Immunogenetic factors determining the evolution of T‐cell large granular lymphocyte leukaemia and associated cytopenias

Summary T‐cell large granular lymphocyte leukaemia (T‐LGL) is a chronic clonal proliferation of cytotoxic T lymphocytes (CTL). T‐LGL presents with cytopenias, often accompanied by autoimmune diseases, suggesting clonal transformation arising from an initially polyclonal immune response. Various immunogenetic predisposition factors, previously described for both immune‐mediated bone marrow failure and autoimmune conditions, may promote T‐LGL evolution and/or development of cytopenias. The association of T‐LGL was analysed with a number of immunogenetic factors in 66 patients, including human leucocyte antigen (HLA) and killer‐cell immunoglobulin‐like receptor (KIR) genotype, KIR/KIR‐L mismatch, CTLA‐4 (+49 A/G),CD16−158V/F, CD45 polymorphisms, cytokine single nucleotide polymorphisms including: TNF‐α (−308G/A), TGF‐β1 (codons 10 C/T, 25 G/C), IL‐10 (−1082 G/A), IL‐6 (−174 C/G), and IFN‐γ(+874 T/A). A statistically significant increase in A/A genotype for TNF‐α−308, IL‐10–1082, andCTLA‐4 +49 was observed in T‐LGL patients compared with control, suggesting that the G allele serves a protective role in each case. No association was found between specific KIR/HLA profile and disease. KIR/KIR‐L analysis revealed significant mismatches between KIR3DL2 and KIR2DS1 and their ligands HLA‐A3/11 and HLA‐C group 2 (P = 0·03 and 0·01 respectively); the biological relevance of this finding is questionable. The significance of additional genetic polymorphisms and their clinical correlation to evolution of T‐LGL requires future analysis.