Autoimmune Cytopenias in Chronic Lymphocytic Leukemia

Figure 1

Four main hypotheses of the CLL-associated autoimmune disorders pathogenesis. (1) CLL B-cells may act as either antigen presenting cells and processing cells of red blood cells (RBCs), thus inducing a T-cell response and, in turn, the activation of resting B-cells with the production of polyclonal antibodies against erythrocytes and, ultimately, hemolysis. (2) CLL B-cells may more rarely act as effector cells secreting pathological monoclonal autoantibodies. This is thought to happen in cold agglutinin disease (CAD), hepatitis C virus (HCV)-related cryoglobulins, and paraneoplastic pemphigus. (3) Autoantigens may stimulate B-CLL cells by means of their polyreactive B cell receptor (BCR). (4) Inhibitory cytokines, such as interleukin (IL)-6, IL-10, tumor necrosis factor (TNF), and tumor growth factor (TGF)-β, may be produced by B-CLL cells resulting in the loss of tolerance.