Correlation of Serological Markers, Complement Activation, and Histological Severity in Celiac Disease: Insights from a Cohort Study in Babylon, Iraq

Abstract

Celiac disease (CD) is an autoimmune enteropathy triggered by gluten ingestion, characterized by varying degrees of villous atrophy and immune-mediated mucosal injury. This study aimed to investigate the demographic distribution, serological markers, immune activation, and histological progression of CD in 90 patients recruited from Marjan Teaching Hospital, Babylon Governorate, Iraq, between August 2023 and January 2024. The cohort included 62 females (68.9%) and 28 males (31.1%), stratified into three age groups: 3–15 years (n = 25), 16–30 years (n = 35), and >30 years (n = 30). Serological analysis demonstrated a progressive increase in anti-tissue transglutaminase (anti-tTG) antibodies with advancing Marsh stage, with IgA levels rising from 8.20 ± 2.8 ng/L in Marsh 0 to 59.00 ± 9.1 ng/L in Marsh 3, and IgG levels from 12.46 ± 3.2 ng/L to 60.51 ± 8.5 ng/L. Complement activation, assessed by C5b-9, increased from 95.4 ± 20.1 ng/mL in Marsh 0 to 430.5 ± 55.2 ng/mL in Marsh 3, while IL-17 and IL-21 levels rose from 18.2 ± 5.1 pg/mL and 52.3 ± 12.5 pg/mL to 77.2 ± 12.8 pg/mL and 217.6 ± 35.4 pg/mL, respectively. Histological evaluation confirmed staged mucosal injury, progressing from normal villous architecture and intraepithelial lymphocytes (IELs) <20/100 in Marsh 0 to partial, subtotal, and total villous atrophy (Marsh 3a–3c) with IELs >30/100 in advanced disease. Age-wise distribution revealed milder disease in younger patients and more severe mucosal damage in adults over 30 years, while females were disproportionately affected. These findings indicate that anti-tTG IgA is a reliable diagnostic and monitoring marker, with complement activation and Th17/Th21 cytokines contributing to severe mucosal injury. Early detection and comprehensive serological and histological assessment are essential for effective disease management and may inform therapeutic strategies targeting immune pathways in celiac disease.