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

Maria Grazia Clemente, Roberto Antonucci, Claudia Mandato, Lucia Cicotto, Antonella Meloni, Bruno Gridelli, Stefano De Virgiliis, Michael P Manns, Pietro Vajro

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)3563278
JournalBioMed Research International
Volume2017
DOIs
Publication statusPublished - 2017

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Autoimmune Hepatitis
Pediatrics
Liver
Autoantibodies
Biomarkers
Liver Transplantation
Tissue
Antigens
Serum Globulins
Antibodies
Azathioprine
Rats
Indirect Fluorescent Antibody Technique
Prednisone
Autoimmunity
Immunoblotting
Fluorescent Antibody Technique
Rodentia
Histology
Reference Values

Keywords

  • Journal Article

Cite this

Clemente, M. G., Antonucci, R., Mandato, C., Cicotto, L., Meloni, A., Gridelli, B., ... Vajro, P. (2017). Autoantibodies against CYP-2C19: A Novel Serum Marker in Pediatric De Novo Autoimmune Hepatitis? BioMed Research International, 2017, 3563278. https://doi.org/10.1155/2017/3563278

Autoantibodies against CYP-2C19 : A Novel Serum Marker in Pediatric De Novo Autoimmune Hepatitis? / Clemente, Maria Grazia; Antonucci, Roberto; Mandato, Claudia; Cicotto, Lucia; Meloni, Antonella; Gridelli, Bruno; De Virgiliis, Stefano; Manns, Michael P; Vajro, Pietro.

In: BioMed Research International, Vol. 2017, 2017, p. 3563278.

Research output: Contribution to journalArticle

Clemente, MG, Antonucci, R, Mandato, C, Cicotto, L, Meloni, A, Gridelli, B, De Virgiliis, S, Manns, MP & Vajro, P 2017, 'Autoantibodies against CYP-2C19: A Novel Serum Marker in Pediatric De Novo Autoimmune Hepatitis?', BioMed Research International, vol. 2017, pp. 3563278. https://doi.org/10.1155/2017/3563278
Clemente, Maria Grazia ; Antonucci, Roberto ; Mandato, Claudia ; Cicotto, Lucia ; Meloni, Antonella ; Gridelli, Bruno ; De Virgiliis, Stefano ; Manns, Michael P ; Vajro, Pietro. / Autoantibodies against CYP-2C19 : A Novel Serum Marker in Pediatric De Novo Autoimmune Hepatitis?. In: BioMed Research International. 2017 ; Vol. 2017. pp. 3563278.
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