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

Liver Int. 2025 Oct;45(10):e70350. doi: 10.1111/liv.70350.

Abstract

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.

Keywords: acute‐on‐chronic liver failure; adaptive immunity; gut barrier failure; immunoglobulin A; secretory IgA; short‐term mortality.

MeSH terms

  • Acute-On-Chronic Liver Failure* / blood
  • Acute-On-Chronic Liver Failure* / immunology
  • Acute-On-Chronic Liver Failure* / mortality
  • Adult
  • Aged
  • Bacterial Translocation / immunology
  • Biomarkers / blood
  • Female
  • Humans
  • Immunity, Mucosal
  • Immunoglobulin A, Secretory* / blood
  • Immunoglobulin G / blood
  • Intestinal Mucosa* / immunology
  • Male
  • Middle Aged
  • Prognosis
  • Prospective Studies

Substances

  • Immunoglobulin A, Secretory
  • Biomarkers
  • Immunoglobulin G