Rheumatology (Oxford, England) · 2025
Anti-cytolethal distending toxin antibodies in systemic sclerosis: associations with gastrointestinal disease and immune dysregulation.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Di Ciommo Francesca Romana, Casciola-Rosen Livia, Ayla Ali Yagiz, Balar Ashish, Shah Ami A, Hughes Michael, Morales Walter, Pimentel Mark, Adler Brittany L, McMahan Zsuzanna H
Аннотация
OBJECTIVES: Anti-cytolethal distending toxin (CDT) antibodies may serve as biomarkers for post-infectious autoimmunity and aid clinical risk stratification. We aimed to determine the prevalence of anti-CDT antibodies in a large, well-characterized cohort of systemic sclerosis (SSc) patients and examine associations with gastrointestinal (GI) and extraintestinal clinical features and SSc-related antibodies.
METHODS: Sera from 130 SSc patients enriched for GI disease were screened for anti-CDT antibodies by ELISA. Clinical features, UCLA GIT 2.0-assessed symptoms and autoantibody profiles were compared between patients with and without anti-CDT antibodies. Linear mixed-effects models evaluated whether anti-CDT titres changed over time and correlated with longitudinal UCLA GIT 2.0 scores.
RESULTS: Anti-CDT antibodies were detected in 18% (23/130) of SSc patients. Patients with anti-CDT antibodies more frequently had significant GI disease (87% vs 71%; P = 0.19) and were significantly more likely to have antibodies to U11/U12 (RNPC3) (35% vs 4%; P < 0.001), U1RNP (26% vs 8%; P = 0.018) and topoisomerase-1 (30% vs 12%; P = 0.044). UCLA GIT Soilage scores were significantly higher among anti-CDT positive patients [median (interquartile range) 1 (1-2) vs 0 (0-2); P = 0.037]. In multivariable analyses, anti-CDT antibodies remained significantly associated with anti-U11/U12 (RNPC3) [odds ratio (OR) 19.0 (95% CI: 4.3, 83.4); P ≤ 0.001], anti-U1RNP antibodies [OR 7.2 (95% CI: 1.9, 27.9); P = 0.004] and anti-topoisomerase-1 antibodies [OR 4.7 (95% CI: 1.3, 16.8); P = 0.019], even after adjusting for confounders. Anti-CDT titres did not change significantly over time.
CONCLUSIONS: Anti-CDT antibodies may serve as markers of post-infectious autoimmunity and strongly associate with SSc-autoantibodies linked to severe, progressive GI disease. Understanding the connection between anti-CDT antibodies and SSc-specific autoimmunity may provide insight into disease pathogenesis.
METHODS: Sera from 130 SSc patients enriched for GI disease were screened for anti-CDT antibodies by ELISA. Clinical features, UCLA GIT 2.0-assessed symptoms and autoantibody profiles were compared between patients with and without anti-CDT antibodies. Linear mixed-effects models evaluated whether anti-CDT titres changed over time and correlated with longitudinal UCLA GIT 2.0 scores.
RESULTS: Anti-CDT antibodies were detected in 18% (23/130) of SSc patients. Patients with anti-CDT antibodies more frequently had significant GI disease (87% vs 71%; P = 0.19) and were significantly more likely to have antibodies to U11/U12 (RNPC3) (35% vs 4%; P < 0.001), U1RNP (26% vs 8%; P = 0.018) and topoisomerase-1 (30% vs 12%; P = 0.044). UCLA GIT Soilage scores were significantly higher among anti-CDT positive patients [median (interquartile range) 1 (1-2) vs 0 (0-2); P = 0.037]. In multivariable analyses, anti-CDT antibodies remained significantly associated with anti-U11/U12 (RNPC3) [odds ratio (OR) 19.0 (95% CI: 4.3, 83.4); P ≤ 0.001], anti-U1RNP antibodies [OR 7.2 (95% CI: 1.9, 27.9); P = 0.004] and anti-topoisomerase-1 antibodies [OR 4.7 (95% CI: 1.3, 16.8); P = 0.019], even after adjusting for confounders. Anti-CDT titres did not change significantly over time.
CONCLUSIONS: Anti-CDT antibodies may serve as markers of post-infectious autoimmunity and strongly associate with SSc-autoantibodies linked to severe, progressive GI disease. Understanding the connection between anti-CDT antibodies and SSc-specific autoimmunity may provide insight into disease pathogenesis.