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

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 beta 2-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.

Clinicobiological, Immunophenotypic, and Molecular Characteristics of Monoclonal CD56−/+dim Chronic Natural Killer Cell Large Granular Lymphocytosis

“…In line with this hypothesis, one patient with CNKCL and hemolytic anemia, whose NK cells displayed cytotoxic activity against autologous erythrocytes has been previously reported 51 and anemia associated with CNKCL usually responds to cyclosporine A. 54,55 Irrespectively of the mechanism involved, it seems obvious that cytopenias occur as a consequence of peripheral destruction because they usually responded to corticosteroids and splenectomy and laboratorial evidence of hemolysis was a frequent finding.…”

Abnormal NK Cell Lymphocytosis Detected after Splenectomy: Association with Repeated Infections, Relapsing Neutropenia, and Persistent Polyclonal B-Cell Proliferation

“…The inverse relationship between the neutrophil and lymphocyte counts would support this hypothesis. Autoimmune phenomena and B-cell dysfunction also are frequently observed in patients with lymphoproliferative disorders of LGL [16], and NK cells produce B-cell growth factors able to both sustain proliferation of activated B-cells and induce B-cells to initiate immunoglobulin secretion [17,18]. This finding suggests a possible relationship between NK cell lymphocytosis and the polyclonal expansion of peripheral blood B-cells.…”

Hairy Cell Leukemia: An Elusive but Treatable Disease

“…For example, HCL may atypically present with cutaneous, visceral, bone, pleural, and meningeal involvement [22][23][24][25][26][27][28][29]. Polyclonal and monoclonal gammopathy have been reported in 3%-20% of patients and may be related to an associated plasma cell dyscrasia, lymphoma, or autoimmune disorder [30][31][32]. For reasons not yet elucidated, HCL may be associated with a variety of autoimmune disorders, most commonly vasculitis [25,[33][34][35][36][37][38][39].…”