Skip to main content
Top
Published in: Journal of Translational Medicine 1/2018

Open Access 01-12-2018 | Research

Identification of the cellular components involved in de novo immune hepatitis: a quantitative immunohistochemical analysis

Authors: Elena Aguado-Domínguez, Lourdes Gómez, José Manuel Sousa, Miguel Ángel Gómez-Bravo, Antonio Núñez-Roldán, Isabel Aguilera

Published in: Journal of Translational Medicine | Issue 1/2018

Login to get access

Abstract

Background

Diagnosis of de novo immune hepatitis (dnIH) after liver transplantation relies on biopsy findings, with an abundance of plasma cells (PCs) in the inflammatory infiltrates a hallmark of the disease. Very little is known about what other types of immune cells exist in the infiltrates mainly located in the portal areas of the liver tissue.

Methods

We analyzed the composition of T cells, B cells, PCs, and macrophages in the liver biopsies of 12 patients with dnIH, 9 of them obtained at the time of diagnosis. For comparison, biopsies from 9 patients with chronic rejection (CR) were included in the study. The results were analyzed by a computer-assisted stereology quantification method.

Results

The major components of the infiltrates in the portal areas were CD3+ T lymphocytes in both groups, with 36.6% in the dnIH group versus 49.4% in the CR group. CD20+ B lymphocytes represented 14.9% in the dnIH group and 29.1% in the CR group. Macrophage levels were very similar in the dnIH and CR group (19.7% versus 16.8%, respectively). PCs were much less represented in CR biopsies than those from the dnIH group (mean value of 4.7% versus 28.8%).

