Background/Objectives: Non-celiac gluten sensitivity (NCGS) is a syndrome characterized by intestinal and extraintestinal symptoms triggered by gluten ingestion. Although anti-gliadin IgG antibody (AGA IgG) has been proposed as a potential biomarker for NCGS, its sensitivity and specificity in real-world clinical settings remain unclear. This study aimed to evaluate the clinical utility of AGA IgG in NCGS and to characterize its clinical features, including psychological distress and physical quality of life (QOL), in patients with clinically suspected NCGS attending a specialized outpatient unit in Japan, where patients reported symptoms related to the ingestion of gluten-containing grains (primarily wheat). Methods: We evaluated plasma AGA IgG levels in 45 patients with suspected NCGS based on clinical presentation and in 83 age- and sex-matched healthy controls. Plasma AGA IgG was measured using ELISA. Clinical symptoms and QOL were assessed using validated scales, including the 36-Item Short Form Health Survey (SF-36), Patient Health Questionnaire (PHQ-9 and PHQ-15), Generalized Anxiety Disorder-7 (GAD-7), and the Japanese version of the Irritable Bowel Syndrome Quality of Life measure (IBS-QOL-J). Results: The AGA IgG positivity rate was significantly higher in the suspected NCGS group (33.3%) than in the control group (13.3%; p < 0.01). Using clinical suspicion as the reference, the sensitivity and specificity of AGA IgG were 33.3% and 86.7%, respectively. Patients with suspected NCGS exhibited significantly lower physical and mental QOL and higher scores for depressive, anxiety, and somatic symptoms compared to controls. No significant clinical differences were found between AGA IgG-positive and IgG-negative individuals within the suspected NCGS group. Conclusions: AGA IgG demonstrated a specificity of 86.7% and a sensitivity of 33.3% for suspected NCGS, indicating its limited utility as a standalone biomarker. These findings suggest that suspected NCGS involves significant somatic and psychological burdens regardless of serological status. Future studies should explore whether a multi-marker panel could improve the identification of “True NCGS” in diverse clinical populations.
Motoyama et al. (Mon,) studied this question.