T-cell receptor excision circles and repertoire diversity in children with profound T-cell immunodeficiency

Background/Purpose(s): Approximately 40% of patients with profound T-cell immunodeficiency have no identified molecular basis. Early assessment of T-cell impairment is vital for medical intervention, if hematopoietic stem cell transplantation is needed. The dynamics of T-cell receptor excision circles (TRECs) revealing recent thymic output of naïve T cell and T-cell receptor (TCR) repertoire diversity reflecting broader responses to multiple antigens, are both important in resisting infections. Methods: The TRECs value and TCR repertoire diversity were evaluated from peripheral blood mononuclear cells in patients with primary severe T cell immunodeficiency, to elucidate the T-cell response. Results: In seven children with <30% of normal phytohemagglutinin (PHA)-stimulated lymphocyte proliferation, including two IL2RG (Try74Gly and Arg226Lys, X-linked) and one RAG2 mutations [(Ser205Tyr) and (del 1366T, frameshift, 484stop); autosomal recessive], lower TRECs value and oligo- and restricted TCR diversity patterns, were associated with increased susceptibility to opportunistic infections, but not inversely correlated to the severity and frequency of infections. Three patients had successful cord blood stem cell transplantation which reconstructed the T cell immunodeficiency, with normalized TRECs value and TCR repertoire diversity at 6 months post-transplant, without clinical events. Conclusion: Low TRECs value and restricted TCR repertoire diversity can help in the early diagnosis of T cell immunodeficiency before irreversible sequelae and in the monitoring of post-transplantation T-cell immune reconstruction.