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.
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http://dx.doi.org/10.1097/BOR.0000000000001008 | DOI Listing |
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.
Autoimmun Rev
December 2024
Department of Clinical Immunology and Internal Medicine, CHU of Caen Normandie, 14000 Caen, France; Normandie Univ, UNICAEN, CHU de Caen Normandie, 14000 Caen, France.
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 PDFRheumatology (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.
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 PDFLupus
January 2025
Division of Rheumatology, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey.
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.
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