Emerging markers in celiac disease.

Abstract

Celiac disease (CD) is a chronic autoimmune disorder triggered by gluten ingestion in genetically predisposed individuals. Current diagnostic methods rely on serological markers, histological examination of duodenal biopsies, and HLA genotyping. However, these approaches have limitations. Advancements in serology have introduced novel autoantibodies beyond tissue transglutaminase (tTG) and endomysial antibodies (EMA), such as neo-epitope tTG and transglutaminase isoforms. Genetic and epigenetic markers, including non-HLA risk alleles, DNA methylation patterns, and non-coding RNAs, provide deeper insights into CD susceptibility. Additionally, cytokine profiling and immune response markers, such as pro-inflammatory and anti-inflammatory cytokines, chemokines, and adhesion molecules, reflect disease pathophysiology and may serve as diagnostic and prognostic tools. Gut microbiota alterations and metabolomic signatures further highlight immune dysregulation and metabolic changes in CD, offering potential biomarkers for diagnosis and disease monitoring. Protein and peptide biomarkers, including intestinal fatty acid-binding protein (I-FABP), plasma citrulline, and regenerating gene Ia (REG Ia), provide insights into intestinal damage and mucosal healing. Furthermore, emerging technologies such as point-of-care testing (POCT) and nanoparticle-based assays enhance diagnostic precision. The objective of this chapter is to provide a comprehensive review of emerging biomarkers and novel technologies that can improve the diagnosis and monitoring of CD. Emphasis is placed on advances in serology, genetic and epigenetic profiling, immune and cytokine markers, metabolomics, and gut microbiota analysis. The chapter also discusses the integration of multi-omics approaches and artificial intelligence-driven analysis as future directions for refining diagnostic accuracy and enabling personalized disease management.