Anti-vinculin antibodies in scleroderma (SSc): a potential link between autoimmunity and gastrointestinal system involvement in two SSc cohorts

Abstract

Background

Systemic sclerosis (SSc) is an autoimmune disorder and commonly presents with vascular system involvement and motility disorders in the gastrointestinal (GI) tract. Vinculin is a cytoskeletal protein that plays major roles in cell-cell adhesion and is expressed in the neuromuscular apparatus of the gut. Antibodies to vinculin have been identified as a biomarker of irritable bowel syndrome (IBS). Our aim was to evaluate serum anti-vinculin antibodies in patients with SSc.

Methods

Patients were recruited from two SSc centers: group I (GI-enriched group), University of Leeds, UK, and Group II (vascular predominant), University of California, Los Angeles. Serum samples of patients recruited from two SSc centres, Group I ( GI enriched group), University of Leeds, UK and Group II (Vascular predominant), University of California, Los Angeles) were collected. Samples from age- and sex-matched healthy volunteers (N = 88) were used as controls.

Results

Group I (GI-enriched group, N = 83) patients were 58 [50–67] years old; 83% were females with a median body mass index (BMI) of 20.3 (21.2 ± 4.5) [18–23]. Group II (vascular-enriched group, N = 72) patients were 58 [50–67] years old; 80% were female, and BMI was 23.9 (21.3–26.9). More subjects in group I had prominent GI involvement (N = 55, 66%) than group II (12, 16%), p ˂ 0.0001. Anti-vinculin antibody levels in SSc group I (1.3 [0.9]) were significantly higher than in HC (0.7 [0.8]; p = 0.002). When pooled, circulating anti-vinculin levels in both SSc groups remained significantly higher than in the HC group (p = 0.02). Higher anti-vinculin levels were associated with higher GI-visual analogue scale (GI-VAS) scores and specifically with GI-VAS scores of ≥ 4 (p < 0.0001).

Conclusion

This study demonstrates that elevated anti-vinculin antibody levels are common in SSc and suggests a potential link between increased anti-vinculin levels and GI tract symptoms.

Key Points:
Anti-vinculin antibodies are elevated in systemic sclerosis and are relatively common.
In these SSc patients, anti-vinculin antibodies are associated with higher levels of GI symptoms in SSc.
A potential link between anti-vinculin antibodies and vascular system involvement was shown.

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Correspondence to Daniel E Furst.

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Disclosures

Yossra Suliman, Suzanne Kafaja, Sunny J OH, G. Bagnato, G. Abignano, X. Liu, M. Alemam, I. Valera, RR. Singh, G. Barlow, F. Del Galdo, and D.E. Furst have no disclosures. Dr. Pimentel is a board member of Gemelli Biotech and has equity in this company (> $10,000). Ali Rezaie has received speaker/consultant fees and research funding from Valeant Pharmaceuticals and has equity in Gemelli Biotech (all > $10,000). Walter Morales is a consultant for Gemelli Biotech (< $10,000).

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This work was accepted as a poster presentation and as an oral presentation by the American College of Rheumatology in 2016 and 2018 respectively (https://acrabstracts.org/?post_type=abstracts&s=vinculin) (2018 ACR/ARHP Annual Meeting(Anti-vinculin Antibodies in Systemic Sclerosis (SSc): A Potential Biomarker Linking Vascular and Gastrointestinal System Involvement in Two Phenotypically Distinctive SSc Groups) and 2016 ACR/ARHP Annual Meeting (Anti-vinculin Antibodies: A Novel Biomarker in Systemic Sclerosis, and Its Association with Vascular Involvement).

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Suliman, Y., Kafaja, S., Oh, S.J. et al. Anti-vinculin antibodies in scleroderma (SSc): a potential link between autoimmunity and gastrointestinal system involvement in two SSc cohorts. Clin Rheumatol (2020). https://doi.org/10.1007/s10067-020-05479-5

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Keywords

  • Anti-vinculin
  • GI tract
  • SSc
  • Vascular