Beyond gluten-free diet: Novel therapeutic frontiers in celiac disease armamentarium

Table 1 Emerging biomarkers in celiac disease

Biomarker	Biological basis	Clinical application	Diagnostic performance	Ref.
Faecal/urinary GIP	Partially digested gluten fragments in urine/faeces	Objective assessment of GFD adherence; detects recent gluten ingestion	No fixed sensitivity/specificity for gluten exposure (depends on timing of collection; short detection window (24-48 hours)	[41-45]
			Repeated GIP testing correlates with mucosal status but does not independently predict healing
tTG-neo antibodies	Antibodies to neo-epitopes formed by tTG-gliadin complexes	Diagnosis of active CeD	Sensitivity 98%-100%, specificity 93%-96% [vs anti tTG antibodies (sensitivity 74%-100%, specificity 78%-100%)]	[46-48,58]
			Accuracy for detecting villous atrophy in GFD patients: 90%, higher than other serologic tests
HLA DQ2 gliadin tetramer assay	Identifies circulating gluten-specific CD4+ T cells	Diagnosis of CeD even if patients are on GFD	On GFD, sensitivity 97%, specificity 95%	[51]
			On gluten diet, sensitivity 100%, specificity 90%
Serum IL-2 rise post gluten challenge	Rapid cytokine surge reflecting acute gluten-specific T-cell activation	Detects acute gluten exposure	No validated sensitivity/specificity reported yet; consistent IL-2 peak at about 4 hours after gluten ingestion	[52-54]
Circulating microRNAs	Altered expression patterns reflect mucosal injury	Exploratory diagnostic biomarker	No validated sensitivity/specificity	[56,57]

CeD: Celiac disease; GFD: Gluten-free diet; GIP: Gluten immunogenic peptides; tTG: Tissue transglutaminase inhibitor; IL: Interleukin; HLA-DQ2: Human leucocyte antigen-DQ2.