Epitope-specific anti-C1Q autoantibodies in systemic Lupus Erythematosus

Objective
In patients with systemic lupus erythematosus (SLE) complement C1q is frequently targeted by autoantibodies (anti-C1q), that correlate best with active renal disease. Anti-C1q bind to largely unknown epitopes on the collagen-like region (CLR) of this highly functional molecule. Here we aimed at exploring the role of epitope-specific anti-C1q in SLE patients.
Methods
First, 22 sera of SLE patients, healthy controls and anti-C1q positive patients without SLE were screened for anti-C1q epitopes by a PEPperMAP® microarray, expressing CLR of C1q derived peptides with one amino acid (AA) shift in different lengths and conformations. Afterwards, samples of 378 SLE patients and 100 healthy blood donors were analyzed for antibodies against the identified epitopes by peptide-based ELISA. Relationships between peptide-specific autoantibodies and SLE disease manifestations were explored by logistic regression models.
Results
The epitope mapping showed increased IgG binding to three peptid...

研究目的：在系统性红斑狼疮（systemic lupus erythematosus, SLE）患者中，补体C1q（complement C1q）常成为自身抗体（autoantibodies）的靶向靶点，此类自身抗体即抗C1q抗体（anti-C1q），其与活动性肾脏病变的相关性最强。抗C1q抗体可结合该高功能分子胶原样区域（collagen-like region, CLR）上绝大多数尚未明确的表位。本研究旨在探讨表位特异性抗C1q抗体在SLE患者中的作用。

研究方法：首先，采用PEPperMAP®微阵列，对22份SLE患者、健康对照以及无SLE的抗C1q抗体阳性患者的血清进行抗C1q表位筛选；该微阵列可表达源自C1q胶原样区域的肽段，且相邻肽段间存在单个氨基酸（amino acid, AA）偏移，涵盖不同长度与构象。随后，采用基于肽段的酶联免疫吸附试验（peptide-based ELISA），对378例SLE患者及100例健康献血者的血清进行针对已鉴定表位的抗体检测。通过逻辑回归模型（logistic regression models），分析肽段特异性自身抗体与SLE疾病表型之间的关联。

研究结果：表位图谱分析显示，IgG与三种肽段的结合水平显著升高……