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Mucosal B cells and their function
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Jo Spencer, Edward N. Janoff, Per Brandtzaeg
Germinal center B cells undergo modification of DNA sequences through the activity of AID, the B-cell–specific enzyme that catalyzes the mutation of target DNA sequences (Figure 10.5). AID is upregulated in B cells following engagement of the B-cell receptor or toll-like receptors by microbial antigens to effect somatic hypermutation and class-switch recombination. Mutations in the functional domains of AID in Type 2 hyper-IgM syndrome lead to the absence of germinal centers, IgA and other class-switched immunoglobulins, and somatic hypermutation, underscoring the importance of AID.
Immunology (primary Immunodeficiency Syndromes
Published in Stephan Strobel, Lewis Spitz, Stephen D. Marks, Great Ormond Street Handbook of Paediatrics, 2019
Stephan Strobel, Alison M. Jones
All types require immunoglobulin replacement. Boys affected by X-linked hyper-IgM syndrome require prophylaxis against Pneumocystis jirovecii with cotrimoxazole, and anticryptosporidial precautions (boil drinking water). SCT is recommended if a suitable donor is available.
Management of cryptococcosis
Published in Mahmoud A. Ghannoum, John R. Perfect, Antifungal Therapy, 2019
Cryptococcal disease occurs less frequently in children than in adults. There are some unique childhood conditions, such as Hyper IgM Syndrome, Severe Combined Immunodeficiency Syndrome, Acute Lymphoblastic Leukemia, and Sarcoma, associated with pediatric cryptococcosis. In general, pediatric meningoencephalitis is treated like it is with an adult except higher doses of amphotericin B and lipid formulations can be used, and, similarly, fluconazole dosing is increased to approximate a child’s metabolism and clearance [124,125].
Genetic Analysis of Patients with Two Different Types of Hyper IgM Syndrome
Published in Immunological Investigations, 2018
Zahra Alizadeh, Marzieh Mazinani, Masoud Houshmand, Leila Shakerian, Maryam Nourizadeh, Zahra Pourpak, Mohammad Reza Fazlollahi
Herein, we reported the clinical and genetic features of six Iranian HIGM patients introducing two novel mutations. Hyper IgM syndrome is a heterogeneous disorder in which defects in several genes have been associated. Depend on which defective gene being involved, the clinical manifestations vary from mild bacterial infections, observed in AID deficiency, to both cellular and humeral defects in CD40L deficiency (Picard et al., 2015). CD40L, which is expressed on the surface of activated CD4 + T cells, through interactions with its receptor (CD40) on the surface of B cells, monocytes/macrophage and dendritic cells contributes in both innate and adaptive immunity. Therefore, patients with defective CD40L usually show more complicated clinical phenotype compared to patients with AID deficiency, which is an intrinsic defect restricted to B cells (Notarangelo, 2010). Recent studies have intensively evaluated the role of CD40L-CD40 interaction in both macrophages and neutrophils development and function and introduced a recombinant human IFN-γ (rhIFN-γ) as a novel therapeutical approach to improve the immune responses in CD40L-deficient patients with neutropenia (Cabral-Marques et al., 2017, 2018).
Factors associated with serum IgM concentrations: a general adult population study
Published in Scandinavian Journal of Clinical and Laboratory Investigation, 2021
Iago Carballo, Manuela Alonso-Sampedro, Rosa-María Escribano, Carmen Fernandez-Merino, Bernardo Sopeña, Carmen Vidal, Francisco Gude, Arturo Gonzalez-Quintela
Immunoglobulin M (IgM) is the most preserved antibody class in evolution, being present in all vertebrate species. Although the existence of IgM has been known for many decades, its biological significance in health and disease continues to emerge, as recent reviews have shown [1,2]. Serum concentrations of specific IgM are commonly employed in clinical practice to detect primary antibody response and therefore serve to diagnose recent infection by a given pathogen. Specific IgM autoantibodies are also a useful diagnostic tool in autoimmune diseases, such as multiple sclerosis, and in some forms of autoimmune hemolytic anemia and cryoglobulinemia [3]. Examples of specific forms of IgM that are employed in diagnosis include isohemagglutinins of blood groups [4], rheumatoid factor in a variety of diseases [5], and the heterophile antibody during infectious mononucleosis [6]. Increased serum concentrations of total IgM are frequently found in primary biliary cholangitis, a liver autoimmune disease characterized by the destruction of intrahepatic bile ducts, with accompanying portal inflammation and progressive fibrosis [7,8]. The serum concentration of IgM paraprotein is a hallmark of certain monoclonal plasma cell neoplasms, such as Waldenström macroglobulinemia [9]. Rare forms of IgM-related immunodeficiency include selective IgM deficiency and hyper-IgM syndromes. Selective IgM deficiency is a disorder characterized by the isolated absence or deficiency of IgM and normal levels of other immunoglobulins, notably IgG and IgA, and normal T-cell function [10]. In addition to infections, selective IgM deficiency can be accompanied by immune disorders, such as autoimmune and allergic diseases [10]. Hyper-IgM syndromes are a heterogeneous group of conditions characterized by defective class-switch recombination, mostly X-linked, caused by mutations in the CD40 ligand gene, resulting in normal or increased serum IgM levels associated with deficiency of IgG, IgA, and IgE, and poor antibody function [11]. In addition to infections, hyper-IgM syndromes can be accompanied by hematologic abnormalities, lymphoproliferation, autoimmune disease, and malignancies [11].
Inflammatory bowel diseases and primary immunodeficiency diseases
Published in Immunological Medicine, 2018
IBD is typically diagnosed from endoscopic and histopathological observations. The histopathology of IBD is classified as CD, UC, or IBD unclassified, and the latter is frequently observed in patients with VEOIBD, especially those with monogenic IBD. Various functional and genetic tests are required to confirm monogenic IBD in patients with VEOID (Figure 3). These include analyses of neutrophil-mediated oxidative bursts using nitroblue tetrazolium tests or flow cytometry-based assays, measurements of IgG, IgA, IgM, and IgE, and flow cytometric assays of lymphocyte subsets, such as CD3+ T, CD4+ T, CD8+ T, CD19/C20+ B, and CD16/CD56+ natural killer (NK) cells. All types of chronic granulomatous disease can be diagnosed using assays of the neutrophil oxidative burst. Patients with common variable immunodeficiency and agammaglobulinemia show reduced levels of all class immunoglobulins. Patients with hyper IgM syndrome generally have normal to elevated levels of IgM but reduced levels of IgG and IgA. Elevated levels of IgE and/or eosinophilia are also observed in patients with monogenic defects in FOXP3, IL2RA, IKBKG, WAS, or DOCK8 genes. Whereas all patients with severe combined immunodeficiency (SCID) lack T cells, the associated impact on B and NK cells vary between genetic defects. For example, X-linked agammaglobulinemia is associated with reduced numbers of circulating B cells. Moreover, FOXP3 expression in CD4+CD25+ T cells is reduced in a proportion of patients with immune dysregulation, polyendocrinopathy, enteropathy, and X-linked (IPEX) syndrome [16,17]. XIAP expression is decreased in lymphocytes and monocytes of some patients with XIAP deficiency (Figure 4(a)) [17,18], and muramyl dipeptide signaling is selectively defective in patients with XIAP deficiency (Figure 4(b)) [19]. IL-10 receptor deficiency can also be detected using assays that determine whether exogenous IL-10 suppresses lipopolysaccharide-induced cytokine production in peripheral blood mononuclear cells [20,21]. Following functional screening of these deficiencies, candidate genes are generally sequenced to confirm the suspected genetic condition.