Defects of memory B cells and of somatic hypermutation (SHM) are involved in the pathogenesis of common variable immunodeficiency (CVID). Here we report for the first time a systematic study of the relationship between memory B cell deficiency and SHM abnormalities in CVID, and relate these variables to prediagnostic infections. Isotype switched Vh3-23 transcripts were undetectable or low in 30% (IgG) and 63% (IgA) of the patients, but never in controls (P < 0.001). When measurable, the SHM fraction of transcripts was significantly lower in patients (IgM: median 32% vs. 56% (P = 0.0002); IgG: 72% vs. 87% (P = 0.0002); IgA: 81% vs. 88% (P = 0.04)). The concentration of switched (CD19+/CD27+/IgG+) and unswitched (CD19+/CD27+/IgM+/IgD+) memory cells was reduced in 75% and 58% of the patients, respectively. Patients with reduced concentrations of switched memory B cells had normal or low SHM, and only the IgG SHM fraction correlated with prediagnostic incidence of severe respiratory tract infections (P = 0.004).
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Cytometry B Clin Cytom
January 2025
Department of Pediatrics, Section of Allergy and Immunology, University of Colorado School of Medicine, Aurora, Colorado, USA.
A reduced proportion of peripheral class-switched memory B cells (CSM-B cells) is presumed to indicate ineffective germinal activity. The extent that this finding corresponds to a plausible germinal center failure pathophysiology in patients not diagnosed with CVID or hyper IgM syndrome is not known. We asked if patients with low CSM-B cells are more likely to demonstrate failure to produce serum IgA and IgG than counterparts with nonreduced class-switched memory B cell levels, regardless of diagnosis.
View Article and Find Full Text PDFEndocr Metab Immune Disord Drug Targets
January 2025
Department of Radiotherapy, Suzhou Ninth People's Hospital, Suzhou, 215200, China.
Background: Liquid-Liquid Phase Separation (LLPS) is a process involved in the formation of established organelles and various condensates that lack membranes; however, the relationship between LLPS and Ulcerative Colitis (UC) remains unclear.
Aims: This study aimed to comprehensively clarify the correlation between ulcerative colitis (UC) and liquid-liquid phase separation (LLPS).
Objectives: In this study, bioinformatics analyses and public databases were applied to screen and validate key genes associated with LLPS in UC.
Front Immunol
January 2025
Leiden University Center for Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands.
Introduction: Tuberculosis (TB) is the deadliest infectious disease worldwide and novel vaccines are urgently needed. HLA-E is a virtually monomorphic antigen presentation molecule and is not downregulated upon HIV co-infection. HLA-E restricted specific CD8 T cells are present in the circulation of individuals with active TB (aTB) and infection (TBI) with or without HIV co-infection, making HLA-E restricted T cells interesting vaccination targets for TB.
View Article and Find Full Text PDFEur J Case Rep Intern Med
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Clínica de Medicina, Serviço de Medicina Interna, Centro Hospitalar Universitário de Santo António, Porto, Portugal.
Unlabelled: Sarcoidosis is a multisystemic syndrome characterized by non-caseous granulomatous inflammation, although necrotizing sarcoid granulomatosis is considered part of the spectrum of the disease. Drug induced sarcoidosis-like reaction (DISR) is a systemic granulomatous reaction, which is histopathologically identical to primary sarcoidosis - mostly described after the use of biologics like tumour necrosis factor alpha antagonists but also anti-CD20 (rituximab). The authors present the very rare case of a woman with a primary Sjögren's syndrome (pSS) started on rituximab for disease control, which evolved with a 3-year indolent progressive systemic sarcoid reaction.
View Article and Find Full Text PDFCurr Protoc
January 2025
Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland.
In vivo calcium imaging in freely moving rats using miniscopes provides valuable information about the neural mechanisms of behavior in real time. A gradient index (GRIN) lens can be implanted in deep brain structures to relay activity from single neurons. While such procedures have been successful in mice, few reports provide detailed procedures for successful surgery and long-term imaging in rats, which are better suited for studying complex human behaviors.
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