Conclusion

In conclusion, the determination of a characteristic cellular profile could be an important tool for a more reliable diagnosis of dnIH, in support of the histological evaluation made by the pathologist, which in most cases is challenging. Recognition of this condition is crucial because it leads to graft failure if left untreated.
Appendix
Available only for authorised users
Literature
1.
go back to reference Aguilera I, Sousa JM, Gavilán F, Bernardos A, Wichmann I, Nuñez-Roldán A. Glutathione S-transferase T1 mismatch constitutes a risk factor for de novo immune hepatitis after liver transplantation. Liver Transplant. 2004;10(9):1166–72.CrossRef Aguilera I, Sousa JM, Gavilán F, Bernardos A, Wichmann I, Nuñez-Roldán A. Glutathione S-transferase T1 mismatch constitutes a risk factor for de novo immune hepatitis after liver transplantation. Liver Transplant. 2004;10(9):1166–72.CrossRef
2.
go back to reference Fiel M, Agarwal K, Stanca C, Eihaji N, Kontorinis N, Thung SN. Posttransplant plasma cell hepatitis (de novo autoimmune hepatitis) is a variant of rejection and may lead to a negative outcome in patients with hepatitis C Virus. Liver Transplant. 2008;14(6):861–71.CrossRef Fiel M, Agarwal K, Stanca C, Eihaji N, Kontorinis N, Thung SN. Posttransplant plasma cell hepatitis (de novo autoimmune hepatitis) is a variant of rejection and may lead to a negative outcome in patients with hepatitis C Virus. Liver Transplant. 2008;14(6):861–71.CrossRef
3.
go back to reference Evans HM, Kelly DA, McKiernan PJ, Hübscher S. Progressive histological damage in liver allografts following pediatric liver transplantation. Hepatology. 2006;43(5):1109–17.CrossRef Evans HM, Kelly DA, McKiernan PJ, Hübscher S. Progressive histological damage in liver allografts following pediatric liver transplantation. Hepatology. 2006;43(5):1109–17.CrossRef
4.
go back to reference Aguilera I, Wichmann I, Sousa JM, Bernardos A, Franco E, García-Lozano JR, et al. Antibodies against glutathione S-transferase T1 (GSTT1) in patients with de novo immune hepatitis following liver transplantation. Clin Exp Immunol. 2001;126(3):535–9.CrossRef Aguilera I, Wichmann I, Sousa JM, Bernardos A, Franco E, García-Lozano JR, et al. Antibodies against glutathione S-transferase T1 (GSTT1) in patients with de novo immune hepatitis following liver transplantation. Clin Exp Immunol. 2001;126(3):535–9.CrossRef
5.
go back to reference Aguilera I, Sousa JM, Praena JM, Gómez-Bravo MA, Núñez-Roldán A. Choice of calcineurin inhibitor may influence the development of de novo immune hepatitis associated with anti-GSTT1 antibodies after liver transplantation. Clin Transplant. 2011;25(2):207–12.CrossRef Aguilera I, Sousa JM, Praena JM, Gómez-Bravo MA, Núñez-Roldán A. Choice of calcineurin inhibitor may influence the development of de novo immune hepatitis associated with anti-GSTT1 antibodies after liver transplantation. Clin Transplant. 2011;25(2):207–12.CrossRef
6.
go back to reference Aguilera I, Martinez-Bravo MJ, Sousa JM, Pozo-Borrego AJ, Núñez-Roldán A. IgG subclass profile among anti-Glutathione S-transferase T1 antibodies in post-transplant de novo immune hepatitis. Clin Transplant. 2016;30(3):210–7.CrossRef Aguilera I, Martinez-Bravo MJ, Sousa JM, Pozo-Borrego AJ, Núñez-Roldán A. IgG subclass profile among anti-Glutathione S-transferase T1 antibodies in post-transplant de novo immune hepatitis. Clin Transplant. 2016;30(3):210–7.CrossRef
7.
go back to reference Adeyi O, Fischer SE, Guindi M. Liver allograft pathology: approach to interpretation of needle biopsies with clinicopathological correlation. J Clin Pathol. 2010;63(1):47–74.CrossRef Adeyi O, Fischer SE, Guindi M. Liver allograft pathology: approach to interpretation of needle biopsies with clinicopathological correlation. J Clin Pathol. 2010;63(1):47–74.CrossRef
8.
go back to reference Demetris AJ, Bellamy C, Hübscher SG, O’Leary J, Randhawa PS, Feng S, et al. Comprehensive update of the Banff Working Group on liver allograft pathology: introduction of antibody-mediated rejection. Am J Transplant. 2016;16:2816–35.CrossRef Demetris AJ, Bellamy C, Hübscher SG, O’Leary J, Randhawa PS, Feng S, et al. Comprehensive update of the Banff Working Group on liver allograft pathology: introduction of antibody-mediated rejection. Am J Transplant. 2016;16:2816–35.CrossRef
9.
