High prevalence of subclass-specific binding and neutralizing antibodies against Clostridium difficile toxins in adult cystic fibrosis sera: possible mode of immunoprotection against symptomatic C. difficile infection.
High prevalence of subclass-specific binding and neutralizing antibodies against Clostridium difficile toxins in adult cystic fibrosis sera: possible mode of immunoprotection against symptomatic C. difficile infection.
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DOI：
10.2147/ceg.s133939
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发表时间：
2017
影响因子：
2.4
通讯作者：
Wilcox MH
中科院分区：
文献类型：
--
作者：
Monaghan TM;Negm OH;MacKenzie B;Hamed MR;Shone CC;Humphreys DP;Acharya KR;Wilcox MH
尽管有多种危险因素和艰难梭菌的高定殖率，但艰难梭菌的发生率仍然很高。在囊性纤维化患者中艰难梭菌感染是罕见的。本研究的目的是比较结合C的患病率。在患有囊性纤维化、有症状的C.艰难梭菌感染（无囊性纤维化）和健康对照。对高度纯化的全C.艰难梭菌毒素A和B（毒素型0，菌株VPI 10463，核糖体型087），来自C.用蛋白质芯片技术检测艰难梭菌毒素B片段的表达菌株CCUG 20309和二元毒素B片段的前体形式pCDTb。中和C.艰难梭菌毒素A和B使用基于Caco-2细胞的中和试验进行评价。与健康对照组（n=17）和有症状的C型患者相比，成人囊性纤维化患者（n=16）血清伊加抗毒素A和B水平以及抗毒素A的中和抗体显著更高。艰难梭菌感染（n=16）; p≤0.05。IgG的反应模式相同，除了组间抗毒素A IgG水平无差异。与健康对照组（毒素A和B）和C.艰难梭菌感染（毒素A）时，来自囊性纤维化患者的血清显示出显著更强的保护性抗毒素中和抗体应答。对C.在囊性纤维化人群中，艰难梭菌毒素可能对症状性C.艰难感染这种保护可能会失去在移植后的设置，其中血清监测抗C。艰难梭菌毒素抗体滴度可能具有临床价值。
Despite multiple risk factors and a high rate of colonization for Clostridium difficile, the occurrence of C. difficile infection in patients with cystic fibrosis is rare. The aim of this study was to compare the prevalence of binding C. difficile toxin-specific immunoglobulin (Ig)A, IgG and anti-toxin neutralizing antibodies in the sera of adults with cystic fibrosis, symptomatic C. difficile infection (without cystic fibrosis) and healthy controls. Subclass-specific IgA and IgG responses to highly purified whole C. difficile toxins A and B (toxinotype 0, strain VPI 10463, ribotype 087), toxin B from a C. difficile toxin-B-only expressing strain (CCUG 20309) and precursor form of B fragment of binary toxin, pCDTb, were determined by protein microarray. Neutralizing antibodies to C. difficile toxins A and B were evaluated using a Caco-2 cell-based neutralization assay. Serum IgA anti-toxin A and B levels and neutralizing antibodies against toxin A were significantly higher in adult cystic fibrosis patients (n=16) compared with healthy controls (n=17) and patients with symptomatic C. difficile infection (n=16); p≤0.05. The same pattern of response prevailed for IgG, except that there was no difference in anti-toxin A IgG levels between the groups. Compared with healthy controls (toxins A and B) and patients with C. difficile infection (toxin A), sera from cystic fibrosis patients exhibited significantly stronger protective anti-toxin neutralizing antibody responses. A superior ability to generate robust humoral immunity to C. difficile toxins in the cystic fibrosis population is likely to confer protection against symptomatic C. difficile infection. This protection may be lost in the post-transplantation setting, where sera monitoring of anti-C. difficile toxin antibody titers may be of clinical value.