Autoimmune and alloimmune phenomena in patients with aplastic anemia: cytotoxicity against autologous lymphocytes and lymphocytes from HLA identical siblings

We have studied peripheral blood lymphocytes of 117 patients with severe aplastic anemia and 237 healthy individuals for reactivity against autologous lymphocytes and/or lymphocytes from HLA-identical siblings using a 51Cr release assay. Lymphocytes from 29% of the patients exhibited reactivity against their own lymphocytes, while only 3% of lymphocytes from normal individuals showed such reactivity. Lymphocytes from 49% of the patients showed reactivity against lymphocytes from their HLA-identical siblings compared to 4% of normal individuals. Correlation existed between allogeneic and autologous reactivities (p < 0.001), suggesting a common pathway for cytotoxicity. Both reactivities showed an association with extremely low granulocyte counts (p < 0.01) and an inability of the patient's mononulcear cells to stimulate in allogeneic mixed leukocyte culture (p < 0.05) as well as an inverse correlation with time from diagnosis (p < 0.001). At least two explanations exist for the transfusion-independent autologous and allogeneic cytotoxicities: (1) they could be epiphenomena secondary to the stem cell defect, such as the loss of a cell that suppresses (or regulates) naturally occurring cytotoxic cells, or (2) they may be involved in the cause of the disease.