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 antibody repertoires of plasma IgM and IgG are disturbed by monoclonal immunoglobulins of B-CLL patients, and whether antibody repertoires of patients exhibiting B-CLL associated target-restricted autoimmune disease (AID) differ from those of B-CLL patients without AID. We investigated antibody repertoires at a global level, using a technique of quantitative immunoblotting that allows for the quantitative screening of antibody reactivities in complex antibody mixtures toward a large panel of antigens derived from homologous tissue 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-reactive antibody repertoires are not restricted to B-CLL patients exhibiting AID, and that target-restricted autoimmunity in B-CLL patients is associated 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. Our observations suggest that the application of therapeutic IVIg preparations might influence B-CLL by restoring normal self-reactive antibody repertoires in plasma.
Stahl
D
D
INSERM U430, Université Pierre et Marie Curie, Hôpital Broussais, Paris, France. stahld@uni-muenster.de
Lacroix-Desmazes
S
S
Sibrowski
W
W
Kazatchkine
M D
MD
Kaveri
S V
SV
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood / Q000145:classification; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000150:complications / Q000276:immunology*; D008297:Male; D008875:Middle Aged
D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M