Agmon-Levin Nancy, Dagan Amir, Peri Yogev, Anaya Juan-Manuel, Selmi Carlo, Tincani Angela, Bizzaro Nicola, Stojanovich Ljudmila, Damoiseaux Jan, Cohen Tervaert Jan Willem, Mosca Marta, Cervera Ricard, Shoenfeld Yehuda
Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center; and Sackler Faculty of Medicine, Tel-Aviv University, Israel.
Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center; and Internal Medicine T, Chaim Sheba Medical Center, Tel Aviv, Israel.
Clin Exp Rheumatol. 2017 Nov-Dec;35(6):929-935. Epub 2017 Jul 6.
The presence of anti-Ro/SSA and anti-La/SSB antibodies has been linked with autoimmunity in general and with several autoimmune diseases (AID) in particular. In the current study we evaluated these antibodies in a wide spectrum of AID as well as the links between them and anti-infectious antibodies.
We examined 2082 sera from patients with 16 different AID compared to 524 sera from geographically-matched healthy controls, for the presence and titres of anti-Ro/SSA and anti-La/SSB. All samples were also tested for a variety of anti-infectious agents' antibodies using the BioPlex 2200-immunoassay (Bio-Rad, USA).
Anti-Ro/SSA was more prevalent, with significantly higher titre in 5 autoimmune diseases namely Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS) both primary and APS linked to SLE, systemic sclerosis (SSc) and primary biliary cirrhosis (PBC). Anti-La/SSB was more prevalent with higher titers in SS, SLE, APS linked to SLE and PBC. Prevalence, but not titers, of both antibodies were higher also in polymyositis (PM). Additionally, we found a correlation between anti-Ro/SSA antibodies and antibodies of the IgM and IgG subtypes directed at cytomegalovirus as well as IgG-antibodies directed at Epstein-Barr virus (EBV) and toxoplasma (p<0.001). Anti-La/SSB antibodies correlated with the presence of IgG antibodies against EBV early antigen (p<0.001).
In a large cohort of patients with autoimmune diseases we found an association between anti-Ro/SSA and anti-La/SSB antibodies and 6 autoimmune diseases, amongst which primary APS and PM. Additionally, we observed linkages between these autoantibodies and anti-infectious antibodies directed at Epstein-Barr virus, toxoplasma and cytomegalovirus. Our findings support the concept of interplay between infectious agents and autoimmunity, such as the plausibility of an infectious agent that trigger the immune system to produce specific antibodies which will later result in a unique group of AID.
抗Ro/SSA和抗La/SSB抗体的存在通常与自身免疫相关,尤其与几种自身免疫性疾病(AID)有关。在本研究中,我们评估了这些抗体在多种AID中的情况,以及它们与抗感染抗体之间的联系。
我们检测了来自16种不同AID患者的2082份血清,并与来自地理位置匹配的524份健康对照血清进行比较,以检测抗Ro/SSA和抗La/SSB的存在及滴度。所有样本还使用BioPlex 2200免疫测定法(美国伯乐公司)检测了多种抗感染因子的抗体。
抗Ro/SSA更为常见,在5种自身免疫性疾病中滴度显著更高,这5种疾病分别是干燥综合征(SS)、系统性红斑狼疮(SLE)、原发性抗磷脂综合征(APS)以及与SLE相关的APS、系统性硬化症(SSc)和原发性胆汁性肝硬化(PBC)。抗La/SSB在SS、SLE、与SLE相关的APS和PBC中更为常见且滴度更高。两种抗体在多发性肌炎(PM)中的患病率也更高,但滴度无差异。此外,我们发现抗Ro/SSA抗体与针对巨细胞病毒的IgM和IgG亚型抗体以及针对爱泼斯坦-巴尔病毒(EBV)和弓形虫的IgG抗体之间存在相关性(p<0.001)。抗La/SSB抗体与针对EBV早期抗原的IgG抗体的存在相关(p<0.001)。
在一大群自身免疫性疾病患者中,我们发现抗Ro/SSA和抗La/SSB抗体与6种自身免疫性疾病有关,其中包括原发性APS和PM。此外,我们观察到这些自身抗体与针对EBV、弓形虫和巨细胞病毒的抗感染抗体之间存在联系。我们的研究结果支持感染因子与自身免疫之间相互作用的概念,例如一种感染因子引发免疫系统产生特定抗体,随后导致一组独特的AID的合理性。