Characterisation and diagnostic model of monogenic lupus

Abstract

Standardised diagnostic criteria for monogenic lupus are lacking owing to its rarity, diverse phenotypes, and significant heterogeneity in pathogenesis, phenotypic characteristics, disease course, and outcomes. Further, no studies have analysed the characteristics of multiple pathological mechanisms of monogenic lupus. Therefore, we retrospectively summarised the clinical characteristics, genotypes, and treatment of 36 patients with monogenic lupus with 16 different gene mutations admitted to the Department of Immunology at Beijing Children's Hospital between June 2021 and July 2024. Children with classic lupus were randomly allocated to the control group. A univariate analysis was conducted on different pathogenic pathways to identify relevant significant risk factors. The least absolute shrinkage and selection operator and logistic regression were applied to construct multiple models. The discrimination and calibration abilities of these models were then evaluated, and the optimal diagnostic model for each pathway was proposed. We found that increased vigilance for monogenic lupus is necessary for male children with an onset age of < 8.46 years and a family history. Type-I-interferon disorders should be considered in patients with growth retardation, interstitial lung disease, intracranial calcifications, characteristic rashes, splenomegaly, and elevated liver enzymes. Monogenic lupus involving immune tolerance pathways should be considered in patients with repeated infections, lymphoproliferation, or elevated double-negative T-lymphocyte proportion. Monogenic lupus caused by another pathway should be considered in patients with abdominal symptoms, oral ulcers, and elevated C-reactive protein levels. Overall, our study proposes distinct diagnostic models based on various pathogenic pathways, aiding in early identification and diagnosis of monogenic lupus in children.

Keywords: Clinical characteristics; Diagnostic model; Monogenic lupus; Pathogenic pathways.