that of DR4 was decreased (7.7% vs 66.7%, p = 0.0007) compared with nonresponders. The response rate was significantly higher in DR15(+) than in DR15(-) (81.8% vs 15.4%, p = 0.0002) and in DR4(-) than in DR4(+) patients (60.0% vs 5.9%, p = 0.0007). The response rates in the best (DR15(+)/DR4(-)), intermediate, and poor response groups (DR15(-)/DR4(+)) were 88.9, 38.5, and 0%, respectively (p = 0.00001). At the allelic level, DRB1*1501 and closely linked DQB1*0602 were associated with a good response and DRB1*0405 and closely linked DQB1*0401 with a poor response to IST. HLA-DR typing may be useful for predicting a response to IST in AA patients. (C) 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.