Hypersensitivity assessment

Pirmohamed, M., A. Graham, P. Roberts, D. Smith, D. Chadwick, A.M. Breckenridge et al. (1991). Carbamazepine-hypersensitivity Assessment of clinieal and in vitro chemical cross-reactivity with phenytoin and oxcarbazepine. Br. J. Clin. Pharmacol. 32, 741-749. 

Pirmohamed M, Graham A, Roberts P, Smith D, Chadwick D, Breckenridge AM, Park BK (1991) Carbamazepine hypersensitivity assessment of clinical and in vitro chemical cross-reactivity with phenytoin and oxcarbazepine. Br J Clin Pharmacol 32 741-749 Pirmohamed M, Breckenridge AM, Kitteiingham NR, Park BK (1998) Fortnightly review -adverse drug reactions. BMJ 316 1295-1298... 

Franken HH, Dubois AEJ, Minkema HJ, van der Heide S, de Monchy JG Lack of reproducibihty of a single negative sting challenge response in the assessment of anaphylactic risk in patients with suspected yellow jacket hypersensitivity. J Allergy Clin Immunol 1994 93 431-436. 

RCM-related T-cell activity may be assessed in vitro by lymphocyte transformation test [19, 24]. In addition, CD69 upregulation (lymphocyte activation test) was observed in patients with a positive lymphocyte transformation test [24, 39]. These tests appear to be a promising tool to identify drug-reactive T cells in the peripheral blood of patients with RCM-induced drug-hypersensitivity reactions. However, the sensitivity and specificity remain unknown and, therefore, these tests cannot be recommended for routine use yet, but further research on the specificity and sensitivity is indicated. 

The initial antimicrobial regimen should conform to standard guidelines unless an appropriate justification for an alternative regimen is evident. With the first few doses of antimicrobial, assess the patient for hypersensitivity reactions or other acute intolerances. 

Although methods have been established to derive MRLs (Barnes and Dourson 1988 EPA 1990), uncertainties are associated with these techniques. Furthermore, ATSDR acknowledges additional uncertainties inherent in the application of the procedures to derive less than lifetime MRLs. As an example, acute inhalation MRLs may not be protective for health effects that are delayed in development or are acquired following repeated acute insults, such as hypersensitivity reactions, asthma, or chronic bronchitis. As these kinds of health effects data become available and methods to assess levels of significant human exposure improve, these MRLs will be revised. 

Nutrition affects immune status both directly and indirectly. Total lymphocyte count and delayed cutaneous hypersensitivity reactions are immune function tests useful in nutrition assessment. 

Delayed cutaneous hypersensitivity is commonly assessed using antigens to which the patient has been previously sensitized. The recall antigens used most frequently are mumps, Candida albicans, streptokinase-streptodornase, Trichophyton, coccidioidin, and purified protein derivative. Anergy is associated with malnutrition. 

It is important to remember that respiratory sensitization and asthma are related, but not identical, pathologies [31]. Asthma is a specific syndrome which appears to have genetic as well as environmental causes and there are numerous potential triggers which have been identified by immunotoxicologists [32], However, asthma is not the same disease as other respiratory hypersensitivity syndromes (sometimes referred to as chemical asthma, etc.) [33, 34], Various regulatory guidance documents have sought to deal with the latter disease entities to ensure that xenobiotics are assessed appropriately for their ability to induce immune-based pulmonary hypersensitivity reactions [35-37],... 

World Health Organization, International Programme on Chemical Safety, Principles and Methods for Assessing Allergic Hypersensitization Associatedwith Exposure to Chemicals, Environ. Health Criteria 212, Geneva, 1999. 

Holsapple, M.R et al., Assessing the potential to induce respiratory hypersensitivity, Toxicol. Sci., in press. 

Much of the methods development and validation efforts in the past have been focused on evaluation of immunosuppression and contact or dermal sensitization. Currently available animal models and assays are not valid to assess the potential for systemic hypersensitivity and, at this time, reliable models to assess autoimmunity are not available. 

House, R.V., Cytokine measurement techniques for assessing hypersensitivity, Toxicology, 158,51,2001. 

Another question is whether an endpoint reflecting the status of CMI should be included in any DIT protocol.1719 For the measurement of CMI, roundtable participants suggested that a validated DTH or T-cell responses to anti-CD3 be evaluated.38 The DTH assay is considered by the NTP as part of the Tier II test panel.3 Although reports indicate that the delayed-type hypersensitivity (DTH) response can be assessed in weanling rats.41 roundtable participants agreed that data are lacking as to whether cell-mediated immune (CMI) assessments in younger animals are feasible.38 Ultimately, the characterization of a validated endpoint which measures CMI, and the determination of whether such an endpoint should be an essential part of a DIT framework remain critical research needs. 

Griffiths-Johnson, D.A. and Karol, M.H., Validation of a non-invasive technique to assess development of airway hyperreactivity in an animal model of immunologic pulmonary hypersensitivity, Toxicology, 65, 283, 1991. 

Sarlo, K. and Ritz, H.L., Predictive assessment of respiratory sensitizing potential in guinea pigs, in Toxicology of Chemical Respiratory Hypersensitivity, Kimber, I., and Dearman, R.J., Eds., Taylor and Francis, London, pp. 107, 1997. 

There are no established assays that reliably assess potential for autoimmunity and acute systemic hypersensitivity. The popliteal lymph node assay (PLNA) has only a relatively small database available for assessing its usefulness for drug regulatory purposes. 

Types II and III Hypersensitivity. No simple animal models are currently available to assess Type II (antibody-mediated cytotoxicity) hypersensitivity reactions. IgE antibodies and immune complexes in the sera of exposed animals can be assayed using ELISA or RIA techniques that require the use of specific antibodies to the drug. 

Type IV Hypersensitivity. There are several well-established preclinical models for assessing Type IV (delayed-type) hypersensitivity reactions following dermal exposure, but not for predicting this response after systemic exposure. 

Type IV hypersensitivity responses are elicited by T lymphocytes and are controlled by accessory cells and suppressor T cells. Macrophages are also involved in that they secrete several monokines, which results in proliferation and differentiation of T cells. Thus, there are numerous points along this intricate pathway in which drugs may modulate the final response. To achieve a Type IV response, an initial high-dose exposure or repeated lower-dose exposures are applied to the skin the antigen is carried from the skin by Langerhans cells and presented to cells in the thymus to initiate T-cell proliferation and sensitization. Once sensitized, a second challenge dose will elicit an inflammatory response. Thus, before sensitivity can be assessed, each of the models used to evaluate dermal hypersensitivity requires as a minimum ... 

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