Hepatic expression of programmed death-1 (PD-1) and its ligand, PD-L1, in children with autoimmune hepatitis: relation to treatment response

Hala Agina; Nermine Ehsan; Taghreed Abd-Elaziz; Ghada Abd-Elfatah; Eman Said; Mostafa Sira

doi:10.5114/ceh.2019.87642

eISSN: 2449-8238
ISSN: 2392-1099

Clinical and Experimental Hepatology

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abstract:

Original paper

Hepatic expression of programmed death-1 (PD-1) and its ligand, PD-L1, in children with autoimmune hepatitis: relation to treatment response

Hala A. Agina

¹

,

Nermine A. Ehsan

²

,

Taghreed A. Abd-Elaziz

¹

,

Ghada A. Abd-Elfatah

¹

,

Eman M. Said

¹

,

Mostafa M. Sira

³

Pathology Department, Faculty of Medicine, Benha University, Egypt
Pathology Department, National Liver Institute, Menoufia University, Egypt
Pediatric Hepatology, Gastroenterology and Nutrition Department, National Liver Institute, Menoufia University, Egypt

Clin Exp HEPATOL 2019; 5, 3: 256–264

DOI: https://doi.org/10.5114/ceh.2019.87642

Online publish date: 2019/09/05

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AMA

Agina HA, Ehsan NA, Abd-Elaziz TA, Abd-Elfatah GA, Said EM, Sira MM. Hepatic expression of programmed death-1 (PD-1) and its ligand, PD-L1, in children with autoimmune hepatitis: relation to treatment response. Clinical and Experimental Hepatology. 2019;5(3):256-264. doi:10.5114/ceh.2019.87642.

APA

Agina, H. A., Ehsan, N. A., Abd-Elaziz, T. A., Abd-Elfatah, G. A., Said, E. M.,  & Sira, M. M. (2019). Hepatic expression of programmed death-1 (PD-1) and its ligand, PD-L1, in children with autoimmune hepatitis: relation to treatment response. Clinical and Experimental Hepatology, 5(3), 256-264. https://doi.org/10.5114/ceh.2019.87642

Chicago

Agina, Hala A, Nermine A Ehsan, Taghreed A Abd-Elaziz, Ghada A Abd-Elfatah, Eman M Said,  and Mostafa M Sira. 2019. "Hepatic expression of programmed death-1 (PD-1) and its ligand, PD-L1, in children with autoimmune hepatitis: relation to treatment response". Clinical and Experimental Hepatology 5 (3): 256-264. doi:10.5114/ceh.2019.87642.

Harvard

Agina, H., Ehsan, N., Abd-Elaziz, T., Abd-Elfatah, G., Said, E.,  and Sira, M. (2019). Hepatic expression of programmed death-1 (PD-1) and its ligand, PD-L1, in children with autoimmune hepatitis: relation to treatment response. Clinical and Experimental Hepatology, 5(3), pp.256-264. https://doi.org/10.5114/ceh.2019.87642

MLA

Agina, Hala et al. "Hepatic expression of programmed death-1 (PD-1) and its ligand, PD-L1, in children with autoimmune hepatitis: relation to treatment response." Clinical and Experimental Hepatology, vol. 5, no. 3, 2019, pp. 256-264. doi:10.5114/ceh.2019.87642.

Vancouver

Agina H, Ehsan N, Abd-Elaziz T, Abd-Elfatah G, Said E, Sira M. Hepatic expression of programmed death-1 (PD-1) and its ligand, PD-L1, in children with autoimmune hepatitis: relation to treatment response. Clinical and Experimental Hepatology. 2019;5(3):256-264. doi:10.5114/ceh.2019.87642.

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Aim of the study
Autoimmune hepatitis (AIH) is characterized histologically by aggressive inflammation with interface hepatitis and prominent lymphoplasmacytic infiltration. Programmed death-1 (PD-1) is expressed on activated lymphocytes. Engagement of PD-1 by its ligand PD-L1 leads to cell apoptosis and death. We aimed to evaluate the immunohistochemical expression of PD-1 and PD-L1 in children with AIH, and its relation to treatment outcome.

Material and methods
Pre-treatment liver biopsies of 31 children with AIH were compared to 30 children with chronic hepatitis C virus (HCV) infection as a control group. PD-1 was evaluated in lymphocytes, while PD-L1 was evaluated in lymphocytes, hepatocytes, biliary epithelial cells, sinusoidal endothelial cells and Kupffer cells. All AIH patients received the standard treatment.

Results
The mean PD-1 was significantly higher in AIH than HCV patients (29.19 ±18.5% vs. 15.2 ±10.1%; p = 0.002) while there was no statistically significant difference as regards PD-L1 on lymphocytes (p = 0.853). Neither PD-1 nor PD-L1 correlated with either liver fibrosis or the inflammatory activity (p > 0.05 for all). PD-1/PD-L1 ratio was significantly higher in AIH compared to HCV patients and in non-responder AIH patients compared to responders (46.9 vs. 6.58). PD-1 expression was comparable in both responders and non-responders (p = 0.813), while PD-L1 was significantly upregulated in responders (4.17 ±3.15% vs. 0.63 ±1.3%; p = 0.046). PD-L1 expression on hepatocytes, biliary epithelial cells, sinusoidal endothelial cells and Kupffer cells was comparable in AIH and HCV groups.

Conclusions
PD-1/PD-L1 ratio, which reflects immune aggression, was significantly higher in AIH compared to HCV patients and in non-responder AIH patients compared to responders.

keywords:

Hepatic expression of programmed death-1 (PD-1) and its ligand, PD-L1, in children with autoimmune hepatitis: relation to treatment response

Hala A. Agina 1 , Nermine A. Ehsan 2 , Taghreed A. Abd-Elaziz 1 , Ghada A. Abd-Elfatah 1 , Eman M. Said 1 , Mostafa M. Sira 3

autoimmune hepatitis, immunohistochemistry, hepatitis C virus, programmed death-1, programmed death ligand-1

Hala A. Agina

¹

,

Nermine A. Ehsan

²

,

Taghreed A. Abd-Elaziz

¹

,

Ghada A. Abd-Elfatah

¹

,

Eman M. Said

¹

,

Mostafa M. Sira

³