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BioMed Research International
Volume 2017, Article ID 3563278, 6 pages
https://doi.org/10.1155/2017/3563278
Research Article

Autoantibodies against CYP-2C19: A Novel Serum Marker in Pediatric De Novo Autoimmune Hepatitis?

1Department of Biomedical Sciences and Biotechnologies, 2nd Pediatric Clinic, University of Cagliari, Cagliari, Italy
2Pediatric Clinic, Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, Sassari, Italy
3Pediatrics, Department of Medicine, Surgery, and Dentistry “Schola Medica Salernitana”, University of Salerno, Baronissi, Salerno, Italy
4Pediatrics Unit, AORN Santobono-Pausilipon, Naples, Italy
5Mediterranean Institute for Transplantation & Advanced Specialized Therapies (ISMETT), Palermo, Italy
6Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany

Correspondence should be addressed to Roberto Antonucci; ti.ssinu@iccunotnar

Received 11 September 2017; Revised 31 October 2017; Accepted 6 November 2017; Published 27 November 2017

Academic Editor: Haruki Komatsu

Copyright © 2017 Maria Grazia Clemente et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Diagnosis of de novo autoimmune hepatitis (AIH) after orthotopic liver transplantation (OLT) is challenging especially in the absence of hyper-γ-globulinemia. Circulating autoantibodies are not sensitive nor specific in de novo AIH but when positive increase the diagnostic probability. We report the discovery of novel liver microsomal (LM) autoantibodies against CYP-2C19 in a 9-year-old boy with “de novo” AIH developed 7 years after OLT. Graft dysfunction presented with hypertransaminasemia (up to 400 IU/L), while serum γ-globulins remained within the normal range for age. Liver histology and response to high dose prednisone (2 mg/kg/day) with the addition of azathioprine therapy further supported the diagnosis of de novo AIH. Autoantibodies investigation by indirect immunofluorescence (IF) on rodent tissues showed a novel staining pattern involving the pericentral liver zone and sparing the renal tissue. Human but not rat liver proteins immunoblotting allowed us to characterize the novel LM antibodies and to identify CYP-2C19 as human antigen. The finding offers insights into the controversial discussion about autoimmunity versus alloreactivity with regard to the pathogenesis of de novo AIH. Correct information on human versus rat tissue antigens tested by methods other than IF for antibodies detection may have significant implications for the correct diagnosis and management of patients followed up after OLT.