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疫苗对非典型溶血尿毒症综合征患者 B 群脑膜炎球菌血清型的低疗效。

Low efficacy of vaccination against serogroup B meningococci in patients with atypical hemolytic uremic syndrome.

机构信息

Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.

Department of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, Germany.

出版信息

Biosci Rep. 2020 Mar 27;40(3). doi: 10.1042/BSR20200177.

Abstract

BACKGROUND

The C5 complement inhibitor eculizumab is first-line treatment in atypical hemolytic uremic syndrome (aHUS) going along with a highly increased risk of meningococcal infections. Serogroup B meningococci (MenB) are the most frequently encountered cause for meningococcal infections in Europe. Efficacy of the protein-based MenB-vaccine Bexsero in aHUS has not been determined and testing is only possible in patients off-treatment with eculizumab as a human complement source is required.

METHODS

Patients with aHUS were vaccinated with two doses of the protein-based MenB-vaccine Bexsero. Serum bactericidal antibody (SBA) titers against factor H binding protein (fHbp) of MenB were determined in 14 patients with aHUS off-treatment with eculizumab.

RESULTS

Only 50% of patients showed protective human serum bactericidal antibody (hSBA) titers (≥1:4) against MenB following two vaccinations. Bactericidal antibody titers were relatively low (≤1:8) in three of seven patients with protective titers. While 71% of patients were on immunosuppressive treatment for either thrombotic microangiopathy or renal transplantation at either first or second vaccination, all four patients not receiving any immunosuppressive treatment showed protective bactericidal antibody response. Time between second vaccination and titer measurement was not significantly different between patients with protective titers compared with those with non-protective titers, while time between first and second vaccination was significantly longer in patients with protective titers going along with a tendency for reduction in immunosuppressive treatment.

CONCLUSIONS

Efficacy of vaccination against MenB is insufficient in patients with aHUS. Response to vaccination seems to be hampered by immunosuppression. Therefore, implementation of adequate antibiotic prophylaxis seems pivotal.

摘要

背景

C5 补体抑制剂依库珠单抗是治疗非典型溶血尿毒症综合征(aHUS)的一线药物,但会极大增加患脑膜炎球菌感染的风险。B 群脑膜炎球菌(MenB)是欧洲最常见的脑膜炎球菌感染原因。针对 aHUS 的基于蛋白的 MenB 疫苗 Bexsero 的疗效尚未确定,并且仅在停用依库珠单抗治疗的患者中进行检测,因为需要人补体源。

方法

aHUS 患者接种两剂基于蛋白的 MenB 疫苗 Bexsero。在 14 名停用依库珠单抗治疗的 aHUS 患者中,测定针对 MenB 因子 H 结合蛋白(fHbp)的血清杀菌抗体(SBA)滴度。

结果

仅 50%的患者在两剂接种后显示出针对 MenB 的保护性人血清杀菌抗体(hSBA)滴度(≥1:4)。在具有保护性滴度的七名患者中,有三名的杀菌抗体滴度相对较低(≤1:8)。虽然在第一次或第二次接种时,71%的患者正在接受免疫抑制治疗,用于治疗血栓性微血管病或肾移植,但所有四名未接受任何免疫抑制治疗的患者均显示出保护性杀菌抗体反应。与具有非保护性滴度的患者相比,保护性滴度患者的第二次接种和滴度测量之间的时间没有显著差异,而具有保护性滴度的患者的第一次和第二次接种之间的时间明显更长,同时免疫抑制治疗的强度也呈下降趋势。

结论

在 aHUS 患者中,接种 MenB 的疗效不足。免疫抑制似乎会阻碍对疫苗的反应。因此,实施适当的抗生素预防措施似乎至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ea8/7098122/ecbef47018c1/bsr-40-bsr20200177-g1.jpg

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