Detection of Low-Molecular-Weight Mast Cell–Activating Factors in Serum From Patients With Chronic Spontaneous Urticaria
Cugno M1, Tedeschi A2, Frossi B3, Bossi F4, Marzano AV5, Asero R6
1Medicina Interna, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di
Milano, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milano, Italy
2SC Medicina Interna a Indirizzo Pneumologico, AO Fatebenefratelli e Oftalmico, Milano, Italy
3Dipartmento di Scienze e Tecnologie Biomediche, Università di Udine, Udine, Italy
4Dipartmento di Scienze Mediche, Chirurgiche e della Salute, Università di Trieste, Ospedale Universitario di
Cattinara, Trieste, Italy
5Unità Operativa di Dermatologia, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università
degli Studi di Milano, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milano, Italy
6Ambulatorio di Allergologia, Clinica San Carlo, Paderno Dugnano, Italy
J Investig Allergol Clin Immunol 2016; Vol 26(5)
Background y Objective: 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. 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.
Key words: Chronic urticaria, Pathogenesis, Histamine-releasing factors, Mast cells.