Autoimmunity and b-cell dysfunction in chronic proliferative disorders of large granular lymphocytes/natural killer cells

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Abstract
Clinical and laboratory findings of B‐cell immune dysfunction were evaluated in ten patients with a large granular lymphocyte/natural killer cell proliferative disease (LGL/NK‐PD). Increased immunoglobulin synthesis with autoantibody formation was documented: polyclonal hypergammaglobulinaemia (six patients), neutrophil autoantibody (one patient), antinuclear antibody (one patient), and rheumatoid factor (five patients). In addition, serum beta2‐microglobulin level was raised in seven patients, a benign monoclonal gammopathy was detected in one, and concurrent B‐type hairy cell leukemia in another. Most patients experienced the complications of hemocytopenia, polyarthritis or rheumatoid arthritis, and immediate allergic reactions to drugs or environmental substances, rather than from symptoms of progressive LGL/NK‐PD. A review of the literature confirms that an increased immunoglobulin production is common in LGL/NK‐PD, and that patients are likely to develop multiple autoantibodies. The incapacity of proliferating, abnormal LGL/NK cells to suppress B‐cell activation and immunoglobulin synthesis, documented by several in vitro studies, offers a pathogenetic explanation for these phenomena. This study shows that an anomalous B‐cell function contributes greatly to the morbidity of disease in LGL/NK‐PD, and points out the utility of investigating the LGL/NK cell system in patients with autoimmune pathologic characteristics of unclear origin.