PD‐1/PD‐L1 expression in pediatric duodenal biopsies: Association with mucosal activity and diagnostic performance in celiac disease

OBJECTIVES: The role of immune checkpoint molecules (ICMs) in celiac disease (CD) remains incompletely understood despite their expected function in limiting mucosal immune-mediated injury. This study aimed to evaluate duodenal PD-1 and PD-L1 expression in pediatric duodenal samples, investigate associations with histologic/serologic activity, and assess their diagnostic performance. METHODS: Patients' files who applied to the pediatric gastroenterology clinic and underwent esophagogastroduodenoscopy between 01.01.2022 and 31.12.2023 were retrospectively reviewed. CD was defined by European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN)-based clinicopathologic correlation. PD-1/PD-L1 immunohistochemistry was quantified as the number of positive mononuclear cells per HPF (40x) in the lamina propria in hot spot areas. The diagnostic potential in differentiating CD and non-CD cases was investigated with receiver operating characteristics (ROC) analysis. RESULTS: A total of 142 children (mean age 10.3 ± 4.4 years; 64.8% male); 68 (47.9%) had CD, and 74 (52.1%) served as non-CD controls. Both markers were significantly elevated in CD tissues (p < 0.001). In ROC analysis, PD-L1 outperformed PD-1 for identifying CD (area under the curve: 0.933 vs. 0.809). A PD-L1 > 6.5/HPF cut-off yielded 92.6% sensitivity and 83.8% specificity. PD-L1 was associated with an increase in Marsh grade in CD samples (p = 0.033) and with an increase in IEL in non-CD cases (p = 0.016). CONCLUSION: PD-1 and PD-L1 are specifically increased in CD, and PD-L1 could be a candidate diagnostic marker for CD. In autoimmune disorders such as CD, elucidating the interactions, functional capacities, and degrees of involvement of these molecules can provide insights into the pathogenesis, diagnosis, and treatment.