Given the central role of antibody responses in allergic disease, we may now take advantage of these advances to improve our understanding of antibody allergen interactions and identify disease-relevant epitopes of clinically relevant allergens

Given the central role of antibody responses in allergic disease, we may now take advantage of these advances to improve our understanding of antibody allergen interactions and identify disease-relevant epitopes of clinically relevant allergens. allergen and has proven highly effective in the treatment of rhinitis, asthma, and venom allergy. Conventional AIT involves the subcutaneous injection of increasing doses of allergen extract over many years. Treatment carries a risk of inducing adverse side effects including systemic anaphylaxis [3]; hence, a major goal of research into AIT has been to improve both safety and efficacy. To this end, alternative routes of allergen administration have or are being successfully adopted (e.g., sublingual, oral, epicutaneous, intralymphatic). Novel vaccine design has led to the development of alternative forms of treatment including peptide immunotherapy, immunotherapy with recombinant allergens or modified allergen extracts, and the use of adjuvants that stimulate innate immune receptors. In addition, the combined use of monoclonal antibody therapy alongside AIT has proven highly successful. Monoclonal antibodies (mAbs) have revolutionized the way we diagnose and treat human TPCA-1 disease. Of the mAbs now approved or Rabbit Polyclonal to ZNF446 under review, the overwhelming majority are licensed for use TPCA-1 in cancer or autoimmune diseases. Until recently, the only mAb in clinical use for allergic disease was the anti-IgE antibody Omalizumab (Xolair), which was approved in the USA in 2003 and in Europe in 2005 for patients with asthma. In addition, the anti-IL-5 antibody Mepolizumab has now been approved for use in severe eosinophilic asthma. Rapid technological advances in medicine over recent years provide an opportunity to reassess TPCA-1 our understanding of allergic diseases and our approach to AIT. The aims of this review are to assess how advances in monoclonal antibody technology could impact the field of allergy and in particular address some of the challenges of allergen immunotherapy. == The Breadth of the Humoral Response == Antibodies are secreted glyco-proteins that recognize and bind to antigen with exquisite specificity through the highly variable fragment antigen binding (Fab) region (Fig.1). The various effector functions of antibodies are elicited via the fragment crystallizable (Fc) region (Fig.1), through engagement with Fc receptors and other components of the immune system. == Fig. 1. == Human Immunoglobulins. Schematic representation of the human immunoglobulin subclasses, monomeric IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgD, IgE, and polymeric (p) IgA and IgM Human antibodies are encoded within the heavy chain immunoglobulin locus on chromosome 14 (VH, D, JH, and CH), the kappa () light chain immunoglobulin locus on chromosome 2 (V, J and C), and the lambda () light chain locus on chromosome 22 (V, J, and C). Antibodies are produced by B cells which develop in the bone marrow and express a membrane version of the antibody in the form of a B cell receptor or membrane immunoglobulin. Following activation by antigen in the periphery, specific B cells undergo a series of processes that involve clonal proliferation, isotype switching (or class switch recombination), and affinity maturation, whereby somatic hypermutation of variable region genes leads to changes in the affinity of the BCR. B cells that bind to antigen with high affinity receive survival signals and may differentiate into memory B cells or plasma cells, the latter of which gives rise to secretion of TPCA-1 high affinity antibodies. Long-lived, terminally differentiated plasma cells migrate to the bone marrow where they are thought TPCA-1 to produce in excess of 108antibody molecules per hour [4]. Human antibodies are grouped into five classes (IgD, IgM, IgA, IgE, and IgG, Fig.1) with IgA and IgG further divided into two and four subclasses (IgA1 and IgA2, IgG1, IgG2, IgG3, and IgG4), respectively, [5]. IgM is expressed as a monomer on the cell surface during B cell development. Following maturation, IgM is secreted by activated B cells as a pentamer or, less commonly as a hexamer, with the addition of the J-chain (Fig.1). The multimeric structure of IgM increases avidity of antigen binding thus enhancing its.