Duodenum Mukozasında Tim-3 Ekspresyonu: Çölyak Hastalığının Patogenezinde ve Tanısında İmmün Kontrol Noktası Molekülü Olarak Rolü

Öz

Çölyak hastalığında (ÇH) immün kontrol noktası moleküllerinin (İKM) ekspresyonuna ilişkin sınırlı veri bulunmaktadır. Bu çalışmada, ÇH hastalarına ve bazılarında intraepitelyal lenfosit (İEL) artışı olan ÇH olmayan hastalara ait duodenum biyopsilerinde Tim-3 ekspresyonunun değerlendirilmesi amaçlandı. Yetişkin gastroenteroloji kliniğine başvuran 214 bireyin duodenal dokuları yeniden değerlendirildi. Amerikan Gastroenteroloji Koleji Kılavuzları, ÇH tanısını doğrulamak için kullanıldı. İmmünohistokimyasal analizler için formalinle fikse edilmiş parafine gömülmüş duodenum dokularından kesitler hazırlandı. Lamina propriada en yüksek Tim-3 ekspresyonuna sahip alan 40x (BBA) büyütmede sayıldı. Receiver Operating Characteristic analizi, ÇH tanısını "BBA başına >9" (p<0.001, AUC: 0.744) olarak öngören bir kesme değeri sundu. Yüksek Tim-3 ekspresyonu, daha yüksek İEL ve ÇH tanısı ile ilişkiliydi ve tüm kohortta ÇH'nin endoskopik ve serolojik bulgularıyla korele idi (p<0.001). ÇH grubunda, Tim-3 pozitif hücre sayıları ile ortalama İEL sayıları arasında bir korelasyon bulundu (p=0.007, Spearman'ın rho: 0.279). Diğer taraftan, ÇH hastalarında Tim-3 ekspresyonu ile Marsh tipleri (p=0.291), serum tTG (p=0.482) ve EMA (p=0.765) titreleri arasında bir fark tespit edilmedi. ÇH olmayan grupta, Tim-3 ekspresyonu İEL'deki artıştan ve gastrik Helicobacter pylori enfeksiyonundan etkilenmemiştir. Bu çalışmada, Tim-3'ün bir İKM olarak duodenum mukozasındaki ekspresyon profilini ilk kez gösterdik. Bu bulguların daha ileri analizlerle doğrulanması, duodenum mukozasındaki inflamatuar döngünün daha iyi anlaşılmasına ve ÇH hastalarının tanısında ve patogenezinin anlaşılmasında yeni bakış açılarına olanak sağlayacaktır.

Anahtar Kelimeler

• Çölyak hastalığı
• İmmün kontrol noktası molekülü
• İntraepitelyal lenfosit
• Tim-3

Tim-3 Expression in Duodenal Mucosa: The Role in the Pathogenesis and Diagnosis of Celiac Disease As An İmmune Checkpoint Molecule

Öz

Limited data exist on the expression of immune checkpoint molecules (ICMs) in celiac disease (CD). This study aims to evaluate Tim-3 expression in duodenal biopsies from CD patients and those of non-CD patients, some of whom have increased intraepithelial lymphocytes (IELs). Duodenal tissues from 214 individuals who applied to the adult gastroenterology clinic were re-evaluated. The American College of Gastroenterology Guidelines were used to confirm the diagnosis of CD. Sections were prepared from formalin-fixed paraffin-embedded duodenal tissues for immunohistochemical analyses. The area with the highest Tim-3 expression in the lamina propria was counted at 40x (HPF) magnification. Receiver operating characteristic analysis offered a cut-off value predicting CD diagnosis as “>9 per HPF” (p<0.001, AUC: 0.744). High Tim-3 expression was associated with higher IEL numbers and a diagnosis of CD and correlated with endoscopic and serological findings of CD (p<0.001) in the whole cohort. In the CD group, a correlation was found between Tim-3 positive cell numbers and mean IEL counts (p=0.007, Spearman’s rho: 0.279). On the other hand, no difference was detected between Tim-3 expression and Marsh types (p=0.291), serum tTG (p=0.482), and EMA (p=0.765) titers in CD patients. In the non-CD group, Tim-3 expression was unaffected by either the increase in IEL or gastric Helicobacter pylori infection. In this study, we first demonstrated the expression profile of Tim-3 in the duodenal mucosa as an ICM. Confirmation of these findings with further analyses will provide a better understanding of the inflammatory cycle in the duodenal mucosa and new insights into diagnosing and understanding CD pathogenesis.

Anahtar Kelimeler

• Celiac disease
• Immune checkpoint molecule
• Intraepithelial lymphocyte
• Tim-3

Kaynakça

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