Lupus nephritis: lessons from experimental animal models.

Lupus nephritis is a frequent and severe complication of SLE. In the last decades, animal models for SLE have been studied widely to investigate the immunopathology of this autoimmune disease because abnormalities can be studied and manipulated before clinical signs of the disease become apparent. In this review an overview is given of our current knowledge on the development of lupus nephritis, as derived from animal models, and a hypothetical pathway for the development of lupus nephritis is postulated.

Synergistic effects of anti-gp330 and anti-dipeptidyl peptidase type IV antibodies in the induction of glomerular damage.

Passive Heymann nephritis (PHN) in the rat is induced by the administration of heterologous antibodies to renal tubular epithelium (RTE). The nephritogenic capacity of anti-RTE resides primarily in the antibody fraction directed against a 330-kD glycoprotein (gp330). However, monospecific anti-gp330 antibodies are less nephritogenic than anti-RTE antibodies.

Redistribution of glomerular dipeptidyl peptidase type IV in experimental lupus nephritis. Demonstration of decreased enzyme activity at the ultrastructural level.

Background: In murine chronic graft-versus-host disease, an experimental model for lupus nephritis, autoantibodies against renal tubular epithelium can be found. Part of these antibodies are directed against a constituent of renal tubular epithelium, the enzyme Dipeptidyl peptidase IV (DPP IV). DPP IV is present on the cell membrane of glomerular epithelial and endothelial cells, and plays an important role in cell-extracellular matrix interactions.

Gender-related influences on the development of chronic graft-versus-host disease-induced experimental lupus nephritis.

Autoimmune diseases are far more common in women than in men. In the incidence of systemic lupus erythematosus (SLE), the female-to-male ratio is as high as 10:1. This suggests that sex hormones may play a fundamental role in determining the susceptibility to these diseases.

Epitope specificity of anti-gp330 autoantibodies determines the development of proteinuria in active Heymann nephritis.

In active Heymann nephritis, an experimental autoimmune disease in the rat, gp330 is regarded as the main antigenic target. Immunization with detergent-solubilized renal tubular epithelium (RTE-DOC) has been shown to be less nephritogenic than immunization with crude RTE. In this study immunization with either crude RTE or affinity-purified gp330 did, but immunization with RTE-DOC did not induce proteinuria.

Antigen size influences the type of glomerular pathology in chronic serum sickness.

Chronic serum sickness was induced in four groups of Wistar rats by immunization with BSA, cationized BSA (cBSA), human IgG (HuIgG), or human IgM (HuIgM), followed by repeated intraperitoneal (i.p.) injection of the antigen used, to study the effect of the characteristics of an antigen on renal immunopathology.

A histologic study of the extracellular matrix during the development of glomerulosclerosis in murine chronic graft-versus-host disease.

The development of glomerulosclerosis was studied in murine chronic graft-versus-host disease (GvHD), which is a model for human systemic lupus erythematosus. The authors investigated the distribution patterns of six components of the extracellular matrix (ECM), i.e.

Myocardial creatine kinase-MB concentration in normal and explanted human hearts and released from hearts of patients with acute myocardial infarction.

Using an enzyme immunoassay of creatine kinase (CK)-MB concentration commercially available for diagnosis of acute myocardial infarction (AMI), we studied CK-MB concentrations in myocardium of subjects who died from noncardiac causes and in cardiac explants of patients with either coronary heart disease or cardiomyopathy who underwent cardiac transplantation. Secondly, CK-MB concentrations were measured in serial plasma samples of 93 patients with AMI. By calculation of cumulatively released amounts of CK-MB and cumulatively released activities of CK, aspartate aminotransferase (AST) and alpha-hydroxybutyrate dehydrogenase (HBDH), we obtained values of the proportions in which these quantities were released from the myocardium.

Renal immunopathology in murine host-versus-graft disease.

BALB/c mice neonatally injected with 1 x 10(8) (A/J x BALB/c)F1 hybrid spleen cells develop polyclonal B cell activation and autoimmune features as a consequence of a host-versus-graft (HVG) reaction. In this study, we first analyzed the time-course development of the renal lesions in HVG mice. From week 2 to week 6, linear deposits of IgG were observed by immunofluorescence along the glomerular capillary walls.

T-cell receptors and ICAM-1 expression in renal allografts during rejection.

Sixty-two biopsies taken from 38 kidney grafts were studied for 15 histological and 10 immunohistological parameters. The biopsies were divided into three groups, according to the clinical diagnosis at the time they were performed: group 1, rejection (n = 43); group 2, other causes of dysfunction (n = 10); and group 3, stable function (n = 9). Histological signs of acute rejection included diffuse interstitial infiltrate, tubular basement membrane damage, mononuclear leukocyte infiltration, and congestion of the peritubular capillaries.

Expression of HLA-DQ antigens in the small-intestinal mucosa of patients with coeliac disease.

Studies at the DNA and product level of B-cell lines of coeliac patients have shown a strong association between coeliac disease and the HLA-DQ alpha 2.3 and HLA-DQ beta 2.7 alleles.

Susceptibility to the induction of either autoimmunity or immunosuppression by mercuric chloride is related to the major histocompatibility complex class II haplotype.

Mercuric chloride (HgCl2) induces in Brown Norway rats a CD4+ T lymphocyte-dependent systemic autoimmune syndrome, involving synthesis of anti-glomerular basement membrane autoantibodies and development of proteinuria. Lewis rats are resistant to HgCl2-induced autoantibody production and, in contrast, develop immunosuppression, mediated by CD8+ T lymphocytes. In the present study, genetic requirements governing autoreactivity or immunosuppression in response to HgCl2 were further explored.

Helicobacter pylori infection of gastric mucin cell metaplasia: the duodenum revisited.

The histological material of 158 Billroth II gastrectomy specimens, used for a former study that established a relationship between duodenal ulcers and the presence of gastric metaplastic epithelium in the duodenal bulb, was reinvestigated for the presence of Helicobacter pylori. The results show that in all duodenal ulcer patients with gastric mucin cell metaplasia H. pylori colonized the metaplastic epithelium accompanied by an inflammatory response.

Imaging of acute myocardial infarction in pigs with Indium-111 monoclonal antimyosin scintigraphy and MRI.

Indium-111 antimyosin F(ab')2 was used in a series of scintigraphic studies on experimentally induced myocardial infarctions in pigs. Antimyosin distribution recorded by planar images of in vivo pigs and by single photon emission computed tomography (SPECT) of excised hearts delineated areas of myocardial necrosis if infarct volume exceeded 3.3 cm3.

Pathogenesis of experimental lupus nephritis: a role for anti-basement membrane and anti-tubular brush border antibodies in murine chronic graft-versus-host disease.

The pathogenesis of renal involvement was studied in murine chronic graft-versus-host disease (GVHD), which is a model for human systemic lupus erythematosus. GVHD was induced by four i.v.

Thymocytes reacting with heterologous antibodies against GP 330 in autologous immune complex glomerulopathy (AICG) in the rat. The relation between susceptibility for AICG and anti-GP 330-binding thymocytes.

Autologous immune complex glomerulopathy (AICG) is induced by immunizing rats with a crude brushborder fraction of rat kidney tubules (Fx1A) or with the purified GP 330 antigen. In these animals, anti-brushborder antibodies develop, leading to subepithelial immune complexes along the glomerular capillary wall. In rats with AICG, thymocytes sensitized against Fx1A as well as thymocytes recognizing anti-Fx1A are present.