Background/Purpose: Anti- Cytolethal Distending Toxin (CDT) antibodies may serve as biomarkers for post-infectious autoimmunity and aid in clinical risk stratification. In this study, we aimed to determine the prevalence of anti-CDT antibodies in a large, well-characterized cohort of patients with systemic sclerosis (SSc) and to examine associations with gastrointestinal (GI) and extraintestinal clinical features and other SSc-related antibodies.

Methods: Sera from 130 well-characterized patients with SSc 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.

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 (worse) among anti-CDT -positive patients [1 (1, 2) vs. 0 (0, 2); p=0.037]. In multivariable analyses, anti-CDT antibodies remained significantly associated with anti-U11/U12 (RNPC3) [OR 19.0 (4.3, 83.4); p= < 0.001), anti-U1RNP antibodies [OR 7.2 (1.9, 27.9); p=0.004] and anti-topoisomerase-1 antibodies [OR 4.7 (1.3, 16.8); p=0.019], even after adjusting for potential confounders.

Conclusion: Anti-CDT antibodies may serve as markers of post-infectious autoimmunity and are strongly associated with SSc-specific autoantibodies linked to severe, progressive GI disease. Understanding the connection between anti-CDT antibodies and autoimmune mechanisms may provide insight into disease pathogenesis.

Table 1. Comparison of demographic, clinical and serological features between anti-CDT antibody positive and negative patients with systemic sclerosis.

SD= standard deviation; IQR = interquartile range; FVC = forced vital capacity; DLco =diffusing capacity for carbon monoxide; RVSP = right ventricular systolic pressure; p= p-value.

§ Disease duration from any first symptom to the date of the serum sample collection.

‡ Maximum Medsger severity score ever recorded in the database; FVC and DLco are represented by the minimum values ever recorded.

*UCLA GIT 2.0, University of California Los Angeles Scleroderma Clinical Trials Consortium gastrointestinal tract 2.0.

† Statistically significant.

Table 2. Statistical models assessing the association between anti–CDT–positive patients with systemic sclerosis and clinical, serological features.

† Statistically significant.

*Values are odds ratio (95% confidence interval).

« Back to ACR Convergence 2025

ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-cytolethal-distending-toxin-antibodies-in-systemic-sclerosis-associations-with-gastrointestinal-disease-and-immune-dysregulation/