Monoclonal antibodies have become an essential treatment modality for many inflammatory diseases and malignancies. Hypersensitivity reactions to monoclonal antibodies need not prevent their use as first-line therapy. Through the use of rapid desensitization, the patient may be safely re-exposed to the agent. In this article, we review the algorithm for rapid desensitization of monoclonal antibodies.

The IL-4Rα R576 polymorphism has been associated with increased disease severity scores in a large cohort of patients with Atopic Dermatitis (AD), and exaggerates allergic skin inflammation and the systemic Th2 response in an antigen driven mouse model of AD. We examined whether the polymorphism is associated with higher Th2 biomarker levels in AD.

BACKGROUND:Atopic dermatitis (AD) is characterized by TH2-dominated skin inflammation and systemic response to cutaneously encountered antigens. The TH2 cytokines IL-4 and IL-13 play a critical role in the pathogenesis of AD. The Q576->R576 polymorphism in the IL-4 receptor alpha (IL-4Rα) chain common to IL-4 and IL-13 receptors alters IL-4 signaling and is associated with asthma severity.OBJECTIVE:We sought to investigate whether the IL-4Rα R576 polymorphism is associated with AD severity and exaggerates allergic skin inflammation in mice.METHODS:Nighttime itching interfering with sleep, Rajka-Langeland, and Eczema Area and Severity Index scores were used to assess AD severity. Allergic skin inflammation following epicutaneous sensitization of mice 1 or 2 IL-4Rα R576 alleles (QR and RR) and IL-4Rα Q576 (QQ) controls was assessed by flow cytometric analysis of cells and quantitative RT-PCR analysis of cytokines in skin.RESULTS:The frequency of nighttime itching in 190 asthmatic inner-city children with AD, as well as Rajka-Langeland and Eczema Area and Severity Index scores in 1116 White patients with AD enrolled in the Atopic Dermatitis Research Network, was higher in subjects with the IL-4Rα R576 polymorphism compared with those without, with statistical significance for the Rajka-Langeland score. Following epicutaneous sensitization of mice with ovalbumin or house dust mite, skin infiltration by CD4+ cells and eosinophils, cutaneous expression of Il4 and Il13, transepidermal water loss, antigen-specific IgE antibody levels, and IL-13 secretion by antigen-stimulated splenocytes were significantly higher in RR and QR mice compared with QQ controls. Bone marrow radiation chimeras demonstrated that both hematopoietic cells and stromal cells contribute to the mutants' exaggerated allergic skin inflammation.CONCLUSIONS:The IL-4Rα R576 polymorphism predisposes to more severe AD and increases allergic skin inflammation in mice.