Heat shock proteins (HSP) are a family of ubiquitous and phylogenically highly conserved proteins [1]. Autoreactivity to HSP is often associated with autoimmune pathology. Previous studies have demonstrated the presence of autoantibodies to the HSP90 in a significant proportion of patients with systemic lupus. Anti-HSP90 autoantibodies of the IgG class were detected in approximately 50% [2] and 26% [3] and of IgM class in 35% [3] of unselected patients with SLE. The presence of high titre anti-HSP90 autoantibodies was found to correlate with renal involvement and low C3 levels [3]. Although HSP90 is an intracytoplasmic protein, surface expression of HSP90 on peripheral blood mononuclear cells was found in approximately 25% of the patients with systemic lupus erythematosus (SLE) during active disease [4]. It has been shown that the increased expression of HSP90 is due to the enhanced transcription of the HSP90a gene [5]. Although these results indicate an association of anti-HSP90 autoreactivity with SLE, no direct involvement of HSP90 and anti-HSP90 antibodies in the pathogenesis of the disease has been proven. Moreover, normal human IgG (represented by pooled preparation for i.v. use -IVIg) has been found to contain considerable amounts of low-affinity anti-HSP90 natural autoantibodies [6].The aim of the present study was to investigate the role of HSP90 as an autoantigen in the renal injury in SLE by looking for HSP90 containing immune complexes in kidney biopsies of lupus patients. Since the most probable cause for such deposits is the presence of high titre anti-HSP90 autoantibodies in the sera of SLE patients and considering the fact that natural anti-HSP90 autoantibodies are found also in healthy individuals, we examined the possibility of using this autoreactivity as a model to study the relation between natural and disease-associated autoantibodies. 169Lupus-specific kidney deposits of HSP90 are associated with altered IgG idiotypic interactions of anti-HSP90 autoantibodies SUMMARYPrevious studies have shown that autoantibodies to heat shock protein 90 (HSP90) are elevated in a significant proportion of patients with systemic lupus erythematosus (SLE) who are more likely to have renal disease and a low C3 level. Using samples from 24 patients, we searched for glomerular deposits of HSP90 in renal biopsy specimens from seven patients with lupus nephritis and 17 cases of glomerulonephritis from patients without SLE. Positive glomerular immunofluorescent staining for HSP90 was observed in six of seven cases of SLE and positive tubular staining in two of seven SLE patients. The staining for HSP90 was granular in nature and was located in subepithelial, subendothelial and mesangial areas. None of the non-SLE renal biopsies revealed positive staining for HSP90 deposition. Further we showed the presence of anti-HSP90 IgG autoantibodies in IgG from sera of patients with SLE as well as in normal human IgG (IVIg). In normal IgG this autoreactivity could be adsorbed almost completely on F(ab¢) 2 fragments from the...

There is already a considerable amount of evidence suggesting that fibronectin (Fn) plays an important role in the pathogenic process in some forms of glomerulonephritis (GN). It has been postulated that Fn may participate in the progression or regression of glomerular diseases. The Fn is presented in the kidney as a normal component of the mesangium, and it is increased in the expanded mesangium in various forms of GN. This paper reports our efforts to investigate the role of Fn in plasma and kidney in patients with GN. Using monoclonal antibodies against human Fn in the ELISA and immunohistoperoxidase techniques to evaluate Fn, we investigated its quantity in connection with clinical state and morphological findings. We studied 93 patients with GN and 26 renal biopsies. The patients with active forms of mesangial proliferative, membranoproliferative and membranous GN showed increased plasma Fn, and the highest levels were in patients with nephrotic syndrome. Increased tissue Fn correlated with mesangial expansion and with IgG and C3 deposits. We speculate on possible mechanisms of the involvement of Fn in human chronic GN.

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