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NVL Identified as ANA Target to Narrow Serological Gap in Systemic Sclerosis

By LabMedica International staff writers
Posted on 03 Jun 2025

Anti-nuclear autoantibodies (ANA) are important biomarkers of systemic autoimmune rheumatic diseases (SARD) and play a crucial role in disease identification and clinical decision-making. More...

They are detected using the indirect immunofluorescence assay (IFA) on HEp-2 cells as the gold standard, followed by monospecific confirmatory assays. However, there is a subset of SARD patients with unknown ANA reactivity. For example, about 20% of systemic sclerosis (SSc) patients with a positive nuclear pattern in IFA have autoantibodies against an unknown target antigen. In a new study published in Frontiers in Medicine, researchers have identified nuclear valosin-containing-protein-like (NVL) as the target antigen of ANA in a patient with suspected systemic autoimmune disease.

In the collaborative study undertaken by EUROIMMUN (Lübeck, Germany) and Charité - Universitätsmedizin Berlin (Berlin, Germany), researchers found that the serum of the index patient displayed a homogeneous nucleolar staining pattern on HEp-2 cells and monkey liver (EUROIMMUN IFA BIOCHIP Mosaic), but negative results with 27 ANA target antigens on confirmatory immunoblots (EUROLINE). NVL was identified as the target antigen by immunoprecipitation and mass spectrometry. Results were confirmed using competitive inhibition experiments, cell-based assay (CBA) and immunoblots based on recombinant antigen. The prevalence of anti-NVL autoantibodies was subsequently investigated in 693 patients with SARD and 150 healthy controls using line blot. Anti-NVL autoantibodies were detected in four out of 378 patients with SSc, representing 1.1% of this cohort, but not in 315 patients with other SARD or in healthy controls.

Two of the four anti-NVL-positive patients additionally exhibited other SSc-relevant autoantibodies, namely anti-centromere and anti-PM-Scl100 autoantibodies. The researchers concluded that anti-NVL autoantibodies may be a suitable marker to help narrow the serological gap in SSc. NVL belongs to ATPases associated with various cellular activities. It shows a high level of amino acid similarity to valosin-containing protein (VCP), which has also been described as a target antigen in autoimmune diseases. Further studies will help to determine if anti-NVL reactivity correlates with a specific SSc phenotype or therapy response. The NVL antigen is now included in the EUROLINE Systemic Sclerosis Profile 2 (EUROIMMUN), together with 12 established antigens associated with SSc and overlap syndromes. This assay is the only commercially available line blot containing NVL. The line blot offers the advantage of multiplex analysis of a broad spectrum of relevant autoantibodies in parallel.

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