MRL mice show an age-related impairment of IgG aggregate removal from the circulation

Abstract

The fate of heat-aggregated human IgG (HAGG) was examined in young and old autoimmune MRL-lpr/lpr and MRL-+/+ mice and compared to BALB/c mice of different ages. Following iv injection of [125I] HAGG the older MRL-lpr/lpr and MRL-+/+ mice showed impaired hepatic and splenic uptake of this material. In addition the clearance rate of HAGG was significantly slower in the older MRL-lpr/lpr mice (t1/2 = 50 min) when compared to younger controls (t1/2 = 13 min) although this age-related retardation of clearance was not observed in the MRL-+/+ mice. No difference was seen in the clearance rate or organ uptake studies of the two age groups of BALB/c mice. Catabolic studies using trichloracetic acid suggested that the HAGG was catabolized to smaller fragments with time but not to such a great extent in the older diseased animals, again no age-related difference was seen in the BALB/c mice. Our studies suggest that with age both autoimmune strains of MRL mice show some saturation of the mononuclear phagocytic system (MPS) and that this process is more obvious in the MRL-lpr/lpr mice. MPS saturation may play a role in the pathogenesis of autoimmune disease in these mice.