Division of Rheumatology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden.
Rheumatology (Oxford). 2021 Mar 2;60(3):1445-1455. doi: 10.1093/rheumatology/keaa611.
Infections have been proposed as an environmental risk factor for autoimmune disease. Responses to microbial antigens may be studied in vivo during vaccination. We therefore followed patients with SLE and controls during split-virion influenza vaccination to quantify antibody responses against viral antigens and associated cellular and proteome parameters.
Blood samples and clinical data were collected from female patients with SLE with no or HCQ and/or low-dose prednisolone treatment (n = 29) and age- and sex-matched healthy controls (n = 17). Vaccine-specific antibody titres were measured by ELISA and IFN-induced gene expression in monocytes by quantitative PCR. Serum proteins were measured by proximity extension assay and disease-associated symptoms were followed by questionnaires.
The vaccine-specific antibody response was significantly higher in patients compared with controls and titres of IgG targeting the viral proteins were higher in patients than controls at both 1 and 3 months after immunization. Clinical disease symptoms and autoantibody titres remained unchanged throughout the study. Notably, a positive pre-vaccination mRNA-based IFN score was associated with a significantly higher vaccine-specific antibody response and with a broader profile of autoantibody specificities. Screening of serum protein biomarkers revealed higher levels of IFN-regulated proteins in patients compared with controls and that levels of such proteins correlated with the vaccine-specific IgG response, with C-C motif chemokine ligand 3 exhibiting the strongest association.
Augmented antibody responses to viral antigens develop in patients with SLE on no or light treatment and associate with markers of type I IFN system activation at the RNA and protein levels.
感染被认为是自身免疫性疾病的环境风险因素。微生物抗原的反应可以在疫苗接种期间进行体内研究。因此，我们在接受季节性流感疫苗接种的 SLE 患者和对照者中进行了随访，以量化针对病毒抗原的抗体反应以及相关的细胞和蛋白质组学参数。
收集无或使用羟氯喹和/或低剂量泼尼松龙治疗的 SLE 女性患者（n=29）和年龄、性别匹配的健康对照者（n=17）的血液样本和临床数据。通过 ELISA 测量疫苗特异性抗体滴度，通过定量 PCR 测量单核细胞中 IFN 诱导的基因表达。通过邻近延伸测定法测量血清蛋白，并通过问卷调查跟踪疾病相关症状。
与对照者相比，患者的疫苗特异性抗体反应明显更高，且在免疫接种后 1 和 3 个月时针对病毒蛋白的 IgG 滴度均高于对照者。整个研究过程中，临床疾病症状和自身抗体滴度保持不变。值得注意的是，阳性的疫苗接种前基于 mRNA 的 IFN 评分与更高的疫苗特异性抗体反应以及更广泛的自身抗体特异性相关。对血清蛋白生物标志物的筛选显示，与对照者相比，患者中 IFN 调节蛋白的水平更高，并且这些蛋白的水平与疫苗特异性 IgG 反应相关，其中 C-C 基序趋化因子配体 3 表现出最强的相关性。
在接受无或低剂量治疗的 SLE 患者中，针对病毒抗原的抗体反应增强，并与 RNA 和蛋白质水平的 I 型 IFN 系统激活的标志物相关。
