A new algorithm for coeliac disease based on the 'long forgotten' TCRγδ⁺ intra-epithelial lymphocytes detected with...

Diagnosis of coeliac disease (CD) with mild mucosal changes is difficult for all parties involved. We aimed to determine the power of T cell receptor (TCR)γδ⁺ intra-epithelial lymphocytes (IELs) in discriminating CD from other causes of intra-epithelial lymphocytosis using a new monoclonal antibody.

A total of 167 cases categorised as coeliac (117 untreated CD, classified according to Marsh, updated by Ensari, including 29 type 1, 29 type 2, 39 type 3 and 20 treated CD), and non-coeliac groups (24 controls and 26 non-coeliac IELosis) based on clinical, serological and histological data were studied for IEL counts enumerated per 100 enterocytes using haematoxylin and eosin, CD3, TCR δ-stains.

TCRγδ⁺ IELs were significantly higher in CD (24.83 ± 16.13) compared to non-CD (6.72 ± 6.32) and were correlated with the degree of mucosal damage. Both γδ⁺ IEL count and ratio showed higher performance in differentiating untreated coeliacs from controls, with a sensitivity of 83.76; 85.57 and specificity of 95.83; 79.17, respectively. TCRγδ⁺ IEL counts distinguished type 1 CD (20.41 ± 13.57) from non-coeliac IELosis (9.42 ± 7.28) (p = 0.025). Discriminant analysis revealed that villus/crypt ratio, γδ⁺ and CD3⁺ IEL counts, γδ⁺/CD3⁺IEL ratio, IEL distribution pattern were potent discriminants and correctly classified 82.3% of cases while the algorithm accurately diagnosed 93.4% of cases.

The new antibody detecting γδ⁺ IELs in FFPE sections revealed thresholds of 10.5 for γδ⁺ IELs and 14% for γδ⁺/CD3⁺IEL ratio which distinguished coeliacs from non-coeliacs with high sensitivity and specificity, particularly in cases with normal villus/crypt axis including type 1 CD, non-CD IELosis and controls. A 'coeliac algorithm' based on γδ⁺ IELs is proposed with the hope that it will be used in the histopathological diagnostic approach by the pathology community.