Department of Genetics, Istanbul Faculty of Medicine, Istanbul Istanbul University, Istanbul, Turkey.
Clin Exp Rheumatol. 2009 Mar-Apr;27(2 Suppl 53):S67-72.
Behçet's disease (BD) is a multisystem inflammatory disorder characterized by recurrent oral ulcers, genital ulcers and ocular inflammation, as well as skin, joint, vascular, pulmonary, central nervous system (CNS) and gastrointestinal tract manifestations. The etiopathogenesis of BD has not yet been identified; but it has generally been accepted that several environmental factors may induce an inflammatory attack in genetically susceptible individuals. In this study, we aimed to identify antigens that could elicit high-titer IgG responses by the serological analysis of recombinant expression of cDNA libraries method (SEREX).
We screened a human testis cDNA library with pooled sera obtained from 4 BD patients by SEREX. Antigens that were identified with the initial analysis were selected for seroreactivity analysis of a larger group of BD patients (n=78) and controls (n=66) by serological immunoscreening.
We observed seroreactivity against 6 antigens using the pooled sera. These included rabaptin 5 (RABPT5), PTEN-induced putative kinase 1 (PINK1), switch associated protein 70 (SWAP70), interferon-induced protein with tetratricopeptide repeats 2 (IFIT2), ankyrin repeat domain 20 family, member A1 (ANKRD20A1), and an unknown antigen. Eleven out of 82 (13.4%) BD patients were found to have antibodies elicited against PINK1 antigen, when none of the control sera showed reactivity (p=0.001). There was no significant difference in the frequency of other defined antigens between the patient and control groups. However, among BD clinical sub-groups, anti-SWAP70 antibodies were found to associate with vascular involvement.
In this study, antibodies against PINK1 were found to specifically associate with BD while SWAP70 antibody was associated with clinical sub-groups of BD. Although variations in both genetic background and environmental factors may affect the outcome of serological responses, our results suggest that serological screening can be used to identify antigens that elicit antibody responses associated with BD.
白塞病(BD)是一种多系统炎症性疾病,其特征是复发性口腔溃疡、生殖器溃疡和眼部炎症,以及皮肤、关节、血管、肺部、中枢神经系统(CNS)和胃肠道表现。BD 的病因尚未确定;但人们普遍认为,一些环境因素可能在遗传易感个体中引发炎症攻击。在这项研究中,我们旨在通过 cDNA 文库的血清学分析方法(SEREX)鉴定可引起高滴度 IgG 反应的抗原。
我们通过 SEREX 用来自 4 名 BD 患者的混合血清筛选人睾丸 cDNA 文库。通过初步分析鉴定的抗原被选择用于通过血清学免疫筛选对更大的 BD 患者组(n=78)和对照组(n=66)进行血清反应性分析。
我们使用混合血清观察到针对 6 种抗原的血清反应性。这些包括 rabaptin 5(RABPT5)、PTEN 诱导的假定激酶 1(PINK1)、交换相关蛋白 70(SWAP70)、干扰素诱导的四肽重复蛋白 2(IFIT2)、ankyrin 重复结构域 20 家族成员 A1(ANKRD20A1)和未知抗原。在 82 名 BD 患者中,有 11 名患者被发现对 PINK1 抗原产生抗体,而对照组血清均无反应(p=0.001)。患者和对照组之间其他定义抗原的频率没有显著差异。然而,在 BD 临床亚组中,抗 SWAP70 抗体与血管受累有关。
在这项研究中,发现针对 PINK1 的抗体与 BD 特异性相关,而 SWAP70 抗体与 BD 的临床亚组相关。尽管遗传背景和环境因素的差异可能会影响血清反应的结果,但我们的结果表明,血清学筛选可用于鉴定与 BD 相关的抗体反应抗原。