Volume 16 Supplement 1

Lupus 2014: New Targets, New Approaches

Open Access

Vimentin is a dominant target of in situ humoral immunity in human lupus tubulointerstitial nephritis

  • Marcus R Clark1Email author,
  • Anthony Chang1,
  • Kichul Ko1,
  • Carole J Henry Dunand1,
  • Scott Henderson1,
  • Dan Brandt1,
  • Natalya Kaverina1,
  • Vladimir Liarski1,
  • Patrick C Wilson1 and
  • Andrew J Kinloch1
Arthritis Research & Therapy201416(Suppl 1):A18

https://doi.org/10.1186/ar4634

Published: 18 September 2014

Background

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 dominant autoantigen(s) driving in situ B-cell selection in TII are not known.

Methods

Single CD38+ or Ki-67+ B cells were laser captured from seven LuN biopsies. Twenty clonally expanded immunoglobulin heavy and light chain variable region pairs were cloned and expressed as 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 45 LuN and 38 non-nephritic lupus samples using purified antigen-coated arrays. Autoantigen expression was localized by immunohistochemistry and immunofluorescence on normal and LuN kidney.

Results

Thirteen of 27 antibodies reacted with cytoplasmic structures, four reacted with nuclei and none with dsDNA, Sm or RNP. Vimentin was the only autoantigen identified by both mass spectrometry and on protoarray. Eleven anticytoplasmic 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).

Conclusions

Vimentin, an antigenic feature of inflammation, is a dominant autoantigen targeted in situ in LuN TII. This adaptive autoimmune response probably feeds forward to worsen TII and renal damage.

Authors’ Affiliations

(1)
University of Chicago

Copyright

© Clark et al.; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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