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Anti‐Gephyrin Antibodies: A Novel Specificity in Patients With Systemic Sclerosis and Lower Bowel Dysfunction.
- Source :
- Arthritis & Rheumatology; Jan2024, Vol. 76 Issue 1, p92-99, 8p
- Publication Year :
- 2024
-
Abstract
- Objective: Autoantibodies are clinically useful in phenotyping patients with systemic sclerosis (SSc). Gastrointestinal (GI) function is regulated by the enteric nervous system (ENS) and commonly impaired in SSc, suggesting that the SSc autoimmune response may target ENS antigens. We sought to identify novel anti‐ENS autoantibodies with an aim to clinically phenotype SSc GI dysfunction. Methods: Serum from a patient with SSc with GI dysfunction but without defined SSc‐associated autoantibodies was used for autoantibody discovery. Immunoprecipitations performed with murine myenteric plexus lysates were on‐bead digested, and autoantigens were identified by mass spectrometry. Prevalence was determined, and clinical features associated with novel autoantibodies were evaluated in a SSc cohort using regression analyses. The expression of gephyrin in human GI tract tissue was examined by immunohistochemistry. Results: We identified gephyrin as a novel SSc autoantigen. Anti‐gephyrin antibodies were present in 9% of patients with SSc (16/188) and absent in healthy controls (0/46). Anti‐gephyrin antibody–positive patients had higher constipation scores (1.00 vs 0.50, P = 0.02) and were more likely to have severe constipation and severe distention/bloating (46% vs 15%, P = 0.005; 54% vs 25%, P = 0.023, respectively). Anti‐gephyrin antibody levels were significantly higher among patients with severe constipation (0.04 vs 0.00; P = 0.001) and severe distention and bloating (0.03 vs 0.004; P = 0.010). Severe constipation was associated with anti‐gephyrin antibodies even in the adjusted model. Importantly, gephyrin was expressed in the ENS, which regulates gut motility. Conclusion: Gephyrin is a novel ENS autoantigen that is expressed in human myenteric ganglia. Anti‐gephyrin autoantibodies are associated with the presence and severity of constipation in patients with SSc. [ABSTRACT FROM AUTHOR]
- Subjects :
- AUTOANTIBODIES
AUTONOMIC nervous system
IN vivo studies
STAINS & staining (Microscopy)
ANALYSIS of variance
CONSTIPATION
IMMUNOHISTOCHEMISTRY
SYSTEMIC scleroderma
GASTROINTESTINAL diseases
PRECIPITIN tests
REGRESSION analysis
MANN Whitney U Test
RADIONUCLIDE imaging
IMMUNOBLOTTING
T-test (Statistics)
MASS spectrometry
ENZYME-linked immunosorbent assay
FLUORESCENT antibody technique
CHI-squared test
DESCRIPTIVE statistics
MEMBRANE proteins
DATA analysis software
ANTIGENS
PHENOTYPES
MICE
ABDOMINAL bloating
Subjects
Details
- Language :
- English
- ISSN :
- 23265191
- Volume :
- 76
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Arthritis & Rheumatology
- Publication Type :
- Academic Journal
- Accession number :
- 174515363
- Full Text :
- https://doi.org/10.1002/art.42667