Immunological features of acquired pure red cell aplasia: Specific human leucocyte antigen alleles, signal transducer and activator of transcription 3 mutations and a unique T-cell receptor beta motif.

T-cell abnormalities have been implicated in the pathogenesis of acquired pure red cell aplasia (PRCA), particularly in its major subtypes such as idiopathic PRCA, thymoma-associated PRCA and large granular lymphocytic leukaemia (LGLL)-associated PRCA, and the precise details remain unclear. Furthermore, signal transducer and activator of transcription 3 (STAT3) mutations are frequently detected in PRCA patients, but their association with cellular immune abnormalities is not well understood. In order to elucidate the immunogenetic backgrounds of PRCA, we conducted human leucocyte antigen (HLA) typing in 39 PRCA patients. The results showed a significantly higher allele frequency of HLA-B*44:03:01, -C*14:03, -DRB1*13:02, compared to HLA database. Additionally, analysis of inferred HLA haplotypes revealed significantly increased frequencies of two haplotypes: HLA-A*24:02-C*07:02-B*07:02-DRB1*01:01 and -A*33:03-C*14:03-B*44:03:01-DRB1*13:02. Clonotypic analyses of T-cell receptor beta (TCRβ) chain revealed that 80% of the PRCA cases possessed mono- or oligoclonally expanded T cells. Particularly among those with STAT3 mutations, the 'QGXG' motif in 15 AA sequences of TCRβ complementarity-determining regions 3 (CDR3) regions was specifically recognized. These findings suggest that a specific immunogenetic background defined by particular HLA alleles, the expansion of somewhat limited T-cell clones and STAT3-mutated T cells are involved in the pathogenesis of chronic acquired PRCA.