A new algorithm for coeliac disease based on the ‘long forgotten’ TCRγδ+ intra-epithelial lymphocytes detected with an antibody working on FFPE sections


Kozan E. N., Kırmızı B. A., Tuna Kırsaçlıoğlu C., Gökmen D., Savaş B., Kansu Tanca A., ...Daha Fazla

Histopathology, cilt.86, sa.3, ss.397-409, 2025 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 86 Sayı: 3
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1111/his.15330
  • Dergi Adı: Histopathology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, Veterinary Science Database
  • Sayfa Sayıları: ss.397-409
  • Anahtar Kelimeler: coeliac disease, intra-epithelial lymphocytes, T cell receptor gamma delta
  • Ankara Üniversitesi Adresli: Evet

Özet

Aims: 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. Methods: 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. Results: 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. Conclusions: 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.