title: Immunohistochemical Expression of Antitissue Transglutaminase 2 in Tissue Injuries: An Interpretation Beyond Celiac Disease.
abstract: Tissue transglutaminase 2 enzyme plays a diverse role in intracellular and extracellular functioning. Aberrant expression of anti-TG2 antibody has recently been proposed for extraintestinal identification of celiac disease (CeD), but its utility is questionable. To examine whether anti-TG2 immunohistochemical (IHC) staining can be of diagnostic value in identifying extraintestinal involvement in CeD, tissue blocks of patients with IgA nephropathies (IgAN), minimal change disease, membranous glomerulonephritis, membrano-proliferative glomerulonephritis, normal kidney, intestinal biopsies from CeD, tropical sprue, nonspecific duodenitis, and inflammatory bowel disease; liver biopsies from patients with chronic hepatitis B and C, acute liver failure (ALF), and CeD-associated liver diseases were retrieved and subjected to IHC staining for anti-tissue transglutaminase 2 enzyme. H-score was calculated by multiplying the area of positivity and stain intensity. Anti-TG2 stain H-scores were almost similar in IgAN and non-IgANs (H-score 6.31±3 vs. 7.03±2.7); however, H-scores in both of these groups were significantly higher than in normal renal parenchyma (1.6±1.5). Only 6.2% patients with IgAN with anti-TG2 immunostain positivity showed a positive anti-tTG antibody serology and villous abnormalities, suggestive of CeD. Intestinal biopsies from patients with CeD, tropical sprue, nonspecific duodenitis, and inflammatory bowel disease also showed high anti-TG2 H-scores, with no statistically significant differences. Liver biopsies from patients with both ALF, as well as chronic liver diseases showed high anti-TG2 H-scores; with highest stain expression in ALF. In conclusion, IHC expression of anti-TG2 stain correlates with both acute and chronic tissue injuries, irrespective of etiology and organ involvement. It is not a reliable marker for diagnosis of CeD.
authors.affiliation: Departments of Gastroenterology and Human Nutrition, Pathology, and Nephrology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Prasenjit
authors.initials: P
authors.lastname: Das
authors.forename: Ramakant
authors.initials: R
authors.lastname: Rawat
authors.forename: Anil K
authors.initials: AK
authors.lastname: Verma
authors.forename: Geetika
authors.initials: G
authors.lastname: Singh
authors.forename: Archana G
authors.initials: AG
authors.lastname: Vallonthaiel
authors.forename: Rajni
authors.initials: R
authors.lastname: Yadav
authors.forename: Gaurav P S
authors.initials: GPS
authors.lastname: Gahlot
authors.forename: Amit K
authors.initials: AK
authors.lastname: Dinda
authors.forename: Vineet
authors.initials: V
authors.lastname: Ahuja
authors.forename: Siddhartha
authors.initials: S
authors.lastname: Datta Gupta
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Agarwal
authors.forename: Govind K
authors.initials: GK
authors.lastname: Makharia
mesh_terms: D001323:Autoantibodies / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology*; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D002446:Celiac Disease / Q000175:diagnosis* / Q000276:immunology; D019204:GTP-Binding Proteins / Q000276:immunology*; D006525:Hepatitis, Viral, Human / Q000175:diagnosis*; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D007150:Immunohistochemistry; D007674:Kidney Diseases / Q000175:diagnosis*; D011237:Predictive Value of Tests; D011379:Prognosis; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D007070:Immunoglobulin A; C000717608:TGM2 protein, human; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins