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The Inducible Defense System: Antibody Molecules and Antigen-Antibody Reactions
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
IgM has a molecular weight of 900,000 and is a pentamer of five subunits in a circular configuration joined by disulfide bridges (Figure 7.4). An additional polypeptide chain, called the J chain, helps stabilize the molecule. The J chain (M.W. 15,000 daltons) is coded for by a non-Ig gene. IgM is the largest molecule of any antibody of the five classes; because of its size, it circulates primarily in the vascular blood compartment. IgM is the first antibody to be made during a primary immune response. It is an efficient activator of the complement cascade, since only one bound IgM molecule is needed to lyse a cell. On the other hand, IgG requires two or more bound molecules to activate complement.
Case 23
Published in Andrew Solomon, Julia Anstey, Liora Wittner, Priti Dutta, Clinical Cases, 2021
Andrew Solomon, Julia Anstey, Liora Wittner, Priti Dutta
PrimaryCombined variable immunodeficiency – variable defects in immunoglobulins and/or T-cells, depending on precise mutationsX-linked (Bruton's) agammaglobulinaemia – mutations blocking B-cell maturation, so very low levels of immunoglobulin producedDiGeorge syndrome – absent or hypoplastic thymus leading to T-cell deficienciesHyper IgM syndrome – patients have abnormal T-cells so are unable to undergo immunoglobulin isotype switching. As a result, IgM levels are normal or high, but levels of IgG, IgA and IgE are lowSevere combined immunodeficiency – mutation leading to abnormal interleukin receptors prevents maturation of all aspects of the immune system. This results in low levels of T-cells, low levels of NK cells and normal numbers of non-functional B-cells
Multiple Myeloma
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
The diagnosis of myeloma is usually made by the demonstration of a monoclonal protein (M-protein/paraprotein) in the serum or urine and/or lytic lesions on X-ray/cross-sectional imaging together with an increased number of plasma cells in the bone marrow. The definition of myeloma was given by the IMWG in 2014 (Table 31.2). There are many other conditions in which an M-protein may be present (MGUS, AL amyloidosis, plasmacytoma, any B cell non-Hodgkin lymphoma, chronic lymphocytic leukemia, connective tissue disorders). An IgM monoclonal protein is usually associated with Waldenstroms macroglobulinemia or IgM MGUS, although rare cases of IgM myeloma do occur.
Therapeutic antibodies for COVID-19: is a new age of IgM, IgA and bispecific antibodies coming?
Published in mAbs, 2022
Jingjing Zhang, Han Zhang, Litao Sun
Traditionally, IgM antibodies have proven difficult to express and purify due to their large size and complexity. Thanks to advances in manufacturing, engineered IgM antibodies such as IgM-1433 can be produced with good quality, and it will be administered by intranasal and intraoral spray in clinical trials. In fact, several engineered IgM antibodies are being investigated in oncology clinical trials, and more than half of these IgM target antigens that are poorly immunogenic, which makes it difficult to generate IgG mAbs.16 However, multivalent antibodies, like IgM, might have an off-target effects, resulting in low affinity, less specificity and unexpected toxicities. Nonetheless, the use of IgM is anticipated as an essential approach to defend against complex pathogen infections, especially viruses that are difficult to target.
Local Steroid Treatment: An Effective Procedure for Idiopathic Granulomatous Mastitis, Including Complicated Cases
Published in Journal of Investigative Surgery, 2021
Taha Furkan Ertürk, Özgür Çakır, Büşra Yaprak Bayrak, Abdullah Güneş, Selahattin Aydemir, Nihat Zafer Utkan
Idiopathic granulomatous mastitis (IGM) is a benign and chronic inflammatory disease of the mammary gland and affected patients are usually women with a recent history of pregnancy and breastfeeding [1]. Rarely, IGM has also been reported in nulliparous women and men [2, 3]. Unlike other inflammatory diseases of the breast, it mimics breast cancer clinically and radiologically [1, 2, 4]. The pathogenesis of IGM remains unclear although evidence suggests this is likely to be autoimmune in nature. However, a number of risk factors have been identified including breastfeeding, use of the oral contraceptive pills, and preexisting autoimmunity. Additional risk factors include smoking, infection with undetectable microorganisms or infection with some Corynebacterium species and diabetes mellitus [1, 5].
A Novel CD40L Mutation Associated with X-Linked Hyper IgM Syndrome in a Chinese Family
Published in Immunological Investigations, 2020
Liangshan Li, Jing Ji, Mengmeng Han, Yinglei Xu, Xiao Zhang, Wenmiao Liu, Shiguo Liu
In this study, we identified a novel deletion mutation in CD40L by WES combined with Sanger sequencing in the family with XHIGM. CD40L, located on the X chromosome, contains 4 introns and 5 exons spanning 12214 bp. CD40L protein includes three domains among which the extracellular region contains 215 amino acids and has high homology with TNF at the amino acid level (Notarangelo and Hayward, 2000). CD40, the receptor of CD40L, is a type I transmembrane glycoprotein with 277 amino acids (Chatzigeorgiou et al., 2009) belonging to TNF receptor family, and is mainly detected on the surface of B cells, monocytes, epithelial cells, dendritic cells (Chatzigeorgiou et al., 2009; Grammer et al., 1995; Henn et al., 1998) and vascular endothelial cells (Hollenbaugh et al., 1995). In XHIGM individuals, B cells cannot undergo immunoglobulin class switch from IgM to IgG, IgA and IgE due to the inability to express CD40L on activated T cells. The interaction between B cells and T cells affects the activation of B cells (Schonbeck and Libby, 2001). Consequently, patients have normal or increased IgM with low levels of other types of immunoglobulin.