A 37 year old woman with extravascular hemolytic anemia had a positive Monospot test associated with positive antiglobulin and anticomplement Coombs' tests, cold agglutinins and warm autoantibodies. IgG-kappa (κ) antibodies, which reacted with all panel red cells at 37 °C, were eluted from her circulating red cells. However, neither immunoglobulins nor C3 was detected after her serum was adsorbed with heterologous red cell stroma at 37 °C and eluted at the same temperature in glycine buffer. In contrast, IgM-κ and IgM-Iambda (λ), IgG3-κ, IgG4-λ, IgA-λ and C3 were eluted at 37 °C from heterologous red cell stroma after adsorption with her serum at 0 °C. Thus, antibodies of several types, which were present in the patient's serum, reacted optimally with red cell antigens at low temperature. Cold-reactive IgG3-κ antibodies, which were also capable of interacting with red cells at 37 °C, probably accounted for the IgG-κ antibodies eluted from the patient's circulating red cells. The patient's serum C4 titers were decreased, with low normal to moderately depressed C3 and low normal C5, indicating that the anti-red cell IgM and/or IgG3-κ antibodies probably fixed complement. A localized cold stress test resulted in a transient increase in plasma hemoglobin and a decrease in serum C3 titer. These findings, and the beneficial clinical response obtained with small doses of prednisone, suggest that both the cold-reactive antibodies and the IgG-κ on circulating red cells were pathophysiologically significant. This is the first report of a patient with multiple red cell autoantibodies in whom serum complement component titers were determined in conjunction with characterization of the anti-red cell immunoglobulins. Subclinical infectious mononucleosis may have preceded the prolonged hemolytic episode. Clinical evidence of systemic lupus erythematosus has not appeared.
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