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BRIEF RESEARCH REPORT article

Front. Med.
Sec. Rheumatology
Volume 11 - 2024 | doi: 10.3389/fmed.2024.1477365
This article is part of the Research Topic Community Series in Autoantibodies: Volume II View all 9 articles

Identification of nuclear valosin-containing-protein-like as a target of anti-nuclear autoantibodies in systemic sclerosis

Provisionally accepted
Zitao Zeng Zitao Zeng 1*Ramona Miske Ramona Miske 1Madeleine Scharf Madeleine Scharf 1Yvonne Denno Yvonne Denno 1Anthonina Ott Anthonina Ott 1Stefanie Brakopp Stefanie Brakopp 1Bianca Teegen Bianca Teegen 2Winfried Stöcker Winfried Stöcker 2Elise Siegert Elise Siegert 3,4Sandra Saschenbrecker Sandra Saschenbrecker 1Christian Probst Christian Probst 1Lars Komorowski Lars Komorowski 1
  • 1 Institute for Experimental Immunology, affiliated to EUROIMMUN Medizinische Labordiagnostika AG, Lübeck, Germany
  • 2 Clinical Immunological Laboratory Prof. Dr. med. Winfried Stöcker, Groß Grönau, Germany
  • 3 Department of Rheumatology and Clinical Immunology, Charité – Universitätsmedizin Berlin, Berlin, Germany
  • 4 Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany

The final, formatted version of the article will be published soon.

    Objective: To identify the target antigen of an anti-nuclear autoantibody (ANA) from a patient with a suspected systemic autoimmune disease and to study the autoantibody’s clinical association. Methods: The index patient serum was screened for autoantibodies using indirect immunofluorescence assay (IFA) and line blots (membrane strips coated with parallel lines of different purified antigens). Immunoprecipitation with fixed HEp-2 cells followed by SDS-PAGE and MALDI-TOF mass spectrometry was used to identify the autoantigen, which was verified by competitive inhibition experiments, recombinant HEK293 cell-based IFA, and Western and line blots based on the recombinant antigen. The prevalence of autoantibodies against this antigen was studied in 693 patients with systemic autoimmune rheumatic diseases (SARD) and 150 healthy controls. Results: The index patient serum displayed a homogeneous nucleolar staining pattern on HEp-2 cells and monkey liver by IFA but did not react with 27 known nuclear antigens. Nuclear valosin-containing-protein-like (NVL) was identified as the ANA target antigen. Preincubation with recombinant NVL abolished the reactivity of the patient serum with HEp-2 cells in IFA. Additionally, the patient serum reacted with recombinant NVL in cell-based IFA and Western blot analysis, whereas sera from 15 healthy controls were nonreactive. Using line blots coated with recombinant NVL, anti-NVL autoantibodies were exclusively found in four out of 378 patients with systemic sclerosis, but neither in 315 patients with other SARD nor in 150 healthy controls. Conclusion: These findings indicate that autoantibodies against NVL may be a suitable marker to help narrowing the serological gap in systemic sclerosis.

    Keywords: Autoantibodies, autoimmune disease, biomarker, diagnosis, nuclear valosincontaining-protein-like, NVL, systemic sclerosis

    Received: 07 Aug 2024; Accepted: 19 Dec 2024.

    Copyright: © 2024 Zeng, Miske, Scharf, Denno, Ott, Brakopp, Teegen, Stöcker, Siegert, Saschenbrecker, Probst and Komorowski. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Zitao Zeng, Institute for Experimental Immunology, affiliated to EUROIMMUN Medizinische Labordiagnostika AG, Lübeck, Germany

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