HLA loss in aplastic anemia

Abstract

In immune aplastic anemia, somatic loss of specific HLA class I alleles enables hematopoietic stem cells to evade T-cell-mediated destruction. In Japanese patients, HLA-B^*40:02, HLA-A^*02:06, HLA-A^*02:01, HLA-A^*31:01, and HLA-B^*54:01 are frequently lost and are also overrepresented, suggesting their involvement in the pathogenic antigen presentation. Detection of HLA-deficient blood cells is useful for distinguishing immune aplastic anemia from non-immune bone marrow failure syndromes. Furthermore, the specific lost HLA class I alleles correlate with clinical outcomes following immunosuppressive therapy and allogeneic hematopoietic stem cell transplantation. Hematologic recovery after successful antithymocyte globulin-based immunosuppressive therapy is driven by the reexpansion of HLA-intact hematopoietic stem cells. However, recent evidence indicates that spontaneous remission occurs through the selective proliferation of HLA-deficient clones in the absence of antithymocyte globulin. This review outlines the historical context, detection strategies, and clinical significance of HLA loss in aplastic anemia.