Evaluation of antimicrobial antibodies in patients with intestinal pathologies

Abstract

Introduction: Inflammatory bowel disease (IBD) is a chronic immune-mediated condition characterized by dysregulated mucosal immune responses to intestinal antigens. Immunoglobulin A (IgA) and immunoglobulin G (IgG) play complementary roles in mucosal and systemic immunity, yet most studies examining IgA- and IgG-mediated responses to the gut microbiota—including analyses of antibody-coated fecal bacteria—have been conducted in North America, Europe, or East Asia. Immunologic data from South America remain limited. Objective: The aim of this study was to characterize systemic and intestinal humoral immune responses in a Uruguayan cohort by evaluating total antibodies in plasma, and fecal soluble and bacteria-associated IgA and IgG across patients with IBD, irritable bowel syndrome (IBS), celiac disease, and healthy controls. Methodology: Plasma IgA and IgG concentrations were quantified using direct enzyme-linked immunosorbent assays (ELISA). Soluble fecal IgA and IgG were measured by direct ELISA in available stool samples. Flow cytometry was employed to assess IgA- and IgG-associated bacterial signal, expressed as background-normalized fluorescence ratios. Within the IBD group, immunoglobulin (Ig) measures were additionally analyzed according to self-reported symptom presence status and C-reactive protein (CRP) levels. Results: Plasma IgA and IgG concentrations did not differ significantly across diagnostic groups. Soluble fecal IgA and IgG similarly had no statistically significant differences observed at the group level. Flow cytometric measures of IgA- and IgG-associated bacterial signal showed no significant differences between diagnostic groups. Additionally, fecal Ig concentrations and Ig-associated bacterial signals did not differ significantly between symptomatic and asymptomatic subgroups within IBD. An exploratory multivariable Spearman correlation analysis revealed coordinated patterns within compartments: plasma IgA and IgG concentrations were positively correlated, as were fecal IgA and fecal IgG concentrations. IgA- and IgG-associated bacterial measures were also positively correlated, and both soluble fecal IgA and IgG levels demonstrated modest but significant positive associations with IgG-coated bacterial fluorescence. No significant correlations were observed between plasma Ig concentrations and mucosal or bacteria-associated antibody measures. When CRP was analyzed as a categorical variable (elevated vs non-elevated), no statistically significant differences were observed in soluble fecal IgA, soluble fecal IgG, or in the proportion of IgG-coated bacteria within the IBD group. A statistically significant difference was identified in the proportion of IgA-coated bacteria, with higher values observed among IBD participants with non-elevated CRP; however, this finding was based on a small subgroup comparison (n = 8, n = 3) and should be interpreted cautiously. Conclusion: In this Uruguayan cohort, systemic and intestinal Ig measures were characterized by substantial heterogeneity rather than clear diagnostic group separation, with no consistent differences in total plasma or fecal antibody levels or bacterial coating patterns between patient groups and healthy controls. However, multivariable analyses revealed coordinated IgA–IgG patterns within systemic and mucosal compartments and modest associations between fecal Ig levels and IgG-coated bacteria, indicating structured humoral organization despite limited group-level discrimination. These findings suggest that IgA- and IgG-based immune signatures may reflect compartment-specific and individual-level mucosal immune dynamics rather than disease classification alone. Perspectives: This study provides population-specific immunologic data from South America and highlights the need for larger stool-based cohorts and stratified analyses to determine whether IgA- and IgG-based intestinal immune profiling can reliably detect and distinguish between inflammatory and non-inflammatory gastrointestinal disorders in this setting.