Isotypes, in humans

Maizels, R.M., Sartono, E., Kurniawan, A, Partono, F., Selkirk, M.E. and Yazdanbash, M. (1995) T-cell activation and the balance of antibody isotypes in human lymphatic filariasis. Parasitology Today 11, 50-56. 

Murray NR, Baumgardner GP, Burns DJ, Fields AP (1993) Protein kinase C isotypes in human erythroleukemia (K562) cell proliferation and differentiation. Evidence that beta II protein kinase C is required for proliferation. J Biol Chem 268 15847-15853... 

Cytokines play an important role in the control of switching of antibody isotypes in humans away from IgM during the evolution of the immune response. Cytokines which play a role in this process may be classified as follows. 

Lysine methyltransferases have been linked in various cases to the pathogenesis of cancer. Examples can be found for KMTs that induce repressive marks as well as for those that lead to an activating methylation pattern. Possible reasons for a disturbed regulation of methylation may result in mutations of enzymes or overexpression in cancer cells. An indication for a therapeutic benefit of potential inhibitors is often derived from siRNA knockdown of the requisite isotype. Mutations of MLLl for example are thought to be responsible for various forms of acute leukemia [63]. Overexpression of EZH2 was linked to breast or prostate cancer [64] and increased levels in human cancers have also been observed for G9a. Increased mRNA levels for... 

The major antibody isotype in external secretions is sIgA, and the total amount of IgA synthesized is twice the amount of IgG produced daily in humans. IgA cells represent up to 80% of the entire mucosal lymphoid cell population. sIgA in mucosal secretions results from polymeric IgA transported across mucosal epithelium via binding to the pIgRreceptor (also known as the secretory component). The receptor is eventually cleaved and results in an IgAipIgR complex, referred to as sIgA (Figure 7.2) (Rojas and Apodaca, 2002). 

In humans, there are five isotypes of antibodies, IgG, IgA, IgD, IgE, and IgM, which are defined by the structures of their heavy chains and their abilities to form multimers (Figure 10.1) [8], IgG is the most abundant isotype present in serum with average serum concentrations ranging from 0.5 to 9mg/ml depending on the IgG subtype. This is followed by IgA (3mg/ml), IgM (1.5mg/ml), IgE (0.05 mg/ml), and IgD (trace). Each antibody isotype has unique functions. Critical functions of IgG include opsonization, complement activation, antibody-dependent cell-mediated cytotoxicity (ADCC), passive immunity, and regulation of B cells. Both IgM and IgD act as antigen receptors on naive B cells, and soluble, multimeric forms of IgM are involved in complement activation. IgA is involved in mucosal and passive neonatal immunity, while IgE is involved in immediate hypersensitivity [8],... 

Tissue cross-reactivity studies, although burdensome, provide a rational in vitro assay to determine the range and intensity of distribution of potential epitopes reactive with a monoclonal antibody test article prior to its administration to humans. In addition, cross-reactivity studies provide a useful tool to identify animal species for safety assessment. The cross-reactivity profiles of different species can be compared to the profiles obtained in human tissues. The predictive value of the assay lies in incorporating the characteristics of the monoclonal antibody (isotype, subtype, and other molecular modifications) with the biological activity of the molecule itself, and the potential in vivo distribution of it. 

Chicken and rat VAMP-1 is not cleaved by CNTs (Schiavo ef al., 1992 a, 1994 Patarnello et al., 1993). These VAMP isotypes contain a Val residue in place of the Gin residue at the cleavage site of TeTx and BoNT/B in human and mouse VAMP-1. It has been proposed that this single amino acid replacement at the cleavage site is associated with the resistance of rats and chickens to tetanus and type B botulism (Patarnello ef al., 1993). The differential susceptibility to TeTx and BoNT/B proteolysis of rat VAMP-1 and -2 has been used to identify the VAMP isotypes (Braun ef al., 1994 Steinhardt ef al., 1994). On the other hand, BoNT/D, F and G cleave both VAMP-1 and -2 at similar rates. 

Murine IgG does not bind to human FcRn, and this explains the shorter half life of murine antibodies in human patients, typically 12 to 48 h [91]. The half lives of endogenous human IgG isotypes have been well studied and they do differ - 3 weeks for IgGl, IgG2 and IgG4, while IgG3 has a half-Hfe of 1 week [88, 92]. 

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