Department of Rheumatology, Children's Hospital of Fudan University, Shanghai, China.
Medical Transformation Centre, Children's Hospital of Fudan University, Shanghai, China.
Clin Exp Rheumatol. 2021 Jan-Feb;39(1):214-222. doi: 10.55563/clinexprheumatol/zte897. Epub 2020 Dec 4.
Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with extreme clinical heterogeneity and significant differences between populations. Here, we performed whole exome sequencing (WES) in 52 children with SLE from China.
The patients all fulfilled the 2012 SLICC criteria for the classification of SLE. Patients were enrolled if they met one of the following criteria: 1. age of disease onset under 5 years; 2. family history of autoimmune disease; 3. syndromic SLE; and 4. complicated conditions, such as life-threatening and refractory SLE.
52 out of 281 newly diagnosed pSLE patients met the inclusion criteria. We identified causative mutations in 12 patients in five different genes: SLC7A7, NRAS, TNFAIP3, PIK3CD, and IDS. The age of onset was under five years in eight patients (8/15, p=0.003) with mutations. Two of 5 patients had a family history of autoimmune disease, with family members developing different autoimmune diseases. Causal mutations were identified in five patients who presented with syndromic SLE (5/5 p=0.000) and in another five patients who presented with primary immunodeficiency diseases (5/5, p=0.000). Causal mutations were detected in 12 of 36 patients with SLEDAI scores>14 (12/36, p=0.023) and in 9 of 17 patients with haematological and renal involvement (9/17, p=0.048).
We revealed a significant fraction of monogenic SLE aetiologies using WES (12/52, 23.1%). WES should perform in patients with very early onset SLE (<5 years of age), syndromic SLE, severe SLE (SLEDAI score>14), family history of autoimmune disease, primary immunodeficiency disease and renal and haematological involvement.
系统性红斑狼疮（SLE）是一种具有极端临床异质性和人群间显著差异的自身免疫性疾病原型。在此，我们对 52 例来自中国的 SLE 儿童进行了全外显子组测序（WES）。
所有患者均符合 2012 年 SLICC 用于 SLE 分类的标准。如果患者符合以下标准之一，则将其纳入研究：1. 发病年龄<5 岁；2. 自身免疫性疾病家族史；3. 综合征性 SLE；4. 复杂情况，如危及生命和难治性 SLE。
281 例新诊断的 pSLE 患者中有 52 例符合纳入标准。我们在五个不同基因（SLC7A7、NRAS、TNFAIP3、PIK3CD 和 IDS）的 12 名患者中发现了致病突变。在发病年龄<5 岁的 8 名患者（8/15，p=0.003）中发现了突变。5 名有自身免疫性疾病家族史的患者中，有 2 名患者的家族成员患有不同的自身免疫性疾病。5 例综合征性 SLE 患者（5/5，p=0.000）和 5 例原发性免疫缺陷病患者（5/5，p=0.000）中发现了致病突变。在 SLEDAI 评分>14 的 36 例患者中有 12 例（12/36，p=0.023）和在有血液学和肾脏受累的 17 例患者中有 9 例（9/17，p=0.048）中发现了致病突变。
我们使用 WES 发现了显著比例的单基因 SLE 病因（12/52，23.1%）。WES 应该在发病年龄<5 岁、综合征性 SLE、严重 SLE（SLEDAI 评分>14）、自身免疫性疾病家族史、原发性免疫缺陷病和肾脏及血液学受累的患者中进行。
