Broad alterations of self-reactive antibody-repertoires of plasma IgM and IgG in B-cell chronic lymphocytic leukemia (B-CLL) and B-CLL related target-restricted autoimmunity

B-cell chronic lymphocytic leukemia (B-CLL) is characterized by a malignant CD5(+) B-cell clone. The leukemic clone commonly expresses IgM antibodies exhibiting reactivity toward a wide range of self-antigens. However, B-CLL associated autoimmunity is typically restricted to self-antigens expressed by blood cells, and mediated by IgG autoantibodies of polyclonal origin. In the present study, we addressed the question whether self-reactive antibod y repertoires of plasma IgM and IgG are disturbed by monoclonal immunoglobu lins of B-CLL patients, and whether antibody repertoires of patients exhibi ting B-CLL associated target-restricted autoimmune disease (AID) differ fro m those of B-CLL patients without AID. We investigated antibody repertoires at a global level, using a technique of quantitative immunoblotting that a llows for the quantitative screening of antibody reactivities in complex an tibody mixtures toward a large panel of antigens derived from homologous ti ssue extracts, followed by multiparametric statistical analysis of the data . We demonstrate that self-reactive antibody repertoires of plasma IgM and IgG are broadly altered in patients with B-CLL, that alterations in self-re active antibody repertoires are not restricted to B-CLL patients exhibiting ADD, and that target-restricted autoimmunity in B-CLL patients is associat ed with altered antibody repertoires not restricted to the target organ. We conclude that monoclonal alterations of immunoglobulin production in B-CLL are associated with broad defects of self-reactive antibody repertoires. O ur observations suggest that the application of therapeutic IVIg preparatio ns might influence B-CLL by restoring normal self-reactive antibody reperto ires in plasma.