Characterisation and diagnostic model of monogenic lupus

Area of Science:

• Pediatric Immunology
• Genetics
• Rheumatology

Background:

• Monogenic lupus lacks standardized diagnostic criteria due to its rarity and heterogeneity.
• Previous studies have not comprehensively analyzed diverse pathogenic mechanisms in monogenic lupus.

Purpose of the Study:

• To retrospectively summarize clinical characteristics, genotypes, and treatments of pediatric monogenic lupus patients.
• To develop and evaluate distinct diagnostic models based on various pathogenic pathways for monogenic lupus.
• To improve early identification and diagnosis of monogenic lupus in children.

Main Methods:

• Retrospective analysis of 36 pediatric patients with monogenic lupus and 16 different gene mutations.
• Univariate analysis of pathogenic pathways to identify significant risk factors.
• Application of least absolute shrinkage and selection operator (LASSO) and logistic regression for model construction and evaluation.

Main Results:

• Identified specific risk factors for monogenic lupus in male children under 8.46 years with a family history.
• Characterized distinct clinical presentations associated with Type-I-interferon disorders, immune tolerance pathway defects, and other pathways.
• Proposed optimal diagnostic models for different pathogenic pathways, demonstrating good discrimination and calibration.

Conclusions:

• Increased vigilance for monogenic lupus is warranted in specific pediatric populations.
• Pathway-specific diagnostic models can significantly aid in the early and accurate diagnosis of monogenic lupus in children.
• This research provides a framework for improved diagnostic strategies for rare monogenic autoimmune diseases.