Monogenic lupus: insights into disease pathogenesis and therapeutic opportunities.

Curr Opin Rheumatol

China-Australia Centre for Personalized Immunology (CACPI), Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China.

Published: May 2024

Purpose Of Review: This review aims to provide an overview of the genes and molecular pathways involved in monogenic lupus, the implications for genome diagnosis, and the potential therapies targeting these molecular mechanisms.

Recent Findings: To date, more than 30 genes have been identified as contributors to monogenic lupus. These genes are primarily related to complement deficiency, activation of the type I interferon (IFN) pathway, disruption of B-cell and T-cell tolerance and metabolic pathways, which reveal the multifaceted nature of systemic lupus erythematosus (SLE) pathogenesis.

Summary: In-depth study of the causes of monogenic lupus can provide valuable insights into of pathogenic mechanisms of SLE, facilitate the identification of effective biomarkers, and aid in developing therapeutic strategies.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7616038PMC
http://dx.doi.org/10.1097/BOR.0000000000001008DOI Listing

Publication Analysis

Top Keywords

monogenic lupus
16
monogenic
4
lupus insights
4
insights disease
4
disease pathogenesis
4
pathogenesis therapeutic
4
therapeutic opportunities
4
opportunities purpose
4
purpose review
4
review review
4

Similar Publications

Anifrolumab in Monogenic Lupus caused by TREX1 Mutation.

J Clin Immunol

December 2024

Division of Rheumatology, and the Unit of Medical Genetics, Laboratory of Cytogenetics and Molecular Genetics, Institute for Research and Health Care (IRCCS), Ospedale Pediatrico Bambino Gesù, Rome, Italy.

View Article and Find Full Text PDF

Systemic lupus erythematosus (SLE) is an autoimmune disease whose pathophysiology remains incompletely understood, involving genetic and epigenetic factors. However, an increasing small subset of patients present with monogenic lupus, providing insight into the pathogenesis of the disease. This systematic review focuses on SLE associated with A20 haploinsufficiency (HA20), a monogenic disorder associated with tumor necrosis factor alpha-induced protein 3 gene (TNFAIP3) variants.

View Article and Find Full Text PDF

A deep dive into monogenic lupus: insights on DNASE1L3 mutation.

Rheumatology (Oxford)

December 2024

Department of Child Health, Royal Hospital, Ministry of Health, Muscat, Sultanate of Oman.

Objective: In this study, we aim to describe the largest cohort of monogenic lupus caused by DNASE1L3 yet reported, describing its phenotypic characteristics and outcomes.

Methods: We performed a multicentre retrospective chart review for enrolled patients with childhood-onset systemic lupus erythematosus (cSLE) followed in pediatric rheumatology tertiary centers in the Sultanate of Oman. We included cSLE patients with genetically confirmed DNASE1L3 mutation.

View Article and Find Full Text PDF

Emerging concepts and treatments in autoinflammatory interferonopathies and monogenic systemic lupus erythematosus.

Nat Rev Rheumatol

January 2025

Translational Autoinflammatory Diseases Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Over the past two decades, the number of genetically defined autoinflammatory interferonopathies has steadily increased. Aicardi-Goutières syndrome and proteasome-associated autoinflammatory syndromes (PRAAS, also known as CANDLE) are caused by genetic defects that impair homeostatic intracellular nucleic acid and protein processing respectively. Research into these genetic defects revealed intracellular sensors that activate type I interferon production.

View Article and Find Full Text PDF

Background: Spondyloenchondrodysplasia is classified as an interferonopathy resulting from recessive mutations in the gene and manifests with various clinical features, including distinctive skeletal dysplasia, neurological abnormalities, immune dysfunction resembling systemic lupus erythematosus (SLE) and Sjogren's syndrome. While SLE is typically considered multifactorial and more prevalent in adulthood, a subset of approximately 10%-25% of childhood cases arise from monogenic form. Among these, spondyloenchondrodysplasia accounts for only a rare fraction of monogenic lupus cases, with only 22 reported instances in the literature.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!