Frequent mutations in CD8 T cells from patients with pure red cell aplasia.

Dysregulation of T-cell-mediated immunity is responsible for acquired pure red cell aplasia (PRCA). Although mutations are frequently detected in patients with T-cell large granular lymphocytic leukemia (T-LGLL), which is often complicated by PRCA and which is also reported to be associated with acquired aplastic anemia (AA) and myelodysplastic syndrome (MDS), whether -mutated T cells are involved in the pathophysiology of PRCA and other types of bone marrow failure remains unknown. We performed mutation analyses of the peripheral blood mononuclear cells from PRCA patients (n = 42), AA (n = 54), AA-paroxysmal nocturnal hemoglobinuria (AA-PNH; n = 7), and MDS (n = 21) using an allele-specific polymerase chain reaction and amplicon sequencing. mutations were not detected in any of the 82 patients with AA/PNH/MDS but were detected in 43% of the 42 PRCA patients. In all 7 -mutation-positive patients who were studied, the mutations were restricted to sorted CD8 T cells. The prevalence of mutation in idiopathic, thymoma-associated, autoimmune disorder-associated, and T-LGLL-associated PRCA was 33% (5 of 15), 29% (2 of 7), 20% (1 of 5), and 77% (10 of 13), respectively. The -mutation-positive patients were younger (median age, 63 vs 73 years; = .026) and less responsive to cyclosporine (46% [6 of 13] vs 100% [8 of 8]; = .0092) in comparison with -mutation-negative patients. The data suggest that -mutated CD8 T cells may be closely involved in the selective inhibition of erythroid progenitors in PRCA patients.