Related Experiment Videos
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.
Insights
Systemic lupus erythematosus (SLE) in mice can cause two vascular lesions: necrotizing polyarteritis (NPA) linked to high autoantibodies and immune complexes, and degenerative vascular disease (DVD) associated with sustained low immune complexes.
Area of Science:
- Immunology
- Pathology
- Rheumatology
Background:
- Systemic lupus erythematosus (SLE) in mice presents with distinct vascular pathologies.
- Two main types include necrotizing polyarteritis (NPA) and degenerative vascular disease (DVD).
- These lesions differ in incidence, pathology, and associated autoimmune profiles across mouse strains.
Purpose of the Study:
- To differentiate the pathogenic mechanisms of NPA and DVD in murine SLE models.
- To investigate the role of autoantibodies and immune complexes in vascular damage.
- To correlate specific autoantibody profiles with distinct vascular lesion types.
Main Methods:
- Comparative analysis of vascular lesions in MRL/l and (NZW x BXSB)F1 (WBF1) male mice.
- Serological analysis of autoantibody levels and circulating immune complexes.
- Characterization of immune complex composition (anti-DNA, anti-gp70).
- Immunoglobulin elution from affected kidneys and hearts.
- Assessment of inflammatory response via reverse passive Arthus reaction.
Main Results:
- NPA in MRL/l mice showed high autoantibodies, large immune complexes (7S-19S) with anti-DNA, and kidney deposition.
- DVD in WBF1 mice exhibited early, low-magnitude autoantibodies, minimal detectable complexes with anti-gp70, and significant immunoglobulin deposition in hearts.
- DVD hearts had 10x more eluted immunoglobulins than NPA.
- DVD pathogenesis was independent of IgG1 deposition or defective inflammatory response.
Conclusions:
- NPA develops secondary to high autoantibody levels and resultant immune complexes.
- DVD is associated with sustained low levels of circulating immune complexes, primarily anti-gp70.
- Distinct autoantibody profiles and immune complex dynamics drive different vascular pathologies in SLE.