Stone M A, Payne U, Schentag C, Rahman P, Pacheco-Tena C, Inman R D
Toronto Western Research Institute, University Health Network, Newfoundland, Canada.
Rheumatology (Oxford). 2004 Feb;43(2):148-55. doi: 10.1093/rheumatology/keg482. Epub 2003 Aug 29.
Using humoral immune responses, Klebsiella pneumoniae has been implicated as a candidate microbial trigger in ankylosing spondylitis (AS) by several investigators but refuted by others. The objective of this case-control study was to compare the cellular (T-cell proliferation) and humoral (IgG and IgA, by ELISA) immune responses of affected individuals in multiplex AS families with those of unaffected family members and normal healthy controls in order to find out whether affected individuals exhibit a predominant immune response to K. pneumoniae.
Twenty-five families with two or more individuals affected with AS and 34 normal healthy controls matched with the affected family members for age, sex and ethnicity were enrolled in the study. All affected (n = 57) and unaffected (n = 37) family members had a detailed clinical evaluation. Peripheral blood was drawn to determine T-lymphocyte proliferation and the IgG and IgA (by ELISA analysis) immune responses to K. pneumoniae, Salmonella typhimurium, Yersinia enterocolitica and Chlamydia trachomatis. Immune responses to each of the four candidate organisms were compared in affected and unaffected individuals. Each individual was classified by the predominant antigenic immune response that they showed when comparison was made among the same concentrations of the four candidate microbial antigens. This stratification was then used (i) to compare immune responses in affected and unaffected family members and (ii) to compare clinical characteristics of affected family members.
There was no difference in mean stimulation indices or antibody responses between affected and unaffected family members for each of the candidate organisms. In terms of predominant cellular immune responses to these organisms, there was no difference between affected and unaffected family members with respect to K. pneumoniae, C. trachomatis or Y. enterocolitica. However, a higher percentage of affected family members (25.9%) exhibited a predominant response to S. typhimurium compared with unaffected family members (5.9%, P < 0.02). In assessing antibody titres, K. pneumoniae was the predominant amongst these four organisms, but there was no difference between affected family members, unaffected family members and normal healthy controls. There was no relationship between immune responses and clinical characteristics.
Our analysis of affected and unaffected family members in familial AS demonstrated no significant differences with respect to cellular or humoral immune responses to K. pneumoniae and three control microbes. In addition, K. pneumoniae did not exhibit a predominant immune response in affected individuals. Thus we find no supportive evidence to implicate a causal role for K. pneumoniae in familial AS.
通过体液免疫反应，一些研究人员认为肺炎克雷伯菌是强直性脊柱炎（AS）的候选微生物触发因素，但另一些人则予以反驳。本病例对照研究的目的是比较AS多重家庭中患病个体与未患病家庭成员及正常健康对照者的细胞免疫反应（T细胞增殖）和体液免疫反应（通过ELISA检测IgG和IgA），以确定患病个体是否对肺炎克雷伯菌表现出主要免疫反应。
招募了25个有两名或更多AS患者的家庭以及34名年龄、性别和种族与患病家庭成员相匹配的正常健康对照者参与研究。所有患病（n = 57）和未患病（n = 37）家庭成员均进行了详细的临床评估。采集外周血以测定T淋巴细胞增殖以及对肺炎克雷伯菌、鼠伤寒沙门菌、小肠结肠炎耶尔森菌和沙眼衣原体的IgG和IgA免疫反应（通过ELISA分析）。比较患病和未患病个体对这四种候选微生物的免疫反应。在相同浓度的四种候选微生物抗原之间进行比较时，根据个体表现出的主要抗原免疫反应对每个个体进行分类。然后利用这种分层方法：（i）比较患病和未患病家庭成员的免疫反应；（ii）比较患病家庭成员的临床特征。
对于每种候选微生物，患病和未患病家庭成员的平均刺激指数或抗体反应均无差异。就对这些微生物的主要细胞免疫反应而言，患病和未患病家庭成员在对肺炎克雷伯菌、沙眼衣原体或小肠结肠炎耶尔森菌的反应方面没有差异。然而，与未患病家庭成员（5.9%，P < 0.02）相比，更高比例的患病家庭成员（25.9%）对鼠伤寒沙门菌表现出主要反应。在评估抗体滴度时，肺炎克雷伯菌是这四种微生物中最主要的，但患病家庭成员、未患病家庭成员和正常健康对照者之间没有差异。免疫反应与临床特征之间没有关联。
我们对家族性AS中患病和未患病家庭成员的分析表明，在对肺炎克雷伯菌和三种对照微生物的细胞免疫或体液免疫反应方面没有显著差异。此外，肺炎克雷伯菌在患病个体中并未表现出主要免疫反应。因此，我们没有找到支持肺炎克雷伯菌在家族性AS中起因果作用的证据。
