Serum total tryptase levels are increased in patients with active chronic urticaria.

BACKGROUND: We have demonstrated previously mast cell histamine release upon incubation with chronic urticaria (CU) sera, presumably by degranulation. OBJECTIVE: To explore total and mature tryptase in order to assess whether any increase in total tryptase levels is due in part to mast cell degranulation or to mast cell burden. We also wanted to explore differences between the autoimmune groups called idiopathic (serum unable to activate basophils), and to correlate total and mature tryptase levels with different urticaria features. METHODS: We measured total and mature tryptase serum levels in 81 CU patients, 16 atopic donors and 21 healthy control sera. We assessed autoimmunity by measuring the CD63 expression in normal basophil donors upon incubation with CU sera. RESULTS: We found significantly higher levels of total tryptase in the sera of CU patients (6.6 ±4.1 µg/L) than in sera from healthy non-atopic subjects (4.4 ±2.8 µg/L) and from atopic subjects (4.5 ±1.7 µg/L). Mature tryptase levels were undetectable (<1 ng/mL). Total tryptase levels in the autoimmune urticaria group were significantly higher (9.8 ±5.4 µg/L) than the idiopathic urticaria group (4.4 ±2.2 µg/L). A significant difference in total tryptase was found between symptomatic patients (7.3 ±4.1 µg/L) compared with asymptomatic ones (5.7 ±4.1 µg/L) at the time of venesection. No difference was found in mature tryptase levels either. CONCLUSION: Total elevated tryptase levels are not accompanied by an elevated mature tryptase levels, as might be expected if the serum levels reflected mast cell degranulation.

Increased responsiveness of basophils of patients with chronic urticaria to sera but hypo-responsiveness to other stimuli.

BACKGROUND: Although it has been shown that basophils from patients with chronic ordinary urticaria (CU) are less responsive than normal basophils when stimulated with anti-IgE, very few studies have examined the response of those cells to alternative stimuli. OBJECTIVE: To compare releasability between basophils from healthy donors and patients with CU. METHODS: We examined the response of IL-3-treated basophils from healthy donors, atopic controls and CU patients to anti-IgE, monocyte chemoattractant protein-1 (MCP-1), bradykinin, C5a and to sera obtained from other urticaria patients and normal controls. We also compared the response of basophils from CU patients whose sera activate normal basophils (autoimmune CU) from those who do not (idiopathic CU). RESULTS: Basophils of CU patients release significantly less histamine than basophils of normal controls when stimulated with anti-IgE, and to a lesser degree with C5a. No differences were observed when basophils from patients were incubated with Bradykinin or MCP-1. However, when basophils of CU patients were incubated with sera from other CU patients or even normal sera, we found significantly higher histamine release compared with the response of basophils from normal donors. We could not distinguish responsiveness of basophils of patients with chronic autoimmune urticaria from patients with chronic idiopathic urticaria. CONCLUSION: Basophils of patients with chronic idiopathic urticaria and chronic autoimmune urticaria are hypo-responsive to anti-IgE and C5a, normally responsive to MCP-1 or bradykinin, and hyper-responsive to serum. The serum factor to which a response has not yet been identified; however, basophils of patients with chronic urticaria, in general, appear to have abnormal regulation of signaling pathways.

IL3 effect on basophils histamine release upon stimulation with chronic urticaria sera.

BACKGROUND: Chronic urticaria is thought to be an autoimmune disorder in 35-40% of patients because of the presence of an immunoglobulin G (IgG) antibody reactive with the IgE receptor. Patients possessing this antibody are identified by the ability of serum to degranulate donor basophils to release histamine. We questioned whether priming of basophils with interleukin 3 (IL3) would facilitate identification of patients and/or alter the percentage of patients who have a positive assay. METHODS: We incubated 37 chronic urticaria sera with basophils from donors with no urticaria with and without priming with IL3 and compared histamine release in each instance. We also preincubated basophils from a 'non-releaser' with IL3, used these cells to assay chronic urticaria sera, and assessed the contribution of complement. RESULTS: Interleukin 3 increases the amount of histamine release by the sera which is able to activate basophils, but it does not convert negative sera into positive releasers. Interleukin 3 is able to partially reverse 'non-releaser' basophils into cells that respond to chronic urticaria sera, and complement cannot account for the augmentation seen. CONCLUSIONS: Preincubating basophils with IL3 facilitates the identification of sera with anti-IgE receptor antibody but does not affect the percentage of sera designated as positive.