Double immunohistochemistry to detect transglutaminase 2-IgA deposits in celiac children: a multicentre study

Background: Intestinal transglutaminase 2 (TGM2)-IgA deposits represent an early marker of celiac disease (CeD). Objective: This multicentre retrospective study aimed to assess the usefulness of a double immunohistochemistry technique for detecting TGM2-IgA deposits in formalin-fixed, paraffin-embedded duodenal biopsies from patients with CeD. Methods: Duodenal biopsy sections were classified into: i) CeD, characterized by villous atrophy and serum TGM2 antibodies of IgA class (TGA-IgA) levels categorized as <5 × ULN (low), 5–10 × ULN (moderate), or >10 × ULN (high); ii) Potential CeD (pCeD), defined by normal mucosa with persistently positive TGA-IgA <10 × ULN; iii) Controls, with normal histology and no organic disease. A small cohort of CeD patients was analysed both at diagnosis and after a gluten-free diet. Results: Double immunohistochemistry was performed on 166 CeD, 80 pCeD, and 80 control biopsies. TGM2-IgA deposits were identified in 100% of CeD cases, 72% of pCeD (Marsh 0/1) cases, and in none of the controls. Among 17 CeD patients re-evaluated after a gluten-free diet, all achieved mucosal healing (Marsh 0), 65% showed complete disappearance of deposits, and the remainder a marked reduction. Conclusions: TGM2-IgA double immunohistochemistry may help to refine diagnostic algorithms for CeD diagnosis.