Anti-Vinculin Antibodies in Systemic Sclerosis (SSc): A Potential Biomarker Linking Vascular and Gastrointestinal System Involvement in Two Phenotypically Distinctive SSc Groups

Yossra A Suliman¹, Suzanne Kafaja², Gianluca Bagnato³, Mohamed Alemam⁴, Isela Valera⁵, Walter Morales⁶, Mark Pimentel⁷, Francesco Del Galdo⁸ and Daniel E. Furst⁹, ¹Rheumatology and Rehabilitation dept., Rheumatology and Rehabilitation dept. Assiut university hospital, Assiut Egypt, Assiut, Egypt, ²Department of Internal Medicine, University of California Los Angeles, David Geffen School of Medicine, Division of Rheumatology, Los Angeles, CA, ³Leeds Musculoskeletal Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom, ⁴Clinical Pathology and Laboratory Medicine Department, Lecturer, Qena, Egypt, ⁵Autoimmunity and Tolerance Laboratory, Division of Rheumatology, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, ⁶GI Motility Program, Research associate, Los Angeles, CA, ⁷Gastrointestinal, Cedar Sinai Medical Center, Los Angeles, CA, ⁸Leeds Biomedical Research Centre and Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom, ⁹Medicine, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Biomarkers, Gastrointestinal complications and scleroderma

Session Information

Date: Wednesday, October 24, 2018

Title: 6W012 ACR Abstract: Systemic Sclerosis & Rel D/O III:Cohort Study, Biomarkers, & Response(2934–2939)

Session Type: ACR Concurrent Abstract Session

Session Time: 9:00AM-10:30AM

Background/Purpose:

Vinculin is a cytoskeletal protein that plays a major role in cell-cell and cell-extracellular matrix adhesion thus regulating cell growth, migration and function of enteric nerves, smooth muscles as well as endothelial cells. Antibodies directed against vinculin protein have been identified as biomarker in irritable bowel syndrome (IBS). Recently, vinculin was identified as one of the targets of anti-endothelial antibodies in serum of SSc patients.

Aim: To evaluate serum anti-vinculin antibodies (aVin-abs) in two phenotypically different SSc patient cohorts (vascular and gastrointestinal-enriched groups).

Methods: Controls and SSc subjects recruited from two SSc centers (University of California, Los Angeles [UCLA], USA and the University of Leeds, UK. Subjects were assessed as two groups:

Group I (gastrointestinal [GI] enriched group) included 83 SSc patients (pts), where 55 pts were noted to have a gastrointestinal (GI) Visual analogue scale [GI-VAS] > 40/ 100 whereby GI-VAS was a component of SSc Health Assessment Questionnaire. Group II (vascular-enriched group) included 72 SSc pts, of whom n=17 had digital ulcers, and n=23 had known pulmonary artery hypertension. SSc serum samples as well as 50 age and sex matched controls were evaluated in one laboratory, where aVin-abs were tested by ELISA and results reported as OD. Clinical data were obtained by chart review for statistical correlations.

Results:

Features and demographics of recruited SSc subjects supported the group assignments (Table 1). Among all SSC patients, aVin-abs were significantly higher in SSc groups than in controls (1.4±0.9 compared to 0.6±0.6 in control [p-value=0.002] in Group I) and, (1.0±1.0 in SSc versus 0.6±0.6 in control [p-value =0.01] in Group II).

Group I (GI-enriched) patients were then dichotomized based on aVin-abs cutoff level (used in IBS study [high>1.7 or low< 1.7]). Using this cutoff, BMI was significantly lower in SSc pts with high levels of abs (19.9±4.1kg/m²) versus low levels (21.9±4.7) (p=0.05). Significantly higher GI-VAS was recorded in SSc pts with high aVin-abs (6 [range 2-9]) in comparison to SSc pts with low (2 [range1-9]) (p-value=0.0001). In group II, we examined predictors of higher aVin-abs in group II (vascular -enriched): BMI and PAH were significant predictors of higher anti-vinculin (p<0.005 and 0.04, respectively

Conclusion: This is one of the first studies to report an association between autoimmunity to vinculin in patients with SSc-GI involvement. This suggests that higher aVin-abs are associated with greater severity of GI involvement with consequent decreased BMI. In addition, we report that aVin-abs also appear associated with vasculopathy such as pulmonary artery hypertension.

	Group I	Group II
Age mean (SD)	57.4 (12.64)	56.36 (13.83)
Sex: females	69 (83%)	58(82.85%)
Diffuse subtype	24 (29%)	(32) 48.48%
BMI Mean (SD)	26.16 (5.71)	24.3 (4.25)
GI-VAS	3 (1-9)	2.2 (0-9)
PAH	5(6%)	23 (31%)
Current skin ulcers	30(36%),	17 (25%)
FVC mean (± SD)	98.3 ± 25.2	79.8 ± 26.1

Disclosure: Y. A. Suliman, None; S. Kafaja, None; G. Bagnato, None; M. Alemam, None; I. Valera, None; W. Morales, None; M. Pimentel, None; F. Del Galdo, None; D. E. Furst, None.

To cite this abstract in AMA style:

Suliman YA, Kafaja S, Bagnato G, Alemam M, Valera I, Morales W, Pimentel M, Del Galdo F, Furst DE. Anti-Vinculin Antibodies in Systemic Sclerosis (SSc): A Potential Biomarker Linking Vascular and Gastrointestinal System Involvement in Two Phenotypically Distinctive SSc Groups [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/anti-vinculin-antibodies-in-systemic-sclerosis-ssc-a-potential-biomarker-linking-vascular-and-gastrointestinal-system-involvement-in-two-phenotypically-distinctive-ssc-groups/. Accessed .

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