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Anti-nuclear valosin-containing protein-like autoantibody is associated with calcinosis and higher risk of cancer in systemic sclerosis.

Authors :
Perurena-Prieto J
Viñas-Giménez L
Sanz-Martínez MT
Selva-O'Callaghan A
Callejas-Moraga EL
Colobran R
Guillén-Del-Castillo A
Simeón-Aznar CP
Source :
Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2024 Aug 01; Vol. 63 (8), pp. 2278-2283.
Publication Year :
2024

Abstract

Objectives: Systemic sclerosis (SSc)-specific autoantibodies allow the diagnosis and predict the prognosis of SSc patients with different clinical characteristics. The aim of this study was to describe new SSc-related autoantibodies by a novel protein immunoprecipitation (IP) assay.<br />Methods: Serum samples and clinical data were collected from 307 SSc patients. Antinuclear autoantibodies were tested in all patients by indirect immunofluorescence (IIF) on HEp-2 cells. SSc-specific autoantibodies were evaluated with a commercial immunoblot and chemiluminescence immunoassay, and traditional RNA-IP. Patients negative for all these autoantibodies (n = 51) were further tested with a non-radioactive protein IP assay. Protein bands detected on SDS-PAGE were then analysed by mass spectrometry (MS) and confirmed by western blot (WB). Additional 56 patients with nucleolar pattern by IIF were tested by protein IP-WB.<br />Results: Five patients who underwent protein IP testing showed a 110-115kDa molecular weight band on SDS-PAGE and a homogeneous nucleolar pattern by IIF. MS identified the bands as nuclear valosin-containing protein-like (NVL). An additional positive patient was detected by IP-WB. As compared with the remaining 101 negative patients, anti-NVL positive patients showed a greater prevalence of calcinosis (100% vs 18.9%, P < 0.001), and cancer (66.7% vs 8.9%, P = 0.002), with a particular association with synchronous cancer (OR = 16.3; P = 0.024).<br />Conclusion: We identified NVL as a new autoantibody target by a novel protein IP assay in SSc patients with a homogeneous nucleolar IIF pattern, testing negative for all known SSc-specific autoantibodies by commercial assays and RNA IP. Anti-NVL identifies a new clinical phenotype, characterized by calcinosis and cancer.<br /> (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Details

Language :
English
ISSN :
1462-0332
Volume :
63
Issue :
8
Database :
MEDLINE
Journal :
Rheumatology (Oxford, England)
Publication Type :
Academic Journal
Accession number :
37769243
Full Text :
https://doi.org/10.1093/rheumatology/kead520