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Hypomorphic 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 PDFUse of Immunoglobulin Replacement Therapy in Clinical Practice: A Review.
J Immunother Precis Oncol
February 2025
Department of Pediatrics, Division of Immunology, Allergy and Retrovirology, Baylor College of Medicine, Houston, TX, USA.
Immunoglobulins (Igs) are produced by B lymphocytes and play a key role in humoral immunity. Igs are classified into five isotypes (IgG, IgA, IgM, IgE, and IgD). Their primary function is to recognize and bind to foreign antigens.
View Article and Find Full Text PDFAllergic Reactivity and Memory Occur Independently of Sequential Switching Through IgG1.
Allergy
January 2025
Schroeder Allergy and Immunology Research Institute, Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Canada.
Allergic reactions to foods are primarily driven by allergen-binding immunoglobulin (Ig)E antibodies. IgE-expressing cells can be generated through direct switching from IgM to IgE or a sequential class switching pathway where activated B cells first switch to an intermediary isotype, most frequently IgG1, and then to IgE. It has been proposed that sequential class switch recombination is involved in augmenting the severity of allergic reactions, generating high affinity IgE, differentiation of IgE plasma cells, and in holding the memory of IgE responses.
View Article and Find Full Text PDFLongitudinal monitoring of class-switched memory-B cell proportions identifies plausible germinal center failure in patients with suspected immune disorders.
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 PDFEffects of Baseline Blood Zinc Levels on the Humoral Immune Response After COVID-19 mRNA Vaccination: A Prospective Study in a Japanese Population.
Vaccines (Basel)
November 2024
Department of Social and Environmental Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan.
Background/objectives: Although the protective effects of zinc against COVID-19 are documented, its impact on COVID-19 vaccine immunogenicity remains unknown.
Methods: We conducted a prospective study involving a cohort of 79 Japanese individuals (aged 21-56 years; comprising three subcohorts) and measured their serum zinc levels pre-vaccination and anti-SARS-CoV-2 IgM/IgG levels pre- and post-vaccination over 4 months.
Results: Serum zinc concentrations ranged between 74-140 and 64-113 μg/dL in male and female individuals, respectively, with one male and 11 female participants exhibiting subclinical zinc deficiency (60-80 μg/dL).
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