Figure-18 Kidney damage, assessed by proteinuria was measured in NZB/NZW mice over 5 months. Untreated animals developed severe proteinuria, while methysergide-treated animals did not. Methysergide blocks formation of the vasoactive amine, 5-HT, and thus blocks a variety of inflammatory events, e.g. deposition of complexes, neutrophil infiltration of capillary walls and endothelial proliferation, all of which produce the glomerular pathology.

Figure-19 Factors that effect complex deposition include filtration and high blood pressure, both of which occur in the formation of ultrafiltrate in the renal glomerulus (1). Turbulence at curves or bifurcations of arteries (2) also favours deposition of immune complexes.

Figure-20 Endotoxin, injected into mice, increases vascular permeability and induces cell damage and release of DNA. The DNA can then become deposited (1) on the collagen of the glomerular basement membrane (GBM) in the kidney. Endotoxin can also induce a polyclonal stimulation of B cells, some of which produce autoantibodies such as anti-DNA and anti-IgG – the latter are known as rheumatoid factors (RFs). Anti-DNA antibody can then bind to the deposited DNA forming a local immune complex (2). RFs have a low affinity for monomeric IgG, but bind with high avidity to the assembled DNA-anti-DNA complex (3). Thus further immune complex formation occurs in situ.

Figure-21 The site of complex deposition in the kidney is dependent on the site of the complexes in the circulation. Large complexes become deposited on the glomerular basement membrane, while small complexes pass through the basement membrane and are seen on the epithelial side of the glomerulus.

Figure-22 Immune-complex disease is automatic in the NZB/NZW mouse and follows a class switch during early development, form IgM to IgG2a. The graphs show the proportions of anti-DNA antibodies of the IgM and IgG2a isotypes in females and males. Both the class switch and fatal renal disease occur earlier in the female mice of this strain.

Dr. MUSTAFA HASSAN LINJAWI