Comparative Role of Heat Shock Protein 70 and tTG Autoantibodies as Biomarkers in Diagnosis and Follow-up of Marsh 3 Celiac Disease

Abstract

Background: Celiac disease (CD) is an autoimmune disorder characterized by an abnormal immune response to gluten, leading to intestinal mucosal damage. Anti-tissue transglutaminase (anti-tTG) antibodies are well-known ways to diagnose CD. However, it is still not clear what role heat shock protein 70 (HSP70) plays in the disease and protecting the mucosa. Objective: To evaluate serum and tissue levels of anti-tTG antibodies and HSP70 in patients with celiac disease and assess their potential as biomarkers for disease diagnosis and progression. Methods: This case-control study included 64 CD patients and 26 healthy controls from Al-Anbar province. Anti-tTG IgA and IgG serum levels were analyzed, and HSP70 tissue expression was assessed in samples from a duodenal biopsy. Histopathological findings were graded according to the Marsh classification. Results: CD was more prevalent in females (56.5%) than males (37.5%). Serum anti-tTG IgA and IgG levels were significantly elevated in CD patients compared to controls and correlated with the degree of intestinal damage. Both antibodies showed a progressive increase from Marsh 3A to 3C, with Marsh 3C exhibiting the highest levels (tTG-IgA: 19.12 µg/mL; tTG-IgG: 13.44 µg/mL). In contrast, HSP70 tissue expression was low or absent in 53.2% of CD patients, particularly in those with severe mucosal injury (Marsh 3C). Conclusions: Anti-tTG antibodies remain useful for confirming CD diagnosis but are limited in predicting disease progression. HSP70 expression, which declines with increasing mucosal damage, may serve as a complementary biomarker reflecting cellular stress, mucosal integrity, and early disease activity.