Blocking of Histamine Release and IgE Binding to FcepsilonRI on Human Basophils by Antibodies Produced in Camels

PURPOSE: The production of camel heavy-chain antihuman IgE (huIgE) that has the potential to block IgE-FcepsilonRI interaction and histamine release by basophils. METHODS: Camels were immunized with a synthetic loop peptide (SLP) designed in a multiple antigen peptide system (MAPS) forming SLP-MAPS immunogen. Camel polyclonal antibodies (PCAs) were produced, purified, characterized using Protein A & G, ELISA, and SDS-PAGE, and tested for their potency to block passive sensitization and histamine release of human basophils using flow cytometry (FCM) and ELISA, respectively. RESULTS: FCM data indicated that camel conventional (IgG1) and heavy chain antibodies (HCAbs; IgG2, and IgG3) had blocking activities of 43.9%, 72%, and 96.6%, respectively. Moreover, both IgG2 and IgG3 achieved remarkable inhibition rates of 93.98% and 97.05% in histamine release, respectively, whereas the IgG1inhibiting activity was 60.05%. CONCLUSIONS: Camel PCAs produced against SLP-MAPS were capable of blocking the IgE-receptor interaction and the release of histamine by basophils with superiority to HCAbs. These findings may pave the way toward the possible use of camel anti-huIgE HCAbs as blocking antibodies in the treatment of IgE-mediated allergy and asthma.

Newer approaches in the treatment of asthma.

Asthma is a worldwide public health problem. The most effective anti-asthmatic drugs - inhaled β2-agonists and glucocorticoids controls asthma in about 90-95% of patients. However, severe glucocorticoid-dependent and resistant asthma presents a great clinical burden. Therefore, reducing glucocorticoids - related adverse effects using novel steroid-sparing agents is needed. Furthermore, the mechanisms involved in the persistence of inflammation are poorly understood and the reasons why some patients have severe life threatening asthma and others have very mild disease are still unknown. Although glucocorticoids effectively control the inflammatory process in asthma, they have little effect on the lower airway remodeling processes that appear to play a role in the pathophysiology of asthma. Several new drugs developed to target specific components of the inflammatory process in asthma [e.g. anti-IgE antibodies (omalizumab), cytokines and/or chemokines antagonists, immunomodulators, antagonists of adhesion molecules)], have not yet been proven to be particularly effective. Hence, considering the central role of T lymphocytes in the pathogenesis of asthma, drugs targeting disease-inducing Th2 cells are promising future therapeutic strategies. Some of these new anti-asthmatic treatment approaches may in the future not only control symptoms and modify the natural course of asthma, but also potentially prevent or cure the disease. Hence, the development of novel drugs may allow resolution of these changes.