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10.1002/art.38888 http://scihub22266oqcxt.onion/10.1002/art.38888 C4264660!4264660!25306868     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=25306868&cmd=llinks): Failed to open stream: HTTP request failed! 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Vimentin is a dominant target of in situ humoral immunity in human lupus tubulointerstitial nephritis |pdf=|usr=}}{{25306868}} gab.com Text Vimentin is a dominant target of in situ humoral immunity in human lupus tubulointerstitial nephritis JO: Arthritis Rheumatol http://www.kidney.de/pget.php?&tw=1&pmid=25306868 #FOAvip Objective: In lupus nephritis (LuN), severe tubulointerstitial inflammation (TII) predicts progression to renal failure. Severe TII is associated with tertiary lymphoid neogenesis and in situ antigen-driven clonal B cell selection. The autoantigen(s) driving in situ B-cell selection in TII are not known. This study aimed to identify the dominant driving autoantigen(s). Methods: Single CD38+ or Ki-67+ B cells were laser captured from seven LuN diagnostic biopsies. Eighteen clonally expanded immunoglobulin heavy and light chain variable region pairs were cloned and expressed as monoclonal antibodies. Seven more antibodies were cloned from flow sorted CD38+ cells from an eighth biopsy. Antigen characterization was performed using a combination of confocal microscopy, ELISA, screening protoarrays, immunoprecipitation and mass spectrometry. Serum IgG titers to the dominant antigen were determined in 48 LuN and 35 non-nephritic lupus samples using purified antigen-coated arrays. Autoantigen expression was localized by immunohistochemistry and immunofluorescence on normal and LuN kidney. Results: Eleven of 25 antibodies reacted with cytoplasmic structures, four reacted with nuclei, and none with dsDNA. Vimentin was the only autoantigen identified by both mass spectrometry and by protoarray. Ten of the 11 anti-cytoplasmic TII antibodies directly bound vimentin. Vimentin was highly expressed by tubulointerstitial inflammatory cells, and tested TII antibodies preferentially bound inflamed tubulointerstitium. Finally, high-titers of serum anti-vimentin antibodies were associated with severe TII (p = 0.0001). Conclusion: Vimentin, an antigenic feature of inflammation, is a dominant autoantigen targeted in situ in LuN TII. This adaptive autoimmune response likely feeds forward to worsen TII and renal damage. Twit Text FOAVip Vimentin is a dominant target of in situ humoral immunity in human lupus tubulointerstitial nephritis ????Arthritis Rheumatol http://www.kidney.de/pget.php?&tw=1&pmid=25306868 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25306868 #FOAvip English Wikipedia <ref>{{Cite pmid|25306868}}</ref> Vimentin is a dominant target of in situ humoral immunity in human lupus tubulointerstitial nephritis #MMPMID25306868 Kinloch AJ; Chang A; Ko K; Dunand CJH; Henderson S; Maienschein-Cleine M; Kaverina N; Rovin B; Ferrer MS; Wolfgeher D; Liarski V; Haddon DJ; Utz PJ; Wilson PC; Clark MR Arthritis Rheumatol 2014[Dec]; 66 (12): 3359-70 PMID25306868show ga Objective: In lupus nephritis (LuN), severe tubulointerstitial inflammation (TII) predicts progression to renal failure. Severe TII is associated with tertiary lymphoid neogenesis and in situ antigen-driven clonal B cell selection. The autoantigen(s) driving in situ B-cell selection in TII are not known. This study aimed to identify the dominant driving autoantigen(s). Methods: Single CD38+ or Ki-67+ B cells were laser captured from seven LuN diagnostic biopsies. Eighteen clonally expanded immunoglobulin heavy and light chain variable region pairs were cloned and expressed as monoclonal antibodies. Seven more antibodies were cloned from flow sorted CD38+ cells from an eighth biopsy. Antigen characterization was performed using a combination of confocal microscopy, ELISA, screening protoarrays, immunoprecipitation and mass spectrometry. Serum IgG titers to the dominant antigen were determined in 48 LuN and 35 non-nephritic lupus samples using purified antigen-coated arrays. Autoantigen expression was localized by immunohistochemistry and immunofluorescence on normal and LuN kidney. Results: Eleven of 25 antibodies reacted with cytoplasmic structures, four reacted with nuclei, and none with dsDNA. Vimentin was the only autoantigen identified by both mass spectrometry and by protoarray. Ten of the 11 anti-cytoplasmic TII antibodies directly bound vimentin. Vimentin was highly expressed by tubulointerstitial inflammatory cells, and tested TII antibodies preferentially bound inflamed tubulointerstitium. Finally, high-titers of serum anti-vimentin antibodies were associated with severe TII (p = 0.0001). Conclusion: Vimentin, an antigenic feature of inflammation, is a dominant autoantigen targeted in situ in LuN TII. This adaptive autoimmune response likely feeds forward to worsen TII and renal damage. äVimentin is a dominant target of in situ humoral immunity in human lup(epmc).pdf DeepDyve Pubget Overpricing