What is the role of IgM antibodies in the pathophysiology of cold agglutinin disease?

Updated: Aug 28, 2018
  • Author: Salman Abdullah Aljubran, MD; Chief Editor: Michael A Kaliner, MD  more...
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In its classic presentation, with hemolytic anemia and Raynaud syndrome, cold agglutinin disease is usually idiopathic. As with most autoimmune diseases of a chronic nature, stimulated B lymphocytes begin to produce pathogenic antibodies against an antigen that is normally present in human tissue. In cold agglutinin disease, the antibody is an IgM, usually monoclonal, with kappa (κ) or lambda (λ) light chains. In chronic cold agglutinin disease, the antibody is usually directed against the I antigen on the membrane of normal adult RBCs.

Uncommonly, the antibody may be directed against only the i antigen found on fetal cord blood RBCs, which lack the mature I antigen; this has been reported in association with infectious mononucleosis. [27]

In a study of 78 patients, κ light-chain specificity was found in the majority of patients with chronic cold agglutinin disease or Waldenström macroglobulinemia, whereas two thirds of cold agglutinins found in patients with lymphomas had λ light-chain specificity. The type of light chain appears to correlate with the antigen specificity of the cold agglutinin. Fifty-eight percent of IgM/κ (usually κIII variable region subgroup) was anti-I, but 75% of IgM/λ had other antigen specificities. [11]

Antigen specificities of cold agglutinins other than the I/i system that have been described include those against Pr, M, P, and Lud and anti-Gd, anti-Fl, and anti-Sa. [7, 10, 13] Exclusive occurrence of κ chains has also been shown with some cold agglutinins. [6] Thus, benign and malignant cold agglutinins exhibit differences in their light chains and their specificities toward membrane antigens.

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