Secretory IgA Is a Key Marker Among Gut Barrier Dysfunction-Related Immunoglobulins Predicting Outcomes in ACLF

Background and Aims

In cirrhosis, impaired gut mucosal immunity facilitates bacterial translocation (BT) instigating the proinflammatory cascade that exacerbates hepatic damage. The role of antibody-mediated immunity in this process remains unclear. We assessed serum immunoglobulins (Ig) linked to gut barrier function as prognostic markers in a prospective MICROB-PREDICT cohort of patients with acutely decompensated (AD) cirrhosis.

Methods

Serum samples of 128 patients were assayed for IgA and IgG antibodies against various targets (filamentous-actin; Saccharomyces cerevisiae [ASCA]; glycoprotein-2 [GP2]; gliadin; endotoxin-core [EndoCab]), secretory (s)IgA, total-IgA, IgG, IgM and free Ig kappa/lambda light chains. Mortality was assessed during a 3-month follow-up period. An independent ACLF patient cohort (n = 50) was used to validate sIgA-related findings.

Results

IgA-type target-specific antibodies were more prevalent than IgG types. Target-specific antibody diversity and concentrations, total-IgA levels and Child–Pugh severity exhibited concordant elevations. Total-IgG levels were inversely associated with CLIF-C AD score and presence of ACLF. sIgA levels increased in parallel with ACLF grades. Elevated sIgA levels were associated with 90-day mortality in ACLF patients (n = 37; AUROC: 0.859; at the cut-off of > 20.9 μg/mL: 11.1% vs. 78.9% Mortality p < 0.001). These findings were confirmed in the validation cohort. In the merged ACLF cohort (n = 87), high sIgA levels predicted 90-day mortality independent of CLIF-C ACLF score (HR: 3.367; CI: 1.563–7.225; p = 0.002).

Conclusion

Enhanced BT-triggered immune activation is indicated by increased total-IgA levels in association with the occurrence of target-specific IgA antibodies. Serum sIgA is a promising marker of gut barrier failure and 90-day mortality in ACLF.