克隆性造血不定潜能与系统性红斑狼疮心血管事件（HEMATOPLUS 研究）
Clonal haematopoiesis of indeterminate potential and cardiovascular events in systemic lupus erythematosus (HEMATOPLUS study).
机构信息
Département de Médecine Interne, Hôpital Bichat, Assistance Publique Hôpitaux de Paris (APHP), Institut National de la Santé et de la Recherche Médicale (INSERM) U1149, Université de Paris, Paris.
Département de Biologie, University of Lille, CNRS, Inserm, CHU Lille, Institut de Recherche contre le Cancer de Lille, UMR9020-UMR-S 1277-Canther-Cancer Heterogeneity, Plasticity and Resistance to Therapies, Lille.
出版信息
Rheumatology (Oxford). 2022 Nov 2;61(11):4355-4363. doi: 10.1093/rheumatology/keac108.
OBJECTIVE
The detection of somatic mutations among the genes of myeloid cells in asymptomatic patients-defining clonal haematopoiesis of indeterminate potential (CHIP)-is associated with a predisposition to cardiovascular events (CVEs) in the general population. We aimed to determine whether CHIP was associated with CVEs in SLE patients.
METHODS
The study is an ancillary study of the randomized, double-blind, placebo-controlled, multicentre PLUS trial conducted from June 2007 through August 2010 at 37 centres in France, involving 573 SLE patients. The search for somatic mutations by high-throughput sequencing of 53 genes involved in clonal haematopoiesis was performed on genomic DNA collected at PLUS inclusion. CHIP prevalence was assessed in SLE and in a retrospective cohort of 479 patients free of haematological malignancy. The primary outcome was an incident CVE in SLE.
RESULTS
Screening for CHIP was performed in 438 SLE patients [38 (29-47) years, 91.8% female]. Overall, 63 somatic mutations were identified in 47 patients, defining a CHIP prevalence of 10.7% in SLE. Most SLE patients (78.7%) carried a single mutation. Most variants (62.5%) were located in the DNMT3A gene. CHIP frequency was related to age and to age at SLE diagnosis, and was associated with a lower frequency of aPLs. CHIP occurred >20 years earlier (P < 0.00001) in SLE than in controls. The detection of CHIP at inclusion was not found to be associated with occurrence of CVEs during follow-up [HR = 0.42 (0.06-3.21), P = 0.406].
CONCLUSION
The prevalence of CHIP is relatively high in SLE for a given age, but was not found to be associated with incident CVEs.
TRIAL REGISTRATION
ClinicalTrials.gov, https://clinicaltrials.gov, NCT05146414.
目的
在无症状患者中检测髓系细胞基因的体细胞突变——定义为不确定潜能的克隆性造血（CHIP）——与普通人群中的心血管事件（CVE）易感性相关。我们旨在确定 CHIP 是否与 SLE 患者的 CVE 相关。
方法
该研究是 2007 年 6 月至 2010 年 8 月在法国 37 个中心进行的、多中心、随机、双盲、安慰剂对照 PLUS 试验的辅助研究，涉及 573 例 SLE 患者。通过高通量测序对 53 个与克隆性造血相关的基因进行基因组 DNA 检测，以寻找体细胞突变。在 PLUS 纳入时采集基因组 DNA，评估 SLE 患者和 479 例无血液恶性肿瘤的回顾性队列中 CHIP 的患病率。主要结局是 SLE 患者的新发 CVE。
结果
对 438 例 SLE 患者（38[29-47]岁，91.8%为女性）进行了 CHIP 筛查。总体而言，47 例患者中有 63 个体细胞突变，定义了 SLE 中 10.7%的 CHIP 患病率。大多数 SLE 患者（78.7%）携带单个突变。大多数变异（62.5%）位于 DNMT3A 基因。CHIP 频率与年龄和 SLE 发病年龄相关，与 aPLs 的频率较低相关。与对照组相比，SLE 中 CHIP 的检测早发生了 >20 年（P < 0.00001）。在随访期间，CHIP 的检测结果与 CVE 的发生无关[HR=0.42（0.06-3.21），P=0.406]。
结论
对于给定年龄，SLE 中 CHIP 的患病率相对较高，但与新发 CVE 无关。
试验注册
ClinicalTrials.gov，https://clinicaltrials.gov，NCT05146414。
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