Analysis of vascular lesions in murine SLE. I. Association with serologic abnormalities.

Abstract

In murine SLE, two different vascular lesions can develop. A necrotizing polyarteritis (NPA), exclusively found in MRL/I mice, is characterized by a dense infiltration of PMN and fibrinoid necrosis of the arterial wall. The second, a degenerative vascular lesion, occurs in a low incidence in all SLE mice, except the (NZW X BXSB)F1 (WBF1) male, in which its incidence is 100%. This lesion shows subendothelial deposits of immunoglobulins with minimal or no inflammatory or proliferative reaction. This degenerative vascular disease (DVD) is predominantly localized in the coronary arteries and is highly correlated with myocardial infarction. Serologic analysis revealed that NPA in MRL/I mice was associated with relatively late development of high levels of autoantibodies and circulating immune complexes; DVD in WBF1 mice was associated with an early onset of autoantibody production of a low magnitude that gave rise to a persistent low level of circulating immune complexes. Characterization of circulating immune complexes in MRL/I mice showed these complexes were mainly of intermediate size (7S-19S) and contained predominantly anti-DNA antibodies. In WBF1 mice, complexes were barely detectable and contained mostly anti-gp70 antibodies. Elution of kidneys showed that the major antibody deposited in MRL/I mice has an anti-DNA specificity, whereas in WBF1 animals, the major antibody was anti-gp70. Furthermore, a 10 times greater amount of immunoglobulins could be eluted from WBF1 hearts with DVD than from MRL/I and BXSB hearts. Additionally, we found that the lack of an inflammatory reaction in DVD was not because of a preferential deposition of noncomplement-fixing IgG1 antibodies nor could it be related to a defective inflammatory response, because WBF1 mice had an undiminished reverse passive Arthus reaction throughout their lives. It is concluded that NPA develops secondary to high levels of autoantibodies with a concomitant rise in immune complexes, whereas DVD is associated with sustained low levels of circulating immune complexes.