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Anti-erythrocyte antibodies which appear in the sera of patients with auto-immune hemolytic anemia frequently recognize carbohydrate auto-antigens. Most of cold agglutinins are known to recognize the Ii-antigens, and Donath-Landsteiner antibodies which appear in patients with paroxismal cold hemoglobinuria are almost exclusively directed to the P-antigen. These carbohydrate auto-antigens are strongly expressed in various tissues and organs other than erythrocytes, and behave as differentiation- or developmental-antigens, in both humans and mice. The study of nucleotide sequences of human and murine anti-Ii antibodies shows that these antibodies share a highly homologous antigen-binding site in their VH regions. These results indicate that the carbohydrate auto-antigens in autoimmune hemolytic anemia are evolutionally conserved developmental antigens, and suggest that the immunoglobulin genes which encode variable regions of the auto-antibodies directed to these antigens are also conserved evolutionally.
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