HLA-DR15 (DR2) is overrepresented in myelodysplastic syndrome and aplastic anemia and predicts a response to immunosuppression in myelodysplastic syndrome.

The extent and importance of autoimmune mechanisms in myelodysplastic syndrome (MDS) and the role of immunosuppression in the treatment of this disease are not well defined. We report overrepresentation of HLA-DR2 and its serologic split HLA-DR15 in both MDS and aplastic anemia (AA). Four clinically and ethnically defined patient groups were analyzed. The HLA-DR15 antigen frequencies among North American white MDS patients (n = 72) and AA patients (n = 59), who received immunosuppressive treatment at the National Institutes of Health (NIH), were 36% and 42%, respectively. These antigen frequencies were significantly higher than that of the control population of 240 North American white NIH blood donors typed for HLA antigens by the same molecular technique (HLA-DR15, 21.3%, P =.01 for MDS, P <.001 for AA). Among North American white patients reported in the International Bone Marrow Transplant Registry (IBMTR), 30% of 341 MDS patients and 33% of 364 AA patients were positive for HLA-DR2. These antigen frequencies were higher than those reported for the general North American white population (HLA-DR2, 25.3%, P =.089 for MDS, P =.01 for AA). The DR15 and DR2 frequencies were significantly increased in MDS refractory anemia (RA) (P =.036 and P =.01, respectively) but not MDS refractory anemia with excess blasts. In the NIH MDS patients, HLA-DR15 was significantly associated with a clinically relevant response to antithymocyte globulin (ATG) or cyclosporine immunosuppression (multivariate analysis, P =.008). In MDS with RA, DR15 may be useful as a guide to pathophysiology, prognosis, and treatment.