J. J. Weening

Expression of HLA-DR antigens on peripheral blood T lymphocytes and renal graft tubular epithelial cells in association with rejecion

Since the expression of HLA-DR antigens on peripheral blood T lymphocytes and renal graft tubular epithelial cells may be associated with immunological stimulation, we investigated the expression of these antigens on blood T lymphocytes and graft tubular epithelium in 84 renal transplant patients. Peripheral blood T lymphocytes were monitored by flow cytometry during the first 3 months after transplantation. Since the DR+ lymphocytes were selected by a double-labeling technique used for the Leu2a phenotype, the majority of the DR+ lymphocytes were also Leu2a+ with a small percentage of unidentified Leu2a- lymphocytes. Forty-one patients were treated with cyclosporine (CsA) and 43 with azathioprine (Aza), while both groups received low-dose steroids. Frozen sections of 57 renal biopsies from 43 patients (21 on CsA and 22 on Aza) were stained for HLA-DR antigens. In the Aza group, clinical rejection episodes correlated with an increased percentage of DR+ peripheral lymphocytes (P = 0.0005), and the expression of DR antigens on graft epithelial cells (P less than 0.001). In the CsA group, no relation between the expression of DR antigens on blood lymphocytes and clinical rejection episodes was evident, and the correlation between tubular DR staining and clinical rejection episodes was weaker than in the Aza group (P = 0.03). In both the Aza and CsA group, an increase in DR+ peripheral lymphocytes correlated with positive staining of the renal tubular cells for HLA-DR antigens (P less than 0.001).

Antigenic specificities of glomerular-bound autoantibodies in membranous glomerulopathy induced by mercuric chloride.

The present study describes the development of membranous glomerulopathy (MGP) with high proteinuria in DZB rats exposed to mercuric chloride (HgCl2). IgG1 and IgG2a antibodies, eluted from glomeruli with subepithelial immune deposits, bind to the interface of the GBM and epithelial cells. High reactivity to GBM was demonstrated by ELISA and Western blotting, which could be absorbed for 30% by laminin or laminin-associated extracellular matrix components. No reactivity was found with type IV collagen, fibronectin, heparan sulfate proteoglycans, or tubular brush border antigens. Absorption to GBM removed the reactivity to renal antigens. Passively transferred eluted antibodies bind in a predominantly linear pattern along the GBM, causing focal ultrastructural transformations of the podocytes. These results suggest that this type of HgCl2-induced MGP, associated with epithelial cell injury and proteinuria, is caused by autoantibodies to basement membrane components which are located at the epithelial cell-basement membrane interface and may be involved in cell-matrix binding.

Pathobiology of focal sclerosis.

This paper briefly reviews recent experimental data derived from work in animals and cell cultures that have increased our understanding of the pathobiologic pathways leading to focal sclerosis. These pathways include glomerular visceral epithelial cell damage, leukocyte infiltration, hyperplasia and matrix accumulation in the mesangium, and endothelial injury.

Perivascular deposits of IgM in the skin of transplant recipients during active cytomegalovirus infections. Correlation with IgM rheumatoid factors and IgM immune complexes.

Skin biopsies from 30 renal transplant patients were investigated for cellular infiltrates and deposits of IgM, IgA, IgG, C3, and C5–9 neoantigen. Granular perivascular deposits of IgM were detected in biopsies of 8 of 14 patients during active cytomegalovirus (CMV) infections and in none of 16 controls. In 5 biopsies, the IgM deposits were accompanied by little or no IgG, IgA, or C, while in 3 biopsies definite C3 deposits were present. One of the biopsies with C3 deposits also had C5–9 deposits and another had C5–9 and IgA deposits. Three monoclonal antibodies failed to detect early or late nuclear antigens of CMV in the deposits. These deposits were not associated with clinically evident manifestations of vasculitis. A strong correlation was found between IgM deposits in the skin and IgM circulating immune complexes (CIC) and also IgM rheumatoid factor (RF). The deposition of IgM was not more frequent in primary than in secondary CMV infections, and it did not correlate with the production of IgM antibodies that were specific for CMV antigens.