Autoantibodies present an interesting problem, both in their clinical manifestations and in the difficulty of laboratory detection and identification. They may be either the warm or cold type and may be complete or incomplete.

Warm autoantibodies react at body temperature and are most often of the incomplete type. They comprise about 70% of autoantibodies. They may be idiopathic or secondary to certain diseases. The main disease categories responsible are leukemias and lymphomas (particularly chronic lymphocytic leukemia and Hodgkin’s disease); collagen diseases (especially disseminated lupus); and, uncommonly, a variety of other diseases, including cirrhosis and extensive carcinoma. Results of the direct Coombs’ test are usually but notalways positive, both in the “idiopathic acquired” and the secondary autoimmune hemolytic anemias. In one report, 2%-4% of patients with autoimmune hemolytic anemia had a negative direct Coombs’ test result. If the Coombs’ test result is negative, demonstration of warm autoantibodies is very difficult, often impossible.

Cold autoantibodies react at 4°C-20°C and are found so frequently in normal persons that titers up to 1:32 are considered normal. Theyare hemagglutinating and are believed to be due to infection by organisms having antigenic groups similar to some of those on the RBCs. These antibodies behave mostly as bivalent types and require complement for reaction. In normally lowtiter they need refrigerator temperatures to attack RBCs. In response to a considerable number of diseases, these cold agglutinins are found in high titer, sometimes very high, and may then attack RBCs at temperatures approaching body levels, causing hemolytic anemia. High-titer cold agglutinins may befound in nonbacterial infections, especially mycoplasma pneumonia (primary atypical pneumonia), influenza, and infectious mononucleosis; in collagen diseases, including rheumatoid arthritis; in malignant lymphomas; and occasionally in cirrhosis. Fortunately, even when cold autoantibodies are present in high titer there usually is no trouble, and generally only very high titers are associated with in vivo erythrocyte agglutination or hemolytic anemia. This is not always true, however. The direct Coombs’ test result is usually negative. When cold agglutinin studies are ordered, an indirect Coombs’ test is generally done, with the first stage being incubation of RBCs and the patient’s serum at 4°C-10°C.