Serum thiol redox-related alterations in asymptomatic first-degree relatives are associated with future Crohn's disease.

BACKGROUND

Increased oxidative stress is well documented in patients with Crohn's disease (CD). However, it remains unclear whether early redox-related alterations occur prior to diagnosis and whether they are correlated with early alterations in inflammatory responses.

AIMS: We examined whether the serum cysteine sulfinic acid to cysteine ratio, as a redox-related marker indicative of sustained oxidative conditions, is associated with future CD risk and correlated with gut and systemic inflammation, proteomic, and metabolomic profiles.

METHODS

In the Genetic, Environmental, and Microbial (GEM) Project, 79 healthy first-degree relatives (FDRs) who later developed CD (Pre-CD) were identified and matched by age, sex, geographic location, and time of recruitment with 311 FDRs who remained disease-free. Conditional logistic regression assessed the association between redox biomarkers and future CD risk. Partial Spearman correlation assessed correlations between the cysteine sulfinic acid to cysteine ratio and C-reactive protein (CRP), fecal calprotectin (FCP), serum metabolites (Metabolon®), and serum proteomic profiles (Olink®).

RESULTS

An elevated serum cysteine sulfinic acid to cysteine ratio was positively associated with the risk of developing CD (odds ratio = 2.06, 95% CI: 1.42-3.00, p = 0.00015) and showed a positive correlation with CRP (coefficient = 0.296; p = 3.04e-09) and FCP (coefficient = 0.123; p = 0.0198) levels. A total of 295 metabolites and 201 proteins were correlated with the cysteine sulfinic acid to cysteine ratio.

CONCLUSION

This study provides new evidence that redox-related alterations are present during the preclinical phase prior to CD onset.