Detection of low-molecular-weight mast cell–activating factors in serum from patients with chronic spontaneous urticaria

Background: Functionally active autoantibodies to IgE and to the high-affinity IgE receptor (FcεRI) can be detected in serum in about 40% of patients with chronic spontaneous urticaria (CSU). Recent studies showed that serum from patients with CSU can induce activation of mast cells, irrespective of whether they carry high-affinity IgE receptors. Objective: To evaluate mast cell activation induced by factors in the serum of CSU patients with a molecular weight lower than that of autoantibodies. Methods: Eight CSU patients and 5 healthy controls were evaluated. Whole serum and serum fractionated at 100, 50, and 30 kDa were used to stimulate in vitro LAD2 mast cells. The enzymatic activity of β-hexosaminidase was evaluated in supernatants and cell pellets as a measure of mast cell degranulation. Results: Mean (SEM) release of mast cell β-hexosaminidase induced by whole serum from CSU patients was higher than that induced by serum from the healthy controls (14.4 [2.7%] vs 5.1 [2.4%]; P=.027). In addition, serum fractions below 100 kDa and below 50 kDa from CSU patients induced mast cell degranulation that was significantly higher than that induced by the corresponding fractions in sera from healthy controls (10.2% [1.4%] vs 3.8% [1.9%] [P=.024] and 10.1% [1.2%] vs 3.9% [1.7%] [P=.012], respectively). In 4 CSU patients, we evaluated serum fractions <30 kDa, which retained their capacity to activate mast cells (11.0% [0.7%]). Conclusions: This study shows that sera from CSU patients may contain low-molecular-weight mast cell–activating factors other than autoantibodies. These factors could be an additional mechanism contributing to the pathogenesis of CSU.