METHODS: ELISA and neutralisation assays were performed on sera and TBEV PCR assay on sera and cerebrospinal fluid. T cell assays were conducted on peripheral blood the patient and five healthy vaccinated controls.
RESULTS: The patient was admitted to the hospital with headache and fever. He was not vaccinated against TBE but receiving subcutaneous IgG-replacement therapy (IGRT). TBEV IgG antibodies were low-level positive (due to scIGRT), but the TBEV IgM and TBEV neutralisation tests were negative. During hospitalisation his clinical condition deteriorated (Glasgow coma scale 3/15) and he was treated in the ICU with corticosteroids and external ventricular drainage. He was then treated with plasma containing TBEV IgG without apparent side effects. His symptoms improved within a few days and the TBEV neutralisation test converted to positive. Robust CD8+ T cell responses were observed at three and 18-months post-infection, in the absence of B cells. This was confirmed by tetramers specific for TBEV.
CONCLUSIONS: TBEV IgG-positive plasma given to an XLA patient with TBE without evident adverse reactions may have contributed to a positive clinical outcome. Similar approaches could offer a promising foundation for researching therapeutic options for patients with humoral immunodeficiencies. Importantly, a robust CD8+ T cell response was observed after infection despite the lack of B cells and indicates that these patients can clear acute viral infections and could benefit from future vaccination programs.
方法:对血清进行ELISA和中和测定,对血清和脑脊液进行TBEVPCR测定。对患者的外周血和五个健康接种的对照进行T细胞测定。
结果:患者因头痛和发热入院。他未接种TBE疫苗,但接受皮下IgG替代疗法(IGRT)。TBEVIgG抗体呈低水平阳性(由于scIGRT),但TBEVIgM和TBEV中和试验均为阴性.住院期间,他的临床状况恶化(格拉斯哥昏迷评分3/15),并在ICU接受了皮质类固醇和外部脑室引流治疗。然后用含有TBEVIgG的血浆治疗他,没有明显的副作用。他的症状在几天内得到改善,并且TBEV中和测试转变为阳性。在感染后3个月和18个月观察到强烈的CD8+T细胞反应,在没有B细胞的情况下。这通过对TBEV具有特异性的四聚体证实。
结论:对未出现明显不良反应的XLA患者给予TBEVIgG阳性血浆可能有助于临床转归。类似的方法可以为研究体液免疫缺陷患者的治疗选择提供有希望的基础。重要的是,尽管缺乏B细胞,但感染后仍观察到强大的CD8+T细胞应答,这表明这些患者可以清除急性病毒感染,并可从未来的疫苗接种计划中获益.