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- Title
Functional characterization of cytokine autoantibodies in chronic renal failure patients.
- Authors
Sunder-Plassmann, Gere; Kapiotis, Stelio; Gasche, Christoph; Klaar, Ursula; Mai, Brigitte
- Abstract
We have recently reported on an increase of IL-1α and lL-6 autoantibodies in patients maintained on chronic hemodialysis treatment. The aim of the present study was to evaluate functional properties of these autoantibodies. Serum samples of more then 500 chronic renal failure patients with and without replacement therapy were screened for the presence of IL-1α and IL-6 autoantibodies by second antibody precipitation. The neutralizing capacity of IL-1α autoantibody serum was studied by immunofluorescence flow cytometry analysis of IL-1α induced expression of E-selectin (ELAM-1, CD62e) on HUVEC (human umbilical vein endothelial cells). Results of these inhibition studies were confirmed with IgG preparations from antibody positive sera, purified by affinity chromatography. Functional studies on IL-6-dependent B9 cell proliferation were performed with lL-6 autoantibody positive sera, and quantitated with the colorimetric MTT assay. IL-1α induced expression of E-selectin on HUVEC (considered 100% positive cells) was inhibited by each IL-1α autoantibody positive serum sample (N = 13; anti-IL-1α activity: 7.62 to 57.52% binding). Inhibition of E-selectin expression by IL-1α autoantibodies ranged from 0.11 to 80.22% positive cells (0.15 to 92.31% mean fluorescence intensity). A strong correlation of E-selectin expression with IL-1α autoantibody concentration was observed (P < 0.005). Furthermore. IgG eluates from autoantibody positive patients inhibited E-selectin expression to 41.0 ± 23.1% positive cells if compared with 83.7 ± 5.7% positive cells of the IgG depleted serum samples. IgG eluates and IgG depleted sera derived from anti-IL-1α negative serum samples had no major influence on E-selectin expression (79.9 ± 28.5% and 77.9 ± 16.8%, respectively). IL-6 autoantibody sera (N = 11; anti-IL-6 activity: 5.85 to 53.28% binding) had no inhibitory effect on B9 cell proliferation (1:1000: 102.1 ± 7.1%. 1:100: 106.8 ± 9.2%. 1:10: 146.2 ± 26.6% proliferation). We conclude that IL-1α autoantibodies in chronic renal failure patients deliver inhibitory activity on IL-1α, at least in vitro. IL-6 autoantibodies were not found to influence IL-6 dependent proliferation of B9 cells.
- Subjects
CYTOKINES; AUTOANTIBODIES; TREATMENT of chronic kidney failure; HEMODIALYSIS; SELECTINS; IMMUNOFLUORESCENCE
- Publication
Kidney International, 1994, Vol 45, Issue 5, p1484
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1038/ki.1994.193