Immunological abnormalities of chronic large granular lymphocytosis

Chronic large granular lymphocytosis is a relatively common condition and comprises a clinically heterogenous group of patients. Phenotypically these can be divided into CD3+ (T cell) and CD3-(NK cell) expansions. They are characterized by a benign clinical course and a mild lymphocytosis, though a specific subgroup have a history of auto-immune disease and cytopenias. In order to develop a better understanding of the immunological abnormalities associated with this condition we examined systematically serum samples from 92 such patients for the presence of auto-antibodies, acute phase proteins and immunoglobulin levels. Auto-antibodies were found in 34% of patients and rheumatoid factor in 26%, though only half of these had active arthritis. Anti-neutrophil antibodies were negative in all cases. Quantitative immunoglobulin abnormalities were frequent with a distinct paraprotein present in three patients. The high incidence of multiple immunological abnormalities in these patients ranged from polyclonal hypergammaglobulinaemia and auto-antibodies through to monoclonal gammopathy. The aetiology of these abnormalities was unclear and undoubtedly complex, and should necessarily form part of the diagnostic investigations for all patients with persistent large granular lymphocyte expansions.