AI Article Synopsis

  • The study aimed to identify new autoantibodies related to systemic sclerosis (SSc) using an innovative protein immunoprecipitation (IP) assay, which helps in diagnosing and predicting the prognosis of SSc patients.
  • Researchers collected serum samples and clinical data from 307 SSc patients and tested them for various autoantibodies, including a non-radioactive protein IP assay for those negative for known autoantibodies.
  • A novel autoantibody targeting nuclear valosin-containing protein-like (NVL) was discovered, which was associated with a higher prevalence of calcinosis and certain types of cancer among affected patients, identifying a distinctive clinical phenotype.

Article 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.

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.

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).

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.

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Source
http://dx.doi.org/10.1093/rheumatology/kead520DOI Listing

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