Yossra Suliman1,2, Suzanne Kafaja1, Sunny J Oh3, Mohamed Alemam4, Gianluca Bagnato5, Giuseppina Abignano5,6, Ram Raj Singh1, Gillian Barlow3, Xiaochen Liu3, Isela Valera1, Walter Morales3, Ali Rezaie3, Mark Pimentel3, Francesco Del Galdo5, Daniel E Furst7,8,9. 1. Division of Rheumatology, Department of Internal Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. 2. Rheumatology and Rehabilitation Department, Assiut University Hospital, Assiut, Egypt. 3. Medically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 4. Clinical Pathology and Laboratory Medicine Department, Qena faculty of Medicine, South Valley University, Qena, Egypt. 5. Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK. 6. San Carlo Hospital, Rheumatology Institute of Lucania (IReL), Potenza, Italy. 7. Division of Rheumatology, Department of Internal Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. dan@furst.us.com. 8. Division of Rheumatology, University of Washington, Seattle, WA, USA. dan@furst.us.com. 9. Department of Experimental and Clinical Medicine, Division of Rheumatology, University of Florence, Florence, Italy. dan@furst.us.com.
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.
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.
Authors: Keith M Sullivan; Ellen A Goldmuntz; Lynette Keyes-Elstein; Peter A McSweeney; Ashley Pinckney; Beverly Welch; Maureen D Mayes; Richard A Nash; Leslie J Crofford; Barry Eggleston; Sharon Castina; Linda M Griffith; Julia S Goldstein; Dennis Wallace; Oana Craciunescu; Dinesh Khanna; Rodney J Folz; Jonathan Goldin; E William St Clair; James R Seibold; Kristine Phillips; Shin Mineishi; Robert W Simms; Karen Ballen; Mark H Wener; George E Georges; Shelly Heimfeld; Chitra Hosing; Stephen Forman; Suzanne Kafaja; Richard M Silver; Leroy Griffing; Jan Storek; Sharon LeClercq; Richard Brasington; Mary E Csuka; Christopher Bredeson; Carolyn Keever-Taylor; Robyn T Domsic; M Bashar Kahaleh; Thomas Medsger; Daniel E Furst Journal: N Engl J Med Date: 2018-01-04 Impact factor: 91.245