Hypersensitivity reactions monoclonal antibody

Rituximab is a monoclonal antibody to the CD20 receptor expressed on the surface of B lymphocytes the presence of the antibody is determined during flow cytometry of the tumor cells. Cell death results from antibody-dependent cellular cytotoxicity. The pharmacokinetics of rituximab are best described by a two-compartment model, with a terminal half-life of 76 hours after the first infusion and a terminal half-life of 205 hours after the fourth dose.36 Rituximab has shown clinical activity in the treatment of B-cell lymphomas that are CD20+. Side effects include hypersensitivity reactions, hypotension, fevers, chills, rash, headache, and mild nausea and vomiting. 

The adverse effects of ALG are mostly those associated with injection of a foreign protein. Local pain and erythema often occur at the injection site (type III hypersensitivity). Since the humoral antibody mechanism remains active, skin-reactive and precipitating antibodies may be formed against the foreign IgG. Similar reactions occur with monoclonal antibodies of murine origin, and reactions thought to be caused by the release of cytokines by T cells and monocytes have also been described. 

Immune vasculitis can also be induced by drugs. The sulfonamides, penicillin, thiouracil, anticonvulsants, and iodides have all been implicated in the initiation of hypersensitivity angiitis. Erythema multiforme is a relatively mild vasculitic skin disorder that may be secondary to drug hypersensitivity. Stevens-Johnson syndrome is probably a more severe form of this hypersensitivity reaction and consists of erythema multiforme, arthritis, nephritis, central nervous system abnormalities, and myocarditis. It has frequently been associated with sulfonamide therapy. Administration of nonhuman monoclonal or polyclonal antibodies such as rattlesnake antivenin may cause serum sickness. 

Several types of hypersensitivity reactions can occur in the host receiving monoclonal antibody therapy, and the tissue cross-reactivity study might be predictive of some of these hypersensitivity reactions. Theoretically, adverse reactions result in tissue destruction because of the activation of complement or release... 

D. Monoclonal Antibodies Rituximab is a monoclonal antibody to a surface protein in non-Hodgkin s lymphoma cells. It is presently used with conventional anticancer drugs (eg, cyclophosphamide plus vincristine plus prednisone) in low grade lymphomas. Trastuzumab is a monoclonal antibody to a surface protein in breast cancers that overexpress the HER2 protein. Acute toxicity of these antibodies includes nausea and vomiting, chills, fevers, and headache. Rituximab use is associated with hypersensitivity reactions and myelosuppression. Trastuzumab may cause cardiac dysfunction, including congestive heart failure. 

Larsen CG, Thomsen MK, Gesser B, Thomsen PD, Deleuran BW, Nowak J, Skodt V, Thomsen HK, Deleuran M, Thestmp-Pedersen K, et al The delayed-type hypersensitivity reaction is dependent on IL-8. Inhibition of a tuberculin skin reaction by an anti-IL-8 monoclonal antibody. J Immunol 1995 155 2151-2157. 

In contrast, infusion reactions, which are due to the nature of antibody production and structure, represent a class effect of monoclonal antibodies. To address these potentially fatal events, clinical researchers have examined such factors as duration of infusion [164] the role of premedication with antihistamines, acetaminophen, and/or corticosteroids and the molecular etiology of antibody infusion reactions. Infusion reactions may be broadly characterized as cytokine-dependent or hypersensitivity reactions [165]. Cytokine-dependent reactions arise from the interaction of a monoclonal antibody with molecular targets on tumor cells, blood cells, or effector cells, resulting in the release of inflammatory cytokines such as TNF a and interleukin (IL)-6 [166]. In a hypersensitivity reaction, the structure of a monoclonal antibody is recognized as an antigen by the patient s immune system. IgE is produced and... 

Many of these monoclonal antibodies are humanized to prevent the incidence of hypersensitivity reactions that can occur from antibodies from foreign species. 

In a randomized, open, single-center study of two monoclonal antibodies to IL-2 receptors combined with triple immunosuppression (ciclosporin microemulsion, mycophenolate mofetil, and methylpredniso-lone), 212 adult recipients of at least 1HLA-mismatched dead donor renal graft were randomized to induction with basiliximab or daclizumab, given in standard doses. Hospital treatment was required in 50 and 59 patients with infections who received basiliximab and daclizumab respectively. There were one case of renal cell carcinoma and one of basal cell carcinoma in the basiliximab group, and one melanoma in the daclizumab group. There was one hypersensitivity reaction with daclizumab [119 ]. 

The bronchospasm that occurs immediately after aeroallergen inhalation in allergic asthmatic subjects is at least partly an IgE-mediated immediate hypersensitivity reaction (1). At least two lines of evidence support this mechanism for the early asthmatic response. Eirst, pretreatment with an anti-IgE monoclonal antibody attenuates the early phase response in asthmatic subjects (Fig. 1) (2,3). Second, analysis of bronchoalveolar lavage fluid collected immediately after air-... 

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