Does the esv3587290 Copy-Number Variation in the <em>VANGL1 </em>Gene Differ as a Genetic Factor for Developing Nephritis in Mexican Childhood-Onset Systemic Lupus Erythematosus Patients? DOI Open Access
Miguel Ángel Alcántara-Ortigoza, Ana Luisa Rodríguez‐Lozano, Bernardette Estandía‐Ortega

et al.

Published: June 5, 2024

A ~3-kb deletion-type DNA copy-number variation (CNV, esv3587290) located at intron 7 of the VANGL1 gene (1p13.1, MIM*610132) has been proposed as a genetic factor for developing lupus nephritis (LN) in adult systemic erythematosus (SLE) patients across European-descent populations, but its replication other ethnicities inconsistent and association with LN childhood-onset SLE (cSLE) remains unknown. Here, we performed an exploratory study sample 66 unrelated cSLE Mexican (11 males, 55 females; ages 7.8 to 18.6 years). Two stratified groups were compared: (N=39) or without (N=27) LN, diagnosed by renal biopsy (N=17), proteinuria (N=33), urinary protein:creatinine ratio &gt;0.2 (N=34), erythrocyturia and/or granular casts sediment (N=16). For esv3587290 CNV genotyping, end-point PCR assay breakpoint confirmation Sanger sequencing. We also determined allelic frequencies 181 deidentified ethnically-matched individuals (reference group). The obtained genotypes tested Hardy-Weinberg equilibrium (HWE) c2 test. Associations between calculating Odds Ratio (OR) using Pearson's tests 95% confidence interval P&le;0.05. allele (OR 0.108, CI 0.034-0.33, P=0.00003) heterozygous genotype 0.04, 0.119-0.9811, P=0.002) showed significant protective effect against development. Finally, characterized precise NG_016548.1(NM_138959.3):c.1314+1339_1315-897del (https://databases.lovd.nl/shared/variants/0000918418#00025811) our population. This report supports notion that broad heterogeneity underlies susceptibility LN.

Language: Английский

Animal models of lupus nephritis: the past, present and a future outlook DOI Creative Commons
Divya S. Katikaneni, Laurence Morel, Yogesh Scindia

et al.

Autoimmunity, Journal Year: 2024, Volume and Issue: 57(1)

Published: March 13, 2024

Lupus nephritis (LN) is the most severe end-organ pathology in Systemic Erythematosus (SLE). Research has enhanced our understanding of immune effectors and inflammatory pathways LN. However, even with best available therapy, rate complete remission for proliferative LN remains below 50%. A deeper resistance or susceptibility renal cells to injury during progression SLE critical identifying new targets developing effective long-term therapies. The complex heterogeneous nature LN, combined limitations clinical research, make it challenging investigate aetiology this disease directly patients. Hence, multiple murine models resembling SLE-driven are utilised dissect LN's cellular genetic mechanisms, identify therapeutic targets, screen novel compounds. This review discusses commonly used spontaneous inducible mouse that have provided insights into pathogenic mechanisms maintenance therapies

Language: Английский

Citations

6
The role of DNA in the pathogenesis of SLE: DNA as a molecular chameleon DOI
David S. Pisetsky, Alan Herbert

Annals of the Rheumatic Diseases, Journal Year: 2024, Volume and Issue: 83(7), P. 830 - 837

Published: May 15, 2024

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterised by antibodies to DNA (anti-DNA) and other nuclear macromolecules. Anti-DNA are markers for classification activity promote pathogenesis forming immune complexes that deposit in the tissue or stimulate cytokine production. Studies on antibody response have focused primarily conformation of known as B-DNA, classic right-handed double helix. Among conformations DNA, Z-DNA left-handed helix with zig-zag backbone; hence, term Z-DNA. formation favoured certain base sequences, energetically unfavourable flip from B-DNA dependent conditions. differs its immunogenicity animal models. Furthermore, anti-Z-DNA antibodies, but not anti-B-DNA can be present otherwise healthy individuals. In SLE, occur association cross-reactive response, rising falling together. While formed transiently chromosomal stably bacterial biofilms; biofilms provide protection against antibiotics challenges including elements host defence. The high GC content also favours do DNA-binding proteins origin. Together, these findings suggest sources enhance and, production bind both As such, act molecular chameleon that, when stabilised conformation, drive autoimmunity.

