Disciplina de Reumatologia, Universidade Federal de São Paulo, Rua Botucatu 740, 3o andar, São Paulo, SP, ZIP: 04023-062, Brazil.
Departamento de Genética e Biologia Evolutiva, Centro de Estudos do Genoma Humano, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP, Brazil.
Adv Rheumatol. 2019 Aug 6;59(1):36. doi: 10.1186/s42358-019-0076-6.
Complement component 4 (C4) gene copy number (GCN) affects the susceptibility to systemic lupus erythematosus (SLE) in different populations, however the possible phenotype significance remains to be determined. This study aimed to associate C4A, C4B and total C4 GCN and SLE, focusing on the clinical phenotype and disease progression.
C4, C4A and C4B GCN were determined by real-time PCR in 427 SLE patients and 301 healthy controls, which underwent a detailed clinical evaluation according to a pre-established protocol.
The risk of developing SLE was 2.62 times higher in subjects with low total C4 GCN (< 4 copies, OR = 2.62, CI = 1.77 to 3.87, p < 0.001) and 3.59 times higher in subjects with low C4A GCN (< 2 copies; OR = 3.59, CI = 2.15 to 5.99, p < 0.001) compared to those subjects with normal or high GCN of total C4 (≥4) and C4A (≥2), respectively. An increased risk was also observed regarding low C4B GCN, albeit to a lesser degree (OR = 1.46, CI = 1.03 to 2.08, p = 0.03). Furthermore, subjects with low C4A GCN had higher permanent disease damage as assessed by the Systemic Lupus International Collaborating Clinics - Damage Index (SLICC-DI; median = 1.5, 95% CI = 1.2-1.9) than patients with normal or high copy number of C4A (median = 1.0, 95% CI = 0.8-1.1; p = 0.004). There was a negative association between low C4A GCN and serositis (p = 0.02) as well as between low C4B GCN and arthritis (p = 0.02).
This study confirms the association between low C4 GCN and SLE susceptibility, and originally demonstrates an association between low C4A GCN and disease severity.
补体成分 4（C4）基因拷贝数（GCN）会影响不同人群系统性红斑狼疮（SLE）的易感性，但可能的表型意义仍有待确定。本研究旨在探讨 C4A、C4B 和总 C4 GCN 与 SLE 的关系，重点关注临床表型和疾病进展。
采用实时 PCR 法检测 427 例 SLE 患者和 301 例健康对照者的 C4、C4A 和 C4B GCN，所有患者均按既定方案进行详细的临床评估。
与总 C4 GCN 正常或高拷贝数（≥4 拷贝）的患者相比，低总 C4 GCN（<4 拷贝）的患者 SLE 发病风险高 2.62 倍（OR=2.62，95%CI=1.77 至 3.87，p<0.001），低 C4A GCN（<2 拷贝）的患者 SLE 发病风险高 3.59 倍（OR=3.59，95%CI=2.15 至 5.99，p<0.001）。低 C4B GCN 患者的发病风险也有所增加（OR=1.46，95%CI=1.03 至 2.08，p=0.03），但程度较轻。此外，低 C4A GCN 患者的系统红斑狼疮国际合作临床损害指数（SLICC-DI）评分较高（中位数=1.5，95%CI=1.2 至 1.9），高于 C4A 正常或高拷贝数的患者（中位数=1.0，95%CI=0.8 至 1.1；p=0.004）。低 C4A GCN 与浆膜炎（p=0.02）及低 C4B GCN 与关节炎（p=0.02）呈负相关。
本研究证实了低 C4 GCN 与 SLE 易感性之间的关联，且首次证明了低 C4A GCN 与疾病严重程度之间的关联。
