Advancing celiac disease research: biomarkers, therapeutics, and patient-centered outcomes

Celiac disease (CD) is a complex, multifactorial autoimmune disorder triggered by gluten ingestion in genetically predisposed individuals. Current serology-based diagnosis relies on tissue transglutaminase (tTG) antibodies —specifically tTG-IgA and tTG-IgG— combined with gliadin-reactive antibodies (deamidated gliadin peptide IgA and IgG) and immunofluorescence detection of endomysial antibodies (EMA), followed by duodenal biopsy confirmation. Despite their clinical utility, these markers have limitations: variable sensitivity and specificity across populations, inability to predict disease progression or mucosal healing kinetics, limited utility in monitoring treatment response, and gaps in detecting patients with seronegative disease or refractory celiac disease (RCD). Meanwhile, many patients experience delayed diagnosis, persistent symptoms despite strict gluten-free diet adherence (non-responsive celiac disease), or long-term complications including malnutrition, bone disease, and increased malignancy risk.This Research Topic brings together international expertise in celiac disease immunology, diagnostics, and patient outcomes to advance the field through three integrated pillars: refinement and expansion of biomarker strategies beyond conventional serology; development and evaluation of emerging therapeutic strategies; and integration of patient-centered outcome measures into research and clinical practice.We invite original research, clinical trials, systematic reviews, and methodological advances addressing celiac disease across the following themes: Biomarkers & Diagnostics - Optimization and standardization of tTG-IgA and tTG-IgG detection across platforms and populations- Deamidated gliadin peptide (DGP) IgA and IgG assays: sensitivity, specificity, and diagnostic algorithms- Endomysial antibody (EMA) immunofluorescence: refinement, automation, and predictive value- Novel serological markers: anti-transglutaminase-2-6 (aTG6), peroxiredoxin-2, lipopolysaccharide-binding protein- Gluten peptide-specific T-cell and B-cell responses; biomarkers of gluten immunogenicity- Proteomic and metabolomic signatures of active CD, treatment response, and mucosal healing- LC-MS and mass spectrometry-based quantification of biomarkers and gluten peptides- Molecular/genetic markers predicting disease progression and immune system complications (e.g., microRNA, epigenetic signatures)- Imaging biomarkers (ultrasound, endoscopy-guided assessment) linked to immunological markers- Biomarkers predicting and tracking mucosal healing in duodenal biopsies and immune-mucosal interactions. Mechanisms & Immunology - Innate and adaptive immune mechanisms; gluten-specific T-cell and B-cell responses- Role of transglutaminase-2 autoimmunity and its pathogenic consequences- Commensal microbiota and environmental factors influencing disease development- Molecular mimicry, cross-reactivity, and epitope spreading- Mechanisms underlying seronegative disease and refractory celiac disease Therapeutics - Enzyme therapies targeting gluten immunogenicity- Immunomodulatory approaches (tolerizing vaccines, regulatory T-cell therapies)- Tight junction modulators and intestinal barrier therapeutics- Anti-TNF and other cytokine-targeted approaches in RCD- Gene and cellular therapy strategies- Microbiota-based interventions Patient-Centered Outcomes - Morphometric and histological assessment of mucosal healing (Marsh staging, Biopsy spacing scale) linked to immunological features.- Nutritional status, bone health, and metabolic outcomes in CD populations and its effects on systemic immunity- Immune system role on long-term complications surveillance (malignancy, osteoporosis, neurological sequelae) or autoimmune comorbidities In Scope for Frontiers in Immunology : This RT emphasizes the immunological mechanisms, novel biomarkers, and therapeutic strategies underpinning celiac disease, with particular relevance to autoimmune and autoinflammatory pathways. Manuscripts not based on-immunological biomarkers, methods or immune outcomes are out of scope. Note on COIs transparency: JS is employed and owns stock in ZymagenX; JT has been a consultant for Dr. Falk Pharma, Teva pharmaceuticals, Anaptysbio, Medpace/ForteBio and PathAi and received personal lecture fees from the Finnish Celiac Society. Topic editors: Juha Taavela, Jack Syage Source: https://www.frontiersin.org/research-topics/87091/advancing-celiac-disease-research-biomarkers-therapeutics-and-patient-centered-outcomes