Genetic heterogeneity in Chinese children with systemic lupus erythematosus

Objective 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, TNIAIP3, 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 autoinunune 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). Conclusion We revealed a significant fraction of inonogenic 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 autointmune disease, primary immunodeficiency disease and renal and haematological involvement.