Language: Английский

Citations

6
Early-onset lupus nephritis DOI Creative Commons
Francesco Peyronel, Giovanni Maria Rossi,

Giulia Palazzini

et al.

Clinical Kidney Journal, Journal Year: 2024, Volume and Issue: 17(8)

Published: July 13, 2024

ABSTRACT Early-onset systemic lupus erythematous (SLE) is a distinct clinical entity characterized by the onset of disease manifestations during childhood. Despite some similarities to patients who are diagnosed adulthood, early-onset SLE typically displays greater severity, with aggressive multiorgan involvement, lower responsiveness classical therapies, and more frequent flares. Lupus nephritis one most severe complications represents major risk factor for long-term morbidity mortality, especially in children. This review focuses on histological aspects nephritis, aiming at highlighting relevant differences adult patients, emphasizing outcomes discussing management complications. We also discuss monogenic lupus, spectrum conditions caused single gene variants affecting complement cascade, extracellular intracellular nucleic acid sensing processing, occasionally other metabolic pathways. These forms develop early life often have that resemble sporadic SLE, whereas their response standard treatments poor.

Language: Английский

Citations

4
Age-Associated B Cells in Autoimmune Diseases: Pathogenesis and Clinical Implications DOI Creative Commons
Guangyang Xie, Xiaojing Chen, Yanli Gao

et al.

Clinical Reviews in Allergy & Immunology, Journal Year: 2025, Volume and Issue: 68(1)

Published: Feb. 17, 2025

Abstract As a heterogeneous B cell subset, age-associated cells (ABCs) exhibit distinct transcription profiles, extrafollicular differentiation processes, and multiple functions in autoimmunity. TLR7 TLR9 signals, along with IFN-γ IL-21 stimulation, are both essential for ABC differentiation, which is also regulated by chemokine receptors including CXCR3 CCR2 integrins CD11b CD11c. Given their antigen uptake presentation, autoantibody proinflammatory cytokine secretion, T helper activation, ABCs display potential the prognosis, diagnosis, therapy autoimmune diseases, systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, sclerosis, neuromyelitis optica spectrum disorders, ankylosing spondylitis. Specifically targeting inhibiting T-bet CD11c activating ARA2 represents therapeutic strategies SLE RA. Although single-cell sequencing technologies have recently revealed characteristics of ABCs, further investigations to explore validate ABC-target therapies still warranted.

Language: Английский

Citations

0
Solute carrier family 15 member 4, an emerging therapeutic target for systemic lupus erythematosus DOI
Lai Wang, Jiao Jiang, Haoyuan Yin

et al.

International Reviews of Immunology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 15

Published: April 21, 2025

Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by excessive production of type I interferons (IFNs) and autoantibodies with limited effective clinical treatments. Solute carrier family 15 member 4 (SLC15A4), proton-coupled oligopeptide transporter, facilitates the transmembrane transport L-histidine some di- tripeptides from lysosome to cytosol. A growing body evidence has elucidated critical role SLC15A4 in pathogenesis progression SLE. Genome-wide association studies have identified as new susceptibility locus Further mechanistical demonstrated that involves IFNs plasmacytoid dendritic cells (pDCs) its necessity B for autoantibody models. These strongly support potential promising therapeutic target This review aims summarize recent advances understanding SLE development SLC15A4-targeted inhibitors well discuss treatment.

Language: Английский

Citations

0
Autoimmune Diseases Arising Out of Single Gene Defects DOI

Emily K. Thomas,

David Thomas

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Monogenic lupus: insights into disease pathogenesis and therapeutic opportunities DOI
Yuting Qin, Jianyang Ma, Carola G. Vinuesa

et al.

Current Opinion in Rheumatology, Journal Year: 2024, Volume and Issue: 36(3), P. 191 - 200

Published: Feb. 29, 2024

Purpose of review This aims to provide an overview the genes and molecular pathways involved in monogenic lupus, implications for genome diagnosis, potential therapies targeting these mechanisms. Recent findings To date, more than 30 have been identified as contributors lupus. These are primarily related complement deficiency, activation type I interferon (IFN) pathway, disruption B-cell T-cell tolerance metabolic pathways, which reveal multifaceted nature systemic lupus erythematosus (SLE) pathogenesis. Summary In-depth study causes can valuable insights into pathogenic mechanisms SLE, facilitate identification effective biomarkers, aid developing therapeutic strategies.

Language: Английский

Citations

3
Gross Hematuria after the COVID-19 mRNA Vaccination: Nationwide Multicenter Prospective Cohort Study in Japan DOI Creative Commons
Ryousuke Aoki, Yoshihito Nihei, Keiichi Matsuzaki

et al.

Kidney360, Journal Year: 2024, Volume and Issue: 5(9), P. 1322 - 1332

Published: July 8, 2024

Key Points Little is known about the clinicopathological characteristics and renal outcomes in patients with gross hematuria (GH) after vaccination. To fill a knowledge gap regarding vaccination GH, we conducted nationwide multicenter prospective cohort study. GH more likely to occur IgA nephropathy, female bias, but without progressive exacerbation of function. Background In past 3 years, cases for coronavirus disease 2019 nephropathy (IgAN) have been frequently reported worldwide. However, postevent prognosis these patients, their clinical backgrounds, underlying mechanisms remain unknown. Therefore, study Japan. Methods We analyzed laboratory findings at time first presentation hospital 6 months histopathological kidney biopsy specimens. Moreover, changes pathological biomarkers IgAN such as galactose-deficient IgA1 (Gd-IgA1) its immune complexes were also evaluated. Results During period, 127 newly presenting enrolled, clear bias (73.2%). was observed second or subsequent vaccinations most (92.9%). Of 37 undergoing before vaccination, 36 had diagnosed IgAN/IgA vasculitis (IgAV). remaining 90 69 70 who underwent ( n =67)/IgAV =2). Their histopathology did not show high incidence acute lesions endocapillary hypercellularity crescentic lesions. Most showed temporary increase proteinuria, no sustained worsening Among measured, serum Gd-IgA1 comparable throughout observation period; however, only urinary increased GH. Conclusions found that IgAN/IgAV, Although further investigation needed causal relationship between this provides many insights into molecular

Language: Английский

Citations

3
How to treat monogenic SLE? DOI

Jonathan Thuner,

Jade Cognard,

Alexandre Bélot

et al.

Best Practice & Research Clinical Rheumatology, Journal Year: 2024, Volume and Issue: unknown, P. 101962 - 101962

Published: June 1, 2024

Language: Английский

Citations

2
Familial autoimmunity and risk of developing immune thrombocytopenia and Evans syndrome DOI
Michell Lozano Chinga, James B. Bussel, Mark Fluchel

et al.

Pediatric Blood & Cancer, Journal Year: 2024, Volume and Issue: 71(10)

Published: Aug. 3, 2024

Abstract Background Immune thrombocytopenia (ITP) and Evans syndrome (ES) are manifestations of immune dysregulation. Genetic variants in immune‐related genes have been identified patients with ITP especially ES. We aimed to explore familial autoimmunity ES understand possible contributions chronicity. Procedure assessed family history two ways: via patient report for by population‐based analysis using the Utah Population Database (UPDB) ITP. A total 266 21 were chart review, 252 also UPDB. Results Chart review showed 29/182 (15.9%) 25/84 (29.8%) newly diagnosed+persistent (nd+p) chronic (cITP), respectively, ( p = .009). The UPDB revealed that relatives nd+pITP was higher than controls (odds ratio [OR]: 1.69 [1.19–2.41], .004), but not significantly increased cITP (OR 1.10 [0.63–1.92], .734). Incomplete medical records likely contributed observed discrepancy. Conclusions findings suggest may a stronger association development rather its duration. Twelve (57.1%) reported their relatives. omitted due small number use population databases offers unique opportunity assess health provide clues about contributors dysregulation features within families.

Language: Английский

Citations

2