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Autoantibodies against CYP-2C19: a novel serum marker in pediatric de-novo autoimmune hepatitis?

Clemente, Maria Grazia and Antonucci, Roberto and Mandato, Claudia and Cicotto, Lucia and Meloni, Antonella and Gridelli, Bruno and De Virgiliis, Stefano and Manns, Michael P. and Vajro, Pietro (2017) Autoantibodies against CYP-2C19: a novel serum marker in pediatric de-novo autoimmune hepatitis? BioMed Research International, Vol. 2017 (ID 3563278), p. 6. ISSN 2314-6133. Article.

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DOI: 10.1155/2017/3563278

Abstract

Diagnosis of de-novo autoimmune hepatitis (AIH) after orthotopic liver transplantation (OLT) is challenging especially in absence of hyper--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 (2mg/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 immunoblottings 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.

Item Type:Article
ID Code:11838
Status:Published
Refereed:Yes
Uncontrolled Keywords:Anti-liver microsomal autoantibodies, anti-liver cytosol autoantibodies, CYP, drug-induced hepatitis, biliary atresia, autoimmune liver disease, allo-immune response, liver graft dysfunction
Subjects:Area 06 - Scienze mediche > MED/38 Pediatria generale e specialistica
Divisions:001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Scienze Chirurgiche, Microchirurgiche e Mediche
Publisher:Hindawi Publishing Corporation
ISSN:2314-6133
Copyright Holders:© 2017 Maria Grazia Clemente et al.
Deposited On:13 Dec 2017 10:55

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