What is 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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Cold agglutinins, or cold autoantibodies, occur naturally in nearly all individuals. These natural cold autoantibodies occur at low titers, less than 1:64 measured at 4°C, and have no activity at higher temperatures. Pathologic cold agglutinins occur at titers over 1:1000 and react at 28-31°C and sometimes at 37°C.

Cold agglutinin disease usually results from the production of a specific IgM antibody directed against the I/i antigens (precursors of the ABH and Lewis blood group substances) on red blood cells (RBCs). Cold agglutinins commonly have variable heavy-chain regions encoded by VH, with a distinct idiotype identified by the 9G4 rat murine monoclonal antibody. [4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20]

Because the I antigen is not activated until after birth, anti-i autoantibodies predominantly agglutinate neonatal RBCs, and anti-I autoantibodies predominantly agglutinate adult RBCs.

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