Cold-reactive autoantibodies may be encountered in serologic testing. Cold autoantibodies are generally not clinically significant but they can cause difficulties during ABO/Rh typing and antibody detection.
Benign cold autoantibodies are IgM immunoglobulins present in the plasma at 4°C. They have been known to react at room temperature, on occasion, and can activate complement as well. These autoantibodies usually have a low titer; typically less than 1:64. Common benign autoantibodies include Anti-I, Anti-i, and Anti-IH.
Pathologic cold autoantibodies are known to react at much broader thermal ranges. Antibodies that cause disease usually bind to red cell antigens at 30-32°C. These antibodies are found in cold hemagglutinin disease (often secondary to infection) and in paroxysmal cold hemoglobinuria (PCH).