A cold autoagglutinin will usually have specificity for which antigen?

• A. I antigen
• B. Ii antigen
• C. P antigen
• D. M antigen

Answer: (A)

Cold autoantibodies are typically IgM that bind red cells at low temperatures and fix complement, causing agglutination. The most common target is the I antigen on red cells, so anti-I is the classic cold agglutinin associated with cold agglutinin disease. The i antigen is the fetal form and anti-i is more often linked with other associations, not the usual cold agglutinin pattern. P antigen is associated with a different biphasic hemolysin found in paroxysmal cold hemoglobinuria, not the common cold agglutinin response, and M antigen is not a frequent target in this scenario. Thus, the I antigen is the usual specificity.