Clinical meaning
The celiac disease workup follows a systematic algorithm: screen with serum tTG-IgA (tissue transglutaminase IgA, >95% sensitivity and specificity) plus total serum IgA (to exclude IgA deficiency causing false negatives). If tTG-IgA is positive, refer for upper endoscopy with duodenal biopsies (at least 4-6 from the second/third part of duodenum plus 1-2 from the duodenal bulb). Histological findings are graded by the Marsh classification: Marsh 0 (normal), Marsh 1 (increased intraepithelial lymphocytes >25 per 100 enterocytes), Marsh 2 (IEL increase plus crypt hyperplasia), Marsh 3a-c (partial to total villous atrophy with crypt hyperplasia and IEL increase). Critically, the patient MUST be consuming gluten at the time of serological testing and biopsy — a premature gluten-free diet causes false-negative results and invalidates the workup. If tTG-IgA is negative but clinical suspicion remains high, check total IgA level; if IgA deficient, order IgG-based tests (tTG-IgG, DGP-IgG). HLA-DQ2/DQ8 genotyping has >99% negative predictive value and is useful to rule out celiac disease in uncertain cases.