title: Titers of anti-tissue transglutaminase antibody correlate well with severity of villous abnormalities in celiac disease.
abstract: OBJECTIVE
  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.
  
  
  BACKGROUND
  Guidelines for diagnosing CeD suggest that biopsy could be avoided in some patients with high anti-tTG ab titer.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Departments of *Gastroenterology and Human Nutrition †Pathology ‡Biostatistics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Prashant
authors.initials: P
authors.lastname: Singh
authors.forename: Lalit
authors.initials: L
authors.lastname: Kurray
authors.forename: Abhishek
authors.initials: A
authors.lastname: Agnihotri
authors.forename: Prasenjit
authors.initials: P
authors.lastname: Das
authors.forename: Anil Kumar
authors.initials: AK
authors.lastname: Verma
authors.forename: Vishnubhatla
authors.initials: V
authors.lastname: Sreenivas
authors.forename: Siddharth
authors.initials: S
authors.lastname: Dattagupta
authors.forename: Govind K
authors.initials: GK
authors.lastname: Makharia
mesh_terms: D000293:Adolescent; D000328:Adult; D001284:Atrophy; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D002446:Celiac Disease / Q000097:blood / Q000175:diagnosis* / Q000178:diet therapy / Q000276:immunology / Q000473:pathology; D055050:Diet, Gluten-Free; D004386:Duodenum / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019204:GTP-Binding Proteins / Q000276:immunology*; D006801:Humans; D007194:India; D008297:Male; D008871:Microvilli / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012189:Retrospective Studies; D012720:Severity of Illness Index; D011503:Transglutaminases / Q000276:immunology*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins