Department of Reproductive, Developmental, and Public Health Sciences, University of Trieste, Trieste, Italy.
J Med Virol. 2013 Apr;85(4):716-22. doi: 10.1002/jmv.23525. Epub 2013 Jan 30.
Treatment with biological drugs is associated with increased susceptibility to viral infections. Reactivation of JC virus (JCV) and human cytomegalovirus (HCMV) in adults after therapy has been documented. The long-term effects of biological and conventional therapy on human herpesviruses and polyomaviruses infections in young patients were assessed. One hundred eighty-six samples [urine, serum, and blood cells (PBMCs)] from 62 patients (15.8 ± 6.2 years old) with Crohn's disease, ulcerative rectocolitis or juvenile rheumatoid arthritis treated with immunotherapy or conventional therapy for over 12 months were tested by real time PCR. One hundred twenty-four samples (urine and blood) from 62 matched healthy volunteers (13.8 ± 8.6 years old) were included as controls. Sequencing of the JCV viral protein 1 (VP1) and transcriptional control region (TCR) was performed. Herpes simplex virus 1/2 and varicella zoster virus genomes were not detected in any patients, whereas Epstein-Barr virus, HCMV, and human herpesvirus-6 genomes were detected in 4.8%, 3.2%, and 1.6% of the patients, respectively. JCV was detected in 22.6% (14/62) of urine samples from patients and in 8% (5/62) from controls, in 50% (7/14) of sera from patients shedding JCV, and in 71.4% (5/7) of matched PBMCs. There was a significant association between infliximab treatment and excretion of JCV genotype 2. Subclinical infection/reactivation of JCV genotype 2 in young patients during infliximab therapy was demonstrated. Conversely, increased susceptibility to herpesviruses infection was not shown. Future studies are warranted to investigate the effects of JCV reactivation on the health of young patients treated with infliximab.
治疗生物药物与病毒感染的易感性增加有关。已经证明,成人在治疗后 JC 病毒(JCV)和人类巨细胞病毒(HCMV)的再激活。评估了生物和常规疗法对年轻患者人类疱疹病毒和多瘤病毒感染的长期影响。对 62 例接受免疫治疗或常规治疗超过 12 个月的克罗恩病、溃疡性直肠结肠炎或幼年特发性关节炎患者的 186 份样本(尿液、血清和外周血单个核细胞(PBMCs))[62 名患者(15.8±6.2 岁)]进行了实时 PCR 检测。从 62 名匹配的健康志愿者(13.8±8.6 岁)中选择了 124 份样本(尿液和血液)作为对照。对 JCV 病毒蛋白 1(VP1)和转录调控区(TCR)进行了测序。未在任何患者中检测到单纯疱疹病毒 1/2 和水痘带状疱疹病毒基因组,而在 4.8%、3.2%和 1.6%的患者中分别检测到 EBV、HCMV 和 HHV-6 基因组。在患者的尿液样本中检测到 22.6%(14/62)和对照组中 8%(5/62)的 JCV,在 50%(7/14)的 JCV 脱落血清中,在 71.4%(5/7)的匹配 PBMCs 中。在英夫利昔单抗治疗的患者中,JCV 基因型 2 的排泄与英夫利昔单抗治疗之间存在显著相关性。在英夫利昔单抗治疗期间,年轻患者 JCV 基因型 2 的亚临床感染/再激活得到证实。相反,并未显示出对疱疹病毒感染的易感性增加。需要进一步研究以探讨 JCV 再激活对接受英夫利昔单抗治疗的年轻患者健康的影响。