Autilio Chiara, Pecoraro Raffaele, Pafundi Vito, Manieri Sergio, Tipo Vincenzo, Martemucci Luigi, Carbone Teresa
Regional San Carlo Hospital, Clinical Pathology and Microbiology Unit, Potenza, Italy.
Department of Biochemistry and Molecular Biology, Complutense University, Madrid, Spain.
Ital J Pediatr. 2025 Jul 3;51(1):208. doi: 10.1186/s13052-025-02029-0.
Anti-fibrillarin autoantibodies (AFA) as serological hallmarks of systemic sclerosis, mainly react with epitopes arranged in the NH2-(aa-1-80) and COOH-terminal-(aa-276-321)-domains of fibrillarin. Interestingly, the fibrillarin NH2-hexapeptide sequence is shared with an Epstein-Barr-virus (EBV)-encoded nuclear antigen.
We herein report a case of a 14-year-old girl presenting with a history of vomiting, sore throat, arthralgias and fever. Laboratory tests revealed leukocytosis, an increased level of CRP, transaminases and total/direct bilirubin. On further investigation, a positivity of ANA testing showing a clumpy nucleolar indirect immunofluorescence (AC-9) pattern on HEp-2000 substrate, due to anti-fibrillarin antibodies, was found. Concomitantly, high concentrations of EBV-VCA-IgM and a slight increase of EBV-VCA-IgG were detected, helping establish a diagnosis of ongoing EBV infection. After a follow-up of six months, all autoimmunity tests were repeated, and together with infection resolution, the negativity of ANA was determined, confirming the transient nature of the autoimmune phenomenon.
Our findings confirm how molecular mimicry plays an important role in the viral-induced autoimmunity. Given the significant homology between fibrillarin and EBV protein sequences, caution in interpreting AFA positivity is suggested, especially in pediatric patients without clinical evidences of an autoimmune condition, and a simultaneous screening for EBV infections is recommended.
抗核仁纤维蛋白自身抗体（AFA）作为系统性硬化症的血清学标志，主要与核仁纤维蛋白氨基端（氨基酸1 - 80）和羧基端（氨基酸276 - 321）结构域中的表位发生反应。有趣的是，核仁纤维蛋白的氨基端六肽序列与爱泼斯坦 - 巴尔病毒（EBV）编码的核抗原相同。
我们在此报告一例14岁女孩，有呕吐、咽痛、关节痛和发热病史。实验室检查显示白细胞增多、CRP、转氨酶及总胆红素/直接胆红素水平升高。进一步检查发现，抗核抗体检测呈阳性，在HEp - 2000底物上显示出团块状核仁间接免疫荧光（AC - 9）模式，原因是存在抗核仁纤维蛋白抗体。同时，检测到高浓度的EBV - VCA - IgM以及EBV - VCA - IgG略有升高，有助于确诊正在发生的EBV感染。随访6个月后，重复所有自身免疫检测，随着感染消退，抗核抗体转阴，证实了自身免疫现象的短暂性。
我们的研究结果证实了分子模拟在病毒诱导的自身免疫中发挥重要作用。鉴于核仁纤维蛋白与EBV蛋白序列之间存在显著同源性，建议在解读AFA阳性结果时谨慎，尤其是对于无自身免疫疾病临床证据的儿科患者，同时建议进行EBV感染的筛查。
