Potential Of Immunoglobulin Research Articles

Molecular and Cellular Pathways of Immunoglobulin G Activity In Vivo

In retrospect, the therapeutic potential of immunoglobulins was first demonstrated by von Behring and Kitasato in the late nineteenth century by protecting mice from the lethal effects caused by tetanus and diphtheria toxin via injection of a hyperimmune serum generated in rabbits. Even today, hyperimmune sera generated from human donors with high serum titers against a certain pathogen are still in use as a means of providing passive protection. More importantly, therapeutic antibodies specific for malignant or autoreactive cells have become included in the standard of care in diseases such as breast cancer and malignant lymphoma. Despite this clinical success, we are only at the beginning of understanding the precise molecular and cellular pathways responsible for immunoglobulin G (IgG) activity in vivo. Since then, an enormous amount of information about the mechanism of IgG activity has been obtained in various model systems. The aim of this review is to provide a comprehensive overview of our current understanding of how IgG antibodies mediate their activity in vivo and how we can use this knowledge to enhance the activity of therapeutic antibodies or block the proinflammatory and tissue pathology inducing activity of autoantibodies.

Recombinant IgM expression in mammalian cells: A target protein challenging biotechnological production

For many years, the potential of immunoglobulin M (IgM) antibodies was not fully understood because of characteristics different to the well-known immunoglobulin G type like low target affinity, cross reactivity and complex protein structure. In the meanwhile IgMs have been positively evaluated for their use as therapeutic agent in the mucosal environment but also in serum to eradicate upcoming tumor cells and invading antigens. Therefore IgM class of antibodies will play a significant role in clinical applications but also diagnosis in the future. To evaluate the full potential of this kind of antibody molecules large amounts of high quality product will be needed. In this review the focus is set on the biotechnological aspect of producing IgM class antibodies recombinantly in mammalian cells. Current achievements in expression and purification of this molecule are highlighted and compared.

Potential of Immunoglobulin A to Prevent Allergic Asthma

Allergic asthma is characterized by bronchial hyperresponsiveness, a defective barrier function, and eosinophilic lower airway inflammation in response to allergens. The inflammation is dominated by Th2 cells and IgE molecules and supplemented with Th17 cells in severe asthma. In contrast, in healthy individuals, allergen-specific IgA and IgG4 molecules are found but no IgE, and their T cells fail to proliferate in response to allergens, probably because of the development of regulatory processes that actively suppress responses to allergens. The presence of allergen-specific secretory IgA has drawn little attention so far, although a few epidemiological studies point at a reverse association between IgA levels and the incidence of allergic airway disease. This review highlights the latest literature on the role of mucosal IgA in protection against allergic airway disease, the mechanisms described to induce secretory IgA, and the role of (mucosal) dendritic cells in this process. Finally, we discuss how this information can be used to translate into the development of new therapies for allergic diseases based on, or supplemented with, IgA boosting strategies.

The application of IgM in an xMAP suspension assay using recombinant Alt a1 as a model target protein

The potential of Immunoglobulin M (IgM) in an Multi Analyte Profiling (xMAP) multiplex suspension assay was determined using Alt a1, a major allergen of Alternaria alternata, as the model target protein. LumAvidin (LAM) and carboxylated (CAM) microspheres, from LUMINEX™ Corporation, were compared. The reproducible standard curves for concentrations between 1 pg/mL and 10 ng/mL and 3 pg/mL and 300 ng/mL of the allergen were generated by the LAM assay, allowing for the quantitation of an unknown test sample. The success of the LAM assay is dependent on avidin molecules, initially bound on the microsphere, along with the use of a phycoerythrin-coupled secondary IgM. The standard curves generated by the CAM assay for the two allergen concentrations were erratic, falling short of quantifying the test sample. This is the first time a monoclonal IgM is successfully applied as a primary and secondary antibody in the xMAP format. The routine application of this assay will be consolidated as new IgM-based xMAP diagnostics become available.