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10.1002/art.38888 http://scihub22266oqcxt.onion/10.1002/art.38888 C4264660!4264660 !25306868     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\25306868 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Arthritis+Rheumatol 2014 ; 66 (12 ): 3359-70 Nephropedia Template TP {{tp|p=25306868 |t=2014. 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 (LN), 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 was undertaken to identify the dominant driving autoantigen(s). METHODS: Single CD38+ or Ki-67+ B cells were laser captured from 7 biopsy specimens that were diagnostic for LN. 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 specimen. Antigen characterization was performed using a combination of confocal microscopy, enzyme-linked immunosorbent assay, screening protoarrays, immunoprecipitation, and mass spectrometry. Serum IgG titers to the dominant antigen in 48 LN and 35 non-nephritic lupus samples were determined using purified antigen-coated arrays. Autoantigen expression on normal and LN kidney was localized by immunohistochemistry and immunofluorescence. RESULTS: Eleven of 25 antibodies reacted with cytoplasmic structures, 4 reacted with nuclei, and none reacted with double-stranded DNA. Vimentin was the only autoantigen identified by both mass spectrometry and protoarray. Ten of the 11 anticytoplasmic TII antibodies directly bound vimentin. Vimentin was highly expressed by tubulointerstitial inflammatory cells, and the TII antibodies tested preferentially bound inflamed tubulointerstitium. Finally, high titers of serum antivimentin antibodies were associated with severe TII (P = 0.0001). CONCLUSION: Vimentin, an antigenic feature of inflammation, is a dominant autoantigen targeted in situ in LN 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 ; Henry Dunand CJ ; Henderson S ; Maienschein-Cline M ; Kaverina N ; Rovin BH ; Salgado Ferrer M ; Wolfgeher D ; Liarski V ; Haddon DJ ; Utz PJ ; Wilson PC ; Clark MR Arthritis Rheumatol 2014[Dec]; 66 (12 ): 3359-70 PMID25306868 show ga OBJECTIVE: In lupus nephritis (LN), 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 was undertaken to identify the dominant driving autoantigen(s). METHODS: Single CD38+ or Ki-67+ B cells were laser captured from 7 biopsy specimens that were diagnostic for LN. 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 specimen. Antigen characterization was performed using a combination of confocal microscopy, enzyme-linked immunosorbent assay, screening protoarrays, immunoprecipitation, and mass spectrometry. Serum IgG titers to the dominant antigen in 48 LN and 35 non-nephritic lupus samples were determined using purified antigen-coated arrays. Autoantigen expression on normal and LN kidney was localized by immunohistochemistry and immunofluorescence. RESULTS: Eleven of 25 antibodies reacted with cytoplasmic structures, 4 reacted with nuclei, and none reacted with double-stranded DNA. Vimentin was the only autoantigen identified by both mass spectrometry and protoarray. Ten of the 11 anticytoplasmic TII antibodies directly bound vimentin. Vimentin was highly expressed by tubulointerstitial inflammatory cells, and the TII antibodies tested preferentially bound inflamed tubulointerstitium. Finally, high titers of serum antivimentin antibodies were associated with severe TII (P = 0.0001). CONCLUSION: Vimentin, an antigenic feature of inflammation, is a dominant autoantigen targeted in situ in LN TII. This adaptive autoimmune response likely feeds forward to worsen TII and renal damage. |Adolescent [MESH] |Adult [MESH] |Autoantibodies/*immunology [MESH] |Autoantigens/*immunology [MESH] |Biopsy [MESH] |Case-Control Studies [MESH] |Enzyme-Linked Immunosorbent Assay [MESH] |Humans [MESH] |Immunity, Humoral [MESH] |Immunohistochemistry [MESH] |Immunoprecipitation [MESH] |Inflammation [MESH] |Kidney/*immunology/pathology [MESH] |Lupus Nephritis/*immunology/pathology [MESH] |Mass Spectrometry [MESH] |Microscopy, Confocal [MESH] |Nephritis, Interstitial/*immunology/pathology [MESH] |Severity of Illness Index [MESH] |Vimentin/*immunology [MESH]Vimentin is a dominant target of in situ humoral immunity in human lup(epmc).pdf DeepDyve Pubget Overpricing