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

IF 5.2 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Liver International Pub Date : 2025-09-13 DOI:10.1111/liv.70350

Boglarka Balogh, David Tornai, Aniko Csillag, Istvan Tornai, Zsuzsana Vitalis, Patricia Kovats, Peter Antal-Szalmas, Tamas Dinya, Wim Laleman, Minneke J. Coenraad, Jonel Trebicka, Maria Papp, MICROB-PREDICT and PREDICT study group of the EASL-CLIF consortium

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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.

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分泌IgA是预测ACLF预后的关键指标之一

背景和目的在肝硬化中，受损的肠道黏膜免疫促进了细菌易位（BT），引发了促炎级联反应，加剧了肝损伤。抗体介导的免疫在这一过程中的作用尚不清楚。我们评估了与肠道屏障功能相关的血清免疫球蛋白（Ig）在急性失代偿（AD）肝硬化患者的前瞻性MICROB-PREDICT队列中的预后标志物。方法检测128例患者血清中不同靶点（丝状肌动蛋白、酿酒酵母（Saccharomyces cerevisiae， ASCA）、糖蛋白-2 （GP2）、麦胶蛋白（gliadin）、内毒素核心（EndoCab））的IgA和IgG抗体、分泌IgA、总IgA、IgG、IgM和游离Ig kappa/lambda轻链。在3个月的随访期间评估死亡率。一个独立的ACLF患者队列（n = 50）被用来验证siga相关发现。结果iga型靶特异性抗体的发生率高于IgG型。靶特异性抗体多样性和浓度、总iga水平和Child-Pugh严重程度呈现一致的升高。总igg水平与CLIF-C AD评分和ACLF的存在呈负相关。sIgA水平随ACLF评分平行升高。sIgA水平升高与ACLF患者90天死亡率相关（n = 37; AUROC: 0.859；截止值为20.9 μg/mL: 11.1% vs. 78.9%死亡率p <； 0.001）。这些发现在验证队列中得到证实。在合并ACLF队列中（n = 87），高sIgA水平预测90天死亡率，与ccliff - c ACLF评分无关（HR: 3.367; CI: 1.563-7.225; p = 0.002）。结论bt触发的免疫激活增强，表明总IgA水平升高与目标特异性IgA抗体的发生有关。血清sIgA是ACLF患者肠道屏障功能衰竭和90天死亡率的一个有希望的指标。

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来源期刊

Liver International 医学-胃肠肝病学

CiteScore

13.90

自引率

4.50%

发文量

348

审稿时长

2 months

期刊介绍： Liver International promotes all aspects of the science of hepatology from basic research to applied clinical studies. Providing an international forum for the publication of high-quality original research in hepatology, it is an essential resource for everyone working on normal and abnormal structure and function in the liver and its constituent cells, including clinicians and basic scientists involved in the multi-disciplinary field of hepatology. The journal welcomes articles from all fields of hepatology, which may be published as original articles, brief definitive reports, reviews, mini-reviews, images in hepatology and letters to the Editor.