Uomori Kaori, Nozawa Kazuhisa, Ikeda Keigo, Doe Kentaro, Yamada Yusuke, Yamaguchi Ayako, Fujishiro Maki, Kawasaki Mikiko, Morimoto Shinji, Takamori Kenji, Sekigawa Iwao, Chan Edward K L, Takasaki Yoshinari
a Department of Internal Medicine and Rheumatology , Faculty of Medicine, Juntendo University , Tokyo , Japan .
b Juntendo University Urayasu Hospital, Juntendo University Graduate School of Medicine , Urayasu , Japan , and.
Autoimmunity. 2016 Aug;49(5):347-56. doi: 10.1080/08916934.2016.1196676. Epub 2016 Jun 21.
Novel autoantibodies against nuclear antigen of 14 kDa (NA-14)/Sjögren's syndrome nuclear antigen-1 (SSNA-1) are predominantly recognized in sera of patients with primary Sjögren's syndrome (pSS). However, the detailed characteristics of the anti-NA-14 antibody remain unknown. Here, we sought to clarify the characteristics of anti-SSNA-1/NA-14 antibodies and the mechanisms of autoantibody production using sera from patients with connective tissue diseases (including pSS), autoimmune sera reacting with standard autoantigens (SS-A/Ro and/or SS-B/La, ds DNA, Scl-70 and Jo-1), and normal healthy controls (NHCs). Anti-NA-14 antibodies were predominantly recognized in sera from patients with pSS and in autoimmune sera reacting with thSS-A/Ro and/or -SS-B/Lo. Indirect immunofluorescence analysis showed that NA-14 was strongly expressed in mitotic-phase cells. Patients with pSS having anti-NA-14 antibodies exhibited significant elevation of serum IP-10 and BAFF compared to that in patients with pSS without anti-NA-14 antibodies and NHCs. Thus, our data demonstrated that anti-NA-14 antibodies could be classified as novel autoantibodies reacting with mitosis-related autoantigens predominantly recognized in pSS. Moreover, interferon-γ played an important role in the production of anti-NA-14 autoantibodies as patients with pSS having anti-NA-14 antibodies exhibited increased serum levels of IP-10 and BAFF.
针对14 kDa核抗原(NA-14)/干燥综合征核抗原-1(SSNA-1)的新型自身抗体主要在原发性干燥综合征(pSS)患者血清中被识别。然而,抗NA-14抗体的详细特征仍不清楚。在此,我们试图利用结缔组织病患者(包括pSS)的血清、与标准自身抗原(SS-A/Ro和/或SS-B/La、双链DNA、Scl-70和Jo-1)反应的自身免疫血清以及正常健康对照(NHC)来阐明抗SSNA-1/NA-14抗体的特征和自身抗体产生的机制。抗NA-14抗体主要在pSS患者血清以及与SS-A/Ro和/或-SS-B/Lo反应的自身免疫血清中被识别。间接免疫荧光分析显示,NA-14在有丝分裂期细胞中强烈表达。与无抗NA-14抗体的pSS患者和NHC相比,有抗NA-14抗体的pSS患者血清中IP-10和BAFF显著升高。因此,我们的数据表明,抗NA-14抗体可被归类为与主要在pSS中识别的有丝分裂相关自身抗原反应的新型自身抗体。此外,干扰素-γ在抗NA-14自身抗体的产生中起重要作用,因为有抗NA-14抗体的pSS患者血清中IP-10和BAFF水平升高。