The pathologic significance of the immunoglobulins expressed by chronic lymphocytic leukemia B-cells in the development of autoimmune hemolytic anemia.
The increased number of CD5+ B-cells in some human autoimmune diseases, the frequent commitment of CD5+ B-cells to the production of natural autoantibodies, and the apparent involvement of these cells in the pathogenesis of the autoimmune hemolytic anemia (AIHA) in certain mouse models suggests a causal relationship between the CD5+ chronic lymphocytic leukemia (CLL) B-cell and the AIHA which frequently develops in this malignant disorder. In support of this conclusion is our recent finding that the VH region gene repertoire of the leukemic B-cells from CLL patients with AIHA is rather biased and characterised by the over-representation of the 51p1 VH gene. On the other hand, it appears relatively certain that the pathogenic anti-erythrocyte antibodies in CLL patients with AIHA are produced by remnant normal B-cells, and that the antibodies expressed by the leukemic CD5+ B-cells do not directly bind red blood cells (RBC). Of interest, the antibodies produced by the leukemic B-cells from CLL patients with AIHA might have in common rheumatoid factor (RF) activity. These data indicate that the antibodies produced by the leukemic B-cells from CLL patients with AIHA are not directly involved in red blood cell destruction, but may be involved in the induction or amplification of a polyclonal anti-RBC response. Finally, we discuss the possible clinical implications of our finding that CLL patients with leukemic cells expressing the 51p1 VH gene may be at a higher risk to develop autoimmune hemolytic anemia.
Efremov
D G
DG
International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
Ivanovski
M
M
Burrone
O R
OR
D000744:Anemia, Hemolytic, Autoimmune / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007136:Immunoglobulins / Q000096:biosynthesis*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000150:complications* / Q000276:immunology / Q000473:pathology
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007136:Immunoglobulins