Allergy proceedings : the official journal of regional and state allergy societies最新文献

Allergy resulting from exposure to latex proteins has been reported with increasing frequency in certain patient and occupational groups. Patients with latex allergy demonstrate cross-reactivity with some food allergens. Although amino acid homology of a few polypeptides from food and latex have been reported, no information is available comparing food and latex allergens. In the present study, we have obtained antibody from latex-sensitive patients by affinity absorption with various food and latex allergen extracts. The antibodies were then evaluated for reactivity with various antigens by ELISA. The results indicated that IgE cross-reactivity existed between different latex and food antigens. Hence, care should be exercised during evaluation of patients, as the clinical response may not be directed to the primary sensitizing antigen and may represent cross-reactivity of antigens.

The growing recognition of asthma as an immunologic disease mediated by inflammatory cells and mediators has changed the nature of therapy and monitoring of this disease. Modulation of inflammatory mediators such as leukotrienes, prostaglandins, and adenosine by specific immunoregulatory pharmacotherapy is now becoming well-recognized as essential for proper management of allergic diseases, including asthma. The newly-developed immunoassays for specific inflammatory cell activation markers, such as tryptase for mast cell activation, myeloperoxidase for neutrophil activation, and eosinophilic cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) for eosinophil activation, may significantly enhance the ability to both determine the cellular etiology of allergic inflammation and also to monitor the efficacy of antiinflammatory therapies in suppressing cell-specific immunologic events.

Earlier studies of adenosine as a modulator of mast cell secretory functions have demonstrated that addition of exogenous adenosine to rat peritoneal mast cells has appeared to be a pro-inflammatory molecule in allergic reactions. More recent investigative studies with mouse bone-marrow mast cells have confirmed the role of adenosine as a potent augmenter of mast cell mediator release. Ongoing investigation is centered on characterization of an adenosine subtype in mast cells and biochemical mechanisms by which adenosine may effect bronchoconstrictor response in allergen-sensitive individuals.

Previous immunosuppressive agents utilized as therapies for immune system mediated diseases such as chronic allergic asthma, and rheumatoid arthritis include purine antagonists, methotrexate, and gold salts. These treatment modalities have been shown to elicit either limited treatment efficacy or to produce undesirable side effects in many individuals. Cyclosporin A is a potent immunosuppressive agent which appears to arrest division of T lymphocytes and inhibit mediator release from mast cells. However, like other immunosuppressive agents, cyclosporin A may also produce many potentially serious side effects; among these is the possibility of irreversible renal damage. Nephrotoxicity can be attenuated, because renal pathological changes seem to be high cumulative dose-related. If whole blood levels of cyclosporin A are maintained between 200 and 500 ng/mL, serious renal toxicity is unusual. Investigation of cyclosporin A in individuals who have severe long-term corticosteroid-dependent chronic asthma has demonstrated the efficacy of this agent, resulting in clinically significant improvement in pulmonary function. Therefore, it can be hypothesized that T lymphocytes may act as effector cells in cell-mediated hypersensitivity reactions in atopic allergic inflammation.

It had been postulated from earlier studies that platelets of aspirin-sensitive asthmatics reacted to aspirin and other cyclo-oxygenase inhibitors. Similarly, a generalized abnormality had been suggested in the regulation of arachidonic acid oxidative pathways in blood leukocytes of patients with aspirin-induced asthma. Studies of activation in vitro as well as in vivo assessment of polymorphonuclear leukocytes have not been conclusive of metabolic pathways inducing bronchospasm in aspirin-sensitive asthmatic patients. Serum levels of tryptase, a specific marker of mast cell activation, appear to increase during bronchoconstriction following ingestion of oral aspirin. Eosinophil cationic protein (ECP) levels in serum are concomitantly elevated. Leukotriene antagonists may partially protect individuals with allergen-provoked or aspirin-provoked bronchoconstriction.

Mast cells and basophils are implicated as major effector cells in allergic disease. However, both mast cell and basophil involvement in clinical events have been difficult to assess heretofore because of localization of mast cells in tissues and the small numbers of basophils in the circulatory system. Tryptase has been found to be a discriminating marker for the participation of human mast cells in immediate allergic responses, and therefore provides precise assessment of mast cell activation. High tryptase levels in serum, plasma, and other biologic fluids are consistent with mast cell activation in systemic anaphylaxis and other immediate hypersensitivity allergic reactions. Although basophil activation has been implicated in late phase response to allergen challenge, sensitive specific indicators of basophil activation are still under investigation.

Studies suggest that leukotrienes which have been metabolized from arachidonic acid released from membranes phospholipids during cell activation may play a significant role in a variety of inflammatory disorders including the pathophysiology of chronic allergic asthma. Two major types of polyunsaturated fatty acids prominent in marine fish oils are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DCHA). These fish oils limit leukotriene synthesis and biological activities by substituting substrate fatty acids as alternatives to arachidonic acid. Both EPA and DCHA inhibit the conversion of arachidonic acid by the cyclooxygenase pathway to prostanoid metabolites and reduce the production of platelet-activating factor (PAF).

Eosinophil cationic proteins (ECP), eosinophil protein X (EPX), eosinophil peroxidase (EPO), eosinophil-derived neurotoxin (EDN), and the major basic protein (MBP) have been identified as potent cytotoxic secretory proteins in degranulated eosinophils. Studies of these proteins have clearly indicated a role for eosinophil-derived proteins in inflammatory diseases, including asthmatic inflammation. It has been shown that higher levels of ECP in asthmatics were concomitant with severity of the disease and related to efficacy of treatment of asthma. Proper handling of blood serum for measurement of eosinophil and neutrophil markers including myeloperoxidase (MPO) is essential. Moreover, the time factor in ECP measurement is an important variable because ECP levels differ in chronic stable asthma, during acute exacerbations of asthma, and after allergen challenge. Simultaneous measurements of ECP and MPO may prove to be useful in determining various causes of asthma exacerbations, helping to discriminate between allergic etiologies wherein ECP levels may increase versus infectious etiologies wherein MPO levels may increase. Monitoring the efficacy of anti-inflammatory therapies such as corticosteroids may be enhanced by serial determinations of ECP levels in the blood.

Sensitization to environmental allergens in nasal polyposis was evaluated in an in vitro study conducted on 90 patients undergoing polypectomy by measuring total and specific IgE for a panel of common allergens and levels of IgG, IgA and albumin in serum, and nasal secretions (NSe). Fifty healthy individuals were chosen as a control group. Total IgE concentrations were higher in patients with nasal polyps than in controls. RAST was positive in serum in 34 (38%), in NSe in 29 (32%), and exclusively in NSe in 10 patients (11%). Allergens most frequently involved were mites and cat dander. No differences were found between the study and control groups for serum and NSe IgA, albumin, and serum IgG, whereas IgG in NSe were significantly higher in patients with nasal polyps. Subjects with positive RAST only in NSe had significantly lower secretory IgA than did controls. Our data indicate that in nasal polyposis: 1) sensitization to aeroallergens is relatively common; 2) a local production of specific IgE may occur, especially for perennial allergens; 3) prolonged exposure to these allergens gives rise to chronic nasal inflammation, with altered local production of immunoglobulins.