Cold Agglutinin Disease in a Rhesus Macaque (Macaca mulatta)

Abstract

Cold agglutinin disease (CAD) is a condition involving anemia and its related symptoms; it is caused by autoantibodiesthat bind and agglutinate red blood cells in areas susceptible to hypothermia, such as extremities exposed to cold temperatures.CAD is rare, with 5 to 20 human cases per million individuals. In this report, we describe a case of CAD in a previouslyhealthy and experimentally naïve adult Indian rhesus macaque that was housed indoors and presented with blood in theurine. After our observations of hemoglobinuria and anemia led us to suspect CAD, we demonstrated that the macaque’sblood agglutinated at reduced temperatures. We also noticed that the provision of cold foraging treats triggered episodes ofhemoglobinuria. Further investigation revealed that serum from the macaque agglutinated RBCs in vitro with high thermalamplitude (at or below 30 °C) and had an antibody titer of 8 to 32. The serum contained autoantibodies of the immunoglobulinM (IgM) isotype; agglutinins of the IgG isotype were not detected. The cold-dependent IgM autoantibodies in the serum fromthe affected macaque reacted against a common RBC antigen because RBCs collected from other macaques were bound andagglutinated by the affected animal’s IgM under cold conditions. This in vitro binding activity was reversible when the testtemperature was returned to normal body temperature (37 °C). These findings demonstrated cold-dependent RBC-specific IgMagglutinins and led us to a diagnosis of CAD. This is the first documented case of spontaneous CAD in a rhesus macaque.