go back to reference Alexander J, Chu W, Swanson PE, Yeh MM. The significance of plasma cell infiltrate in acute cellular rejection of liver allografts. Hum Pathol. 2012;43(10):1645–50.CrossRef Alexander J, Chu W, Swanson PE, Yeh MM. The significance of plasma cell infiltrate in acute cellular rejection of liver allografts. Hum Pathol. 2012;43(10):1645–50.CrossRef
10.
go back to reference Zhao XY, Rakhda MIA, Wang TI, Jia JD. Immunoglobulin G4-associated de novo autoimmune hepatitis after liver transplantation for chronic hepatitis B- and C-related cirrhosis and hepatocellular carcinoma: a case report with literature review. Transplant Proc. 2013;45(2):824–7.CrossRef Zhao XY, Rakhda MIA, Wang TI, Jia JD. Immunoglobulin G4-associated de novo autoimmune hepatitis after liver transplantation for chronic hepatitis B- and C-related cirrhosis and hepatocellular carcinoma: a case report with literature review. Transplant Proc. 2013;45(2):824–7.CrossRef
11.
go back to reference Castillo-Rama M, Sebagh M, Sasatomi E, Randhawa P, Isse K, Salgarkar AD, et al. “Plasma cell hepatitis” in liver allografts: identification and characterization of an IgG4-rich cohort. Am J Transplant. 2013;13(11):2966–77.CrossRef Castillo-Rama M, Sebagh M, Sasatomi E, Randhawa P, Isse K, Salgarkar AD, et al. “Plasma cell hepatitis” in liver allografts: identification and characterization of an IgG4-rich cohort. Am J Transplant. 2013;13(11):2966–77.CrossRef
12.
go back to reference Hadžić N, Quaglia A, Cotoi C, Hussain MJ, Brown N, Vergani D, et al. Immunohistochemical phenotyping of the inflammatory infiltrate in de novo autoimmune hepatitis after liver transplantation in children. Pediatr Transplant. 2012;16(5):501–10.CrossRef Hadžić N, Quaglia A, Cotoi C, Hussain MJ, Brown N, Vergani D, et al. Immunohistochemical phenotyping of the inflammatory infiltrate in de novo autoimmune hepatitis after liver transplantation in children. Pediatr Transplant. 2012;16(5):501–10.CrossRef
13.
go back to reference Pongpaibul A, Vernik R, McDiarmid S, Lassman C. Histopathology of de novo autoimmune hepatitis. Liver Transplant. 2012;18:811–8.CrossRef Pongpaibul A, Vernik R, McDiarmid S, Lassman C. Histopathology of de novo autoimmune hepatitis. Liver Transplant. 2012;18:811–8.CrossRef
14.
go back to reference Gärtner V, Eigentler TK, Viebahn R. Plasma cell-rich rejection processes in renal transplantation: morphology and prognostic relevance. Transplantation. 2006;81(7):986–91.CrossRef Gärtner V, Eigentler TK, Viebahn R. Plasma cell-rich rejection processes in renal transplantation: morphology and prognostic relevance. Transplantation. 2006;81(7):986–91.CrossRef
15.
go back to reference Nádasdy T, Krenács T, Kalmár KN, Csajbók E, Boda K, Ormos J. Importance of plasma cells in the infiltrate of renal allografts. Pathol Res Pract. 1991;187(2–3):178–83.CrossRef Nádasdy T, Krenács T, Kalmár KN, Csajbók E, Boda K, Ormos J. Importance of plasma cells in the infiltrate of renal allografts. Pathol Res Pract. 1991;187(2–3):178–83.CrossRef
16.
go back to reference Charney DA, Nadasdy T, Lo AW, Racusen LC. Plasma cell-rich acute renal allograft rejection. Transplantation. 1999;68(6):791–7.CrossRef Charney DA, Nadasdy T, Lo AW, Racusen LC. Plasma cell-rich acute renal allograft rejection. Transplantation. 1999;68(6):791–7.CrossRef
17.
go back to reference Desvaux D, Le Gouvello S, Pastural M, Abtahi M, Suberbielle C, Boeri N, et al. Acute renal allograft rejections with major interstitial oedema and plasma cell-rich infiltrates: high gamma-interferon expression and poor clinical outcome. Nephrol Dial Transplant. 2004;19(4):933–9.CrossRef Desvaux D, Le Gouvello S, Pastural M, Abtahi M, Suberbielle C, Boeri N, et al. Acute renal allograft rejections with major interstitial oedema and plasma cell-rich infiltrates: high gamma-interferon expression and poor clinical outcome. Nephrol Dial Transplant. 2004;19(4):933–9.CrossRef
Metadata
Title
Identification of the cellular components involved in de novo immune hepatitis: a quantitative immunohistochemical analysis
Authors
Elena Aguado-Domínguez
Lourdes Gómez
José Manuel Sousa
Miguel Ángel Gómez-Bravo
Antonio Núñez-Roldán
Isabel Aguilera
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2018
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-018-1440-8

Other articles of this Issue 1/2018

Journal of Translational Medicine 1/2018 Go to the issue