Department of Biomedical Sciences and Biotechnologies, 2nd Pediatric Clinic, University of Cagliari, Cagliari, Italy.
Pediatric Clinic, Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, Sassari, Italy.
Biomed Res Int. 2017;2017:3563278. doi: 10.1155/2017/3563278. Epub 2017 Nov 27.
Diagnosis of de novo autoimmune hepatitis (AIH) after orthotopic liver transplantation (OLT) is challenging especially in the 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 -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.
诊断肝移植（OLT）后新诊断的自身免疫性肝炎（AIH）具有挑战性，尤其是在没有高球蛋白血症的情况下。循环自身抗体在新诊断的 AIH 中既不敏感也不特异，但阳性时会增加诊断的可能性。我们报告了一例 9 岁男孩在 OLT 后 7 年发生“新诊断”AIH 时发现的新型肝微粒体（LM）针对 CYP-2C19 的自身抗体。移植物功能障碍表现为高转氨酶血症（高达 400IU/L），而血清球蛋白仍在年龄正常范围内。肝组织学和大剂量泼尼松（2mg/kg/天）加用硫唑嘌呤治疗的反应进一步支持新诊断的 AIH 的诊断。通过在啮齿动物组织上进行间接免疫荧光（IF）对自身抗体进行的研究显示出一种新的染色模式，涉及肝中央区且不影响肾组织。人而非大鼠肝蛋白免疫印迹允许我们对新型 LM 抗体进行特征描述，并鉴定 CYP-2C19 为人抗原。这一发现为关于新诊断的 AIH 的发病机制中自身免疫与同种异体反应的争议性讨论提供了深入了解。通过 IF 以外的方法检测抗体时对人组织与大鼠组织抗原的正确信息可能对 OLT 后患者的正确诊断和管理具有重要意义。
