Department of Clinical Sciences Lund, Section of Infection Medicine, Lund University, and Skåne University Hospital, Lund, Sweden.
Clinical Immunology and Transfusion Medicine, Region Skåne, Lund, Sweden; Department of Laboratory Medicine, Section of Microbiology, Immunology and Glycobiology, Lund University, Lund, Sweden.
Vaccine. 2021 Feb 22;39(8):1297-1302. doi: 10.1016/j.vaccine.2021.01.007. Epub 2021 Jan 25.
Deficiencies of C2 and other components of the classical pathway of complement are associated with increased risk of infections with encapsulated bacteria, such as Haemophilus (H.) influenzae. Defense against H. influenzae is dependent on specific antibodies and complement, which mediate serum bactericidal activity (SBA) and opsonization. Due to lack of normal classical and lectin complement pathway function in C2 deficiency (C2D), SBA would have to depend either on the alternative pathway or on C2 bypass mechanisms. Here we studied SBA against H. influenzae type b (Hib) before and after vaccination in a group of C2-deficient persons, as the bactericidal capacity of antibodies in autologous complement in relation to vaccination has not been investigated at group level in C2D. Sera from 22 persons with C2D and 26 healthy controls were available. Out of these, 18 persons with C2D and all controls had been vaccinated with Act-HIB®. SBA against Hib bacteria was analyzed with autologous serum as the only complement source. Antibodies to Hib capsular polysaccharide had been analyzed previously. Concentrations of mannose-binding lectin (MBL) and other complement components were measured in serum. SBA of both C2-deficient persons and controls was significantly more efficient after vaccination (p = 0.002 and p < 0.0001, respectively). After vaccination, all but two C2-deficient sera and one control serum showed sufficient SBA (<50% surviving bacteria). Before vaccination, SBA of C2-deficient sera was negatively correlated to serum concentrations of MBL (lower proportion of surviving bacteria with higher MBL concentration; r = -0.55, p = 0.008). After vaccination, SBA of C2-deficient sera was negatively correlated to serum concentrations of IgG Hib antibodies (r = -0.56, p = 0.01). In conclusion, SBA against Hib in autologous serum is increased after vaccination in persons with C2D. In unvaccinated C2-deficient persons SBA was correlated to MBL concentration, providing further support for an MBL-dependent C2 bypass mechanism operating in C2D.
C2 及补体经典途径其他成分的缺乏与荚膜细菌（如流感嗜血杆菌（H.））感染风险增加有关。针对 H. influenzae 的防御依赖于特定的抗体和补体，其介导血清杀菌活性（SBA）和调理作用。由于 C2 缺乏症（C2D）中正常的经典和凝集素补体途径功能缺失，SBA 将不得不依赖替代途径或 C2 旁路机制。在此，我们研究了一组 C2 缺乏症患者在接种疫苗前后针对乙型流感嗜血杆菌（Hib）的 SBA，因为在 C2D 中尚未在组水平上研究过与疫苗接种相关的自体补体抗体的杀菌能力。有 22 名 C2D 患者和 26 名健康对照者的血清可供使用。其中，18 名 C2D 患者和所有对照者均已接种 Act-HIB®。使用自体血清作为唯一的补体来源分析针对 Hib 细菌的 SBA。此前已分析了针对 Hib 荚膜多糖的抗体。在血清中测量了甘露聚糖结合凝集素（MBL）和其他补体成分的浓度。接种疫苗后，C2 缺乏症患者和对照组的 SBA 均明显更有效（分别为 p=0.002 和 p<0.0001）。接种疫苗后，除了两名 C2 缺乏症患者的两份血清和一份对照者的血清外，其余血清均显示出足够的 SBA（存活细菌的比例<50%）。接种疫苗前，C2 缺乏症患者的 SBA 与血清中 MBL 浓度呈负相关（具有较高 MBL 浓度的细菌存活率较低；r=-0.55，p=0.008）。接种疫苗后，C2 缺乏症患者的 SBA 与血清 IgG Hib 抗体浓度呈负相关（r=-0.56，p=0.01）。总之，C2D 患者接种疫苗后，自体血清中针对 Hib 的 SBA 增加。在未接种疫苗的 C2 缺乏症患者中，SBA 与 MBL 浓度相关，为 C2D 中存在 MBL 依赖性 C2 旁路机制提供了进一步的支持。
