Objectives: 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.
Methods: 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.
Results: 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).
Conclusions: 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.