背景:描述过去十年来英格兰发生侵袭性脑膜炎球菌病(IMD)的遗传性和获得性补体缺乏患者。
方法:英国公共卫生部在英国加强IMD监测。我们回顾性地确定了2008-2017年期间在英格兰发展IMD的补体缺乏患者,并检索了他们的临床表现信息。疫苗接种状况,用药史,感染复发和结果,以及感染脑膜炎球菌菌株的特征。
结果:共确定了16例20次IMD发作的患者,包括四集两集.六名患者有遗传性补体缺乏,两人患有与补体缺乏相关的免疫介导疾病(肾小球肾炎和血管炎),另外八人正在接受Eculizumab治疗,阵发性夜间血红蛋白尿症5例,非典型溶血性尿毒综合征3例。在患有遗传性补体缺乏/免疫介导的疾病的患者中,11次发作中的7次可获得培养物,主要包膜组为Y(7/11),其次是B(3/11)和不可分组(1/11)菌株。在接受Eculizumab治疗的患者中,9例发作中有3例归因于B组(3/9),另外三个是NG,但基因型是B组,E组各有一个案例,W和Y.
结论:在英格兰,补体缺乏在IMD病例中罕见,包括晚期补体途径的遗传性疾病,与低补体水平相关的免疫介导疾病和接受Eculizumab治疗的患者。由于包膜Y组引起的IMD在遗传性补体缺乏患者中占主导地位,而接受Eculizumab治疗的患者由于包括非包封菌株在内的更多不同的荚膜组而发展为IMD.
BACKGROUND: To describe patients with inherited and acquired complement deficiency who developed invasive meningococcal disease (IMD) in England over the last decade.
METHODS: Public Health England conducts enhanced surveillance of IMD in England. We retrospectively identified patients with complement deficiency who developed IMD in England during 2008-2017 and retrieved information on their clinical presentation, vaccination status, medication history, recurrence of infection and outcomes, as well as characteristics of the infecting meningococcal strain.
RESULTS: A total of 16 patients with 20 IMD episodes were identified, including four with two episodes. Six patients had inherited complement deficiencies, two had immune-mediated conditions associated with complement deficiency (glomerulonephritis and vasculitis), and eight others were on Eculizumab therapy, five for paroxysmal nocturnal haemoglobinuria and three for atypical haemolytic uraemic syndrome. Cultures were available for 7 of 11 episodes among those with inherited complement deficiencies/immune-mediated conditions and the predominant capsular group was Y (7/11), followed by B (3/11) and non-groupable (1/11) strains. Among patients receiving Eculizumab therapy, 3 of the 9 episodes were due to group B (3/9), three others were NG but genotypically group B, and one
case each of groups E, W and Y.
CONCLUSIONS: In England, complement deficiency is rare among IMD cases and includes inherited disorders of the late complement pathway, immune-mediated disorders associated with low complement levels and patients on Eculizumab therapy. IMD due to capsular group Y predominates in patient with inherited complement deficiency, whilst those on Eculizumab therapy develop IMD due to more diverse capsular groups including non-encapsulated strains.