Add-On: Celiac Panel

Tissue transglutaminase 2 is a ubiquitous enzyme that deamidates gliadin peptides in the lamina propria, creating neo-epitopes recognised by HLA-DQ2 or HLA-DQ8 restricted T cells in genetically susceptible individuals. The resulting adaptive immune response generates IgA antibodies to both gliadin and tissue transglutaminase itself. These antibodies are highly sensitive and specific markers of active mucosal damage in coeliac disease and disappear on a strict gluten-free diet, making tTG-IgA the cornerstone serological test.

tTG-IgA is the single most sensitive and specific serological marker for coeliac disease and the recommended first-line test in guidelines from the British Society of Gastroenterology and the American College of Gastroenterology. A positive result in a patient consuming gluten strongly supports the diagnosis and prompts duodenal biopsy; a negative result in an IgA-sufficient patient makes active coeliac disease unlikely.

Immunoglobulin A is the dominant antibody class at mucosal surfaces and the second most abundant immunoglobulin in serum. Selective IgA deficiency, present in roughly 1 in 300–700 individuals, renders IgA-based coeliac serology falsely negative, so total IgA must be measured alongside tTG-IgA to identify affected patients who require IgG-based tests.

Total IgA serves as a control for the validity of IgA-based coeliac serology. A low or absent IgA invalidates a negative tTG-IgA result and necessitates IgG tests — either deamidated gliadin peptide IgG or tTG-IgG — to rule out coeliac disease in that patient.

Endomysial antibodies recognise tissue transglutaminase epitopes displayed on smooth-muscle endomysium, detected by indirect immunofluorescence on monkey oesophagus or human umbilical cord. The target antigen is the same as tTG, so EMA-IgA and tTG-IgA correlate closely, but EMA is operator-dependent and more labour-intensive.

EMA-IgA is highly specific for coeliac disease — approaching 100 per cent in many series — and historically was the reference standard. Today it is used as a confirmatory test when tTG-IgA is weakly positive or the clinical picture is ambiguous, and in paediatric protocols where a very high EMA titre can obviate biopsy in selected cases.

Deamidated gliadin peptides are generated by tissue transglutaminase and are more immunogenic than native gliadin. IgG antibodies to these peptides have improved sensitivity and specificity over older anti-gliadin tests and are particularly useful in IgA-deficient patients and in young children under two years, in whom IgA responses may be immature.

DGP-IgG complements tTG-IgA in two settings: as the primary serological marker in patients with selective IgA deficiency, and in very young children where both DGP-IgG and DGP-IgA may be positive before tTG-IgA becomes detectable. It is less specific than tTG-IgA in the general population, so interpretation must account for clinical context.