Systemic lupus erythematosus (SLE) is a complex autoimmune disease accompanied by production of autoantibodies directed to a variety of self-proteins and nucleic acids. The genetic basis of SLE is also complex with at least 40 susceptibility loci identified. This complexity suggests that there are a variety of SLE manifestations; nevertheless, SLE is treated as a single disease clinically. One unique SLE target is the Smith antigen (Sm), a nuclear ribonucleoprotein complex. Sm response occurs in 25% of patients with SLE. To simplify analysis of the disease and its associated autoantibody repertoire, we focused on this subset [referred to here as "Sm positive", Sm+]. We analyzed the memory B cell repertoire and identified a V region, Vκ4-1, which was significantly overrepresented in the Sm+ SLE subset. Antibodies that express Vκ4-1 are enriched in antinuclear (ANA) positive specificities and often associated with speckled ANA pattern that is a characteristic of Sm binding. In healthy individuals Vκ4-1 B cells are enriched in the unswitched memory population. Unswitched memory B cells resemble mouse marginal zone B cells and this population is decreased in all SLE patients. Moreover, we found a similar decrease in healthy African American donors. African Americans have a significantly higher prevalence of SLE compared to Caucasians. Thus, reduced unswitched memory B cell compartment may represent a new susceptibility marker for SLE.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.jaut.2018.02.008 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Altered immune surveillance of B and T cells in patients with persistent residual lung abnormalities 12 months after severe COVID-19.
Respir Res
January 2025
Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, 14080, Mexico.
Background: Post-COVID-19 respiratory sequelae often involve lung damage, which is called residual lung abnormalities, and potentially lead to chronic respiratory issues. The adaptive immune response, involving T-cells and B-cells, plays a critical role in pathogen control, inflammation, and tissue repair. However, the link between immune dysregulation and the development of residual lung abnormalities remains unclear.
View Article and Find Full Text PDFLipid-mediated resolution of inflammation and survival in amyotrophic lateral sclerosis.
Brain Commun
January 2025
Neuromuscular Department, Motor Neuron Disease Centre, Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
Neuroinflammation impacts on the progression of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. Specialized pro-resolving mediators trigger the resolution of inflammation. We investigate the specialized pro-resolving mediator blood profile and their receptors' expression in peripheral blood mononuclear cells in relation to survival in ALS.
View Article and Find Full Text PDFHypomorphic RAG2 Deficiency Promotes Selection of Self-Reactive B Cells.
J Clin Immunol
January 2025
Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA, USA.
Reduced function or hypomorphic variants in recombination-activating genes (RAG) 1 or 2 result in a broad clinical phenotype including common variable immunodeficiency (CVID) and even adult-onset disease. Milder RAG variants are less characterized. Here we describe the longitudinal course of a milder combined RAG deficiency in 3 of 7 siblings sharing the same RAG2 mutations over a 50-year study.
View Article and Find Full Text PDFEffect of Epstein-Barr Virus infection on gene regulation in immune cells of patients with Immune-Mediated Diseases.
J Autoimmun
January 2025
Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address:
It has been known that Epstein-Barr virus (EBV) can latently infect immune cells after the initial infection, and epidemiological studies have suggested its association with the onset of immune-mediated diseases (IMDs). However, the specific impact of EBV infection on IMDs pathology remains unclear. We quantified EBV load of B cell subsets (Naïve B cells, Unswitched memory B cells, Switched memory B cells, Double negative B cells, and Plasmablasts) in IMD patients as well as healthy control (HC) using bulk RNA sequencing data of 504 donors.
View Article and Find Full Text PDFIdentification of a broad-inhibition influenza neuraminidase antibody from pre-existing memory B cells.
Cell Host Microbe
January 2025
Zhejiang Key Laboratory of Multi-Omics in Infection and Immunity, Center for Infectious Disease Research, School of Medicine, Westlake University, Hangzhou, Zhejiang, China; Research Center for Industries of the Future, Westlake University, Hangzhou, Zhejiang, China; School of Life Science, Westlake University, Hangzhou, Zhejiang, China. Electronic address:
Identifying broadly reactive B precursor cells and conserved epitopes is crucial for developing a universal flu vaccine. In this study, using influenza neuraminidase (NA) mutant probes, we find that human pre-existing NA-specific memory B cells (MBCs) account for ∼0.25% of total MBCs, which are heterogeneous and dominated by class-unswitched MBCs.
View Article and Find Full Text PDFWant 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!