Expert review of clinical immunology
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Mepolizumab (Bosatria(®), GlaxoSmithKline) is a biologic agent developed to treat asthma. It represents a humanized monoclonal antibody of IgG1 κ type, which targets human IL-5 and thus prevents its interaction with the α-chain of the IL-5 receptor. To date, it has not been approved for use in any eosinophil-related disorder; however, several studies have suggested some therapeutic benefit across a spectrum of eosinophil-related disorders. This article evaluates the currently available preclinical and clinical studies, and the impact of mepolizumab against a variety of eosinophilic disorders.
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Expert Rev Clin Immunol · Jan 2011
ReviewAcute infusion reactions induced by monoclonal antibody therapy.
This article reports recent evidence on epidemiological data concerning monoclonal antibody (mAb) infusion-related anaphylaxis, as well as recent data on the correlation between mAb immunogenicity and safety profiles. Pathogenic mechanisms of mAb-related adverse reactions including hypersensitivity, IgE- and non-IgE-mediated events and cytokine release syndrome are also highlighted. Finally, the role of serum anti-mAb antibodies as markers to monitor the safety of such therapeutical compounds are extensively evaluated. The anaphylaxis occurring during therapy with the anti-TNF-α mAb infliximab, largely used in immune-mediated diseases, has been taken as a paradigm.
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Expert Rev Clin Immunol · Nov 2010
ReviewFinding the right time for weaning off immunosuppression in solid organ transplant recipients.
Solid organ transplantation (SOT) requires lifelong immunosuppression (IS) to prevent rejection and graft loss. The currently adopted immunosuppressive protocols are numerous and are based on the administration of at least two molecules with diverse mechanisms of action. Owing to the fact that the majority of immunosuppressants act non-selectively, the immune system is normally oversuppressed, and as a result is less able to both defend the host against infection and to control the spread of malignant cells. ⋯ On the contrary, COT remains a major challenge after RT because the onset of acute rejection will substantiate in graft loss. Currently, a major field of investigation aims to define markers of COT, which will allow the selection of individuals who are more prone to develop COT. Preliminary results in both RT and LT have just been announced; however, these markers will require validation in prospective studies.
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Inflammatory mediators, adhesion molecules of neutrophils and monocytes, have been shown to be increased in the plasma of patients presenting with acute coronary syndromes. Anaphylaxis is a systemic, immediate hypersensitivity reaction caused by rapid IgE-mediated release of mediators from mast cells and basophils. Kounis syndrome is the coincidental occurrence of these two distinct conditions accompanied by clinical and laboratory findings of angina pectoris caused by inflammatory mediators released during an allergic insult. ⋯ There are several causes reported to be capable of inducing Kounis syndrome. These include a number of conditions, several drugs, foods and insect stings, among others. In this article, the clinical aspects, diagnosis, pathogenesis, incidence and epidemiology, related conditions and therapeutic management of this important syndrome are discussed.
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Expert Rev Clin Immunol · Jul 2010
ReviewCurrent status of monoclonal antibody therapy for the treatment of inflammatory bowel disease.
Crohn's disease and ulcerative colitis are complex diseases that have required the use of multiple modalities to aid in treatment. With an increasing understanding of the underlying pathogenetic mechanisms and identification of specific therapeutic targets, monoclonal antibody treatment has been an ideal strategy for inducing and maintaining remission in these patients. This article addresses approved agents and the supporting data justifying their use in Crohn's disease and ulcerative colitis, the safety of and immunologic reactions to these agents, as well as newer agents for treatment.