Gene expression profiles in chronic idiopathic (spontaneous) urticaria.

BACKGROUND: The pathophysiology of chronic idiopathic (spontaneous) urticaria (CIU) is poorly understood. OBJECTIVE: We hypothesized that a study of gene expression in active lesions from patients with CIU would uncover unexpected associations. METHODS: We enrolled eight patients with CIU and six healthy controls, and obtained 4 mm punch biopsy specimens of active lesions and unaffected skin of patients with CIU and of skin from normal controls. Routine histologic evaluation was performed, RNA was isolated, and gene expression data were assessed. Due to technical reasons, the final evaluation included six samples of lesional skin, six samples of nonlesional skin, and five samples of normal skin. RESULTS: As expected, lesional skin had more inflammatory cells per high-powered field (mean ± SE, 96 ± 6) than did samples from nonlesional skin of the subjects with CIU (17 ± 2) (p < 0.01). Lesions of CIU showed significant upregulation of 506 genes and reduced expression of 51 genes. Those most upregulated were predominantly involved in cell adhesion (e.g., selectin E [SELE]), cell activation (e.g., CD69), and chemotaxis (e.g., CCL2). Twelve independent canonical pathways with p ≤ 0.001 were identified (including intracellular kinase pathways (RAs-related nuclear protein [RAN] and Janus activated kinase/interferon), cytokine signaling pathways (IL-9, IL10, and IFN), a strong inflammatory response (interferon, IL-9, IL-10, inducible nitric oxide synthase and glucocorticoid pathways) and increased cell proliferation (RAN signaling, cell cycle control, and tRNA charging). CONCLUSIONS: This preliminary study describes a method to study gene activation in urticarial lesions and demonstrated a strong inflammatory response with a large variety of activated genes that are distinct from those reported with other dermatologic conditions.

Allergies to sulfonamide antibiotics and sulfur-containing drugs.

OBJECTIVE: To provide a literature review and clinical summary of the evaluation and management of sulfonamide drug reactions. DATA SOURCES: Published English-language medical literature. STUDY SELECTION: Selected trials of drug desensitization protocols. RESULTS: Obtaining a detailed history is invaluable in assessing a history of reactions to sulfonamide medications, because allergy to these drugs remains a clinical diagnosis at present. Numerous efficacious drug desensitization protocols for management have been published and are reviewed in detail. CONCLUSIONS: The term sulfa allergy is imprecise and misleading and therefore should be discouraged. There are important distinctions between sulfonylarylamines (antimicrobial sulfonamides), nonarylamine (nonantimicrobial) sulfonamides, and sulfones, with regard to allergic and other adverse drug reactions. Most reactions to sulfonylarylamines probably result from multifactorial immunologic and toxic metabolic mechanisms, whereas less is known about the precise mechanisms of reactions to other sulfur-containing drugs.

Urticaria: selected highlights and recent advances.

Urticaria has been called a vexing problem and remains so today. The most important part of the diagnostic evaluation remains a comprehensive and detailed history and physical examination, supplemented with limited laboratory testing. Although acute urticaria has been relatively well understood for some time, significant and important recent advances in under-standing the pathogenesis of chronic urticaria are beginning to provide insight in this challenging field, notably the identification of many of these patients with an autoimmune etiology. Antihistamines of various types continue to represent the keystone of symptomatic treatment, with adjunctive support from medications of other classes, such as antileukotrienes, adrenergics, and immunosuppressive and anti-inflammatory agents (including steroids and cyclosporine). Although some progress has been made at improving symptomatic control of urticaria, further research and discovery are necessary before there can yet be an effective impact on the underlying course and natural history of this condition.

Comparative potency of Ara h 1 and Ara h 2 in immunochemical and functional assays of allergenicity.

To assess the relative potency of the major peanut allergens, Ara h 1 and Ara h 2, we examined the relative ability of purified proteins to bind IgE on immunoblots, to cross-link allergen specific IgE in an in vitro assay of degranulation based on RBL SX-38 cells, and to bind IgE in the ImmunoCap assay. Sera from 12 highly sensitive, peanut allergic patients were studied in all assays. IgE immunoblots with crude peanut extracts showed binding of IgE to multiple bands including the 63 kDa and 17-19 kDa bands that contain Ara h 1 and Ara h 2, respectively. In the functional assay, Ara h 2 was more potent than Ara h 1 in 11 of 12 sera tested with a median potency that was 52.5-fold more than Ara h 1 (P < 0.005). Contrary to findings with the functional assay, IgE immunoblots with purified Ara h 1 and Ara h 2 showed substantially lighter binding of IgE to Ara h 2 compared with Ara h 1 (P = 0.02). The ImmunoCap assay gave intermediate results with slightly more IgE binding to Ara h 2 than to Ara h 1 (P = 0.005). In conclusion, Ara h 2 is a very potent allergen and is much more potent than Ara h 1 for most sera using an in vitro assay of IgE cross-linking and cell activation. This finding is different from what was predicted based on immunoblots or with the ImmunoCap assay.

Urticaria and angioedema: an overview.

Persistent or frequent episodes of urticaria are difficult to evaluate and treat. The best test to identify most patients with a specific underlying cause (eg, physical trigger, allergen, systemic disease) likely is the taking of a careful and detailed history and performance of a physical examination by a specialist who is knowledgeable in urticarial disease. Further study of the pathogenesis and treatment of urticaria is crucial. Given the limited efficacy of presently approved antihistamine treatments and the significant side effects of steroids and cyclosporine, there is a pressing need to evaluate other anecdotally supported urticaria treatments in randomized, controlled trials.

RBL cells expressing human Fc epsilon RI are a sensitive tool for exploring functional IgE-allergen interactions: studies with sera from peanut-sensitive patients.

Rat basophilic leukemia cells (RBL SX-38) express the alpha, beta, and gamma chains of human Fc epsilon RI. Following sensitization with IgE from a subset of allergic human donors, these cells can be triggered by exposure to anti-IgE or to very low concentrations of specific allergens. We examined 18 sera from patients who were highly sensitive to peanuts by history and had anti-peanut IgE by in vitro testing. The ability of these sera to sensitize the RBL SX-38 cells for degranulation with peanut allergens correlates very well with the absolute amount of anti-peanut IgE (r=0.95; p<0.001). The most effective sera contained at least 50 kU/l of total IgE and at least 15 kU/l of peanut-specific IgE. RBL SX-38 cells sensitized with these sera degranulated optimally upon exposure to anti-IgE (net degranulation of 40+/-8%, means+/-S.D.; n=8) and to a 10(5)-10(6) dilution of crude peanut extract (CPE) (37+/-7% net degranulation; 93+/-13% of that seen with anti-IgE). This assay is quite sensitive. Cells sensitized with selected sera are activated by exposure to a 1:10(7) dilution of the CPE containing picogram amounts of peanut allergens. This assay is also quite specific. Cells sensitized with sera from patients with anti-peanut IgE and no detectable IgE against soybean, walnut or grass pollen did not degranulate following exposure to these latter antigens. The converse was also true; cells sensitized with sera from patients without anti-peanut IgE did not react to peanut. These data demonstrate that RBL cells expressing human Fc epsilon RI form the basis of a useful model system for the detection of allergens and for the study of IgE-allergen interactions.