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We reviewed our celiac disease (CeD) database to study if anti-tissue transglutaminase (tTG) antibody (ab) titers correlate with severity of villous abnormalities in Indian patients and to find out a cutoff value of anti-tTG ab fold-rise, which could best predict CeD.Guidelines for diagnosing CeD suggest that biopsy could be avoided in some patients with high anti-tTG ab titer.We reviewed a cohort of 366 anti-tTG ab–positive individuals in whom duodenal biopsies were performed. Anti-tTG ab was obtained before initiation of gluten-free diet. Anti-tTG ab results were expressed in terms of fold-rise by calculating ratio of observed values with cutoff value. CeD was diagnosed if in addition to positive serology, patients had villous atrophy (>Marsh grade 2) and unequivocal response to gluten-free diet.The mean anti-tTG fold-rise in groups with Marsh grade ≤2 was 2.6 (±2.5), grade 3a was 4.0 (±3.9), 3b was 5.7 (±5.1), and 3c was 11.8 (±8.0). The positive likelihood ratio for diagnosing CeD was 15.4 and 27.4 at 12- and 14-fold-rise of anti-tTG ab titer, respectively. The positive predictive value of diagnosis of CeD was 100% when anti-tTG ab titer was 14-fold higher over the cutoff value. Fifty-seven (43.9%) individuals with anti-tTG titer rise <2-fold high also had CeD.As severity of villous abnormality increases, titer of anti-tTG also rises. Presence of villous atrophy can be predicted at very high anti-tTG ab titer. In contrast to emerging belief, mucosal biopsies should be performed even if anti-tTG ab titer is <2 times, because many patients with CeD have low titers.