Definitions, Criteria and Global Classification of Mast Cell Disorders with Special Reference to Mast Cell Activation Syndromes: A Consensus Proposal

Activation of tissue mast cells (MCs) and their abnormal growth and accumulation in various organs are typically found in primary MC disorders also referred to as mastocytosis. However, increasing numbers of patients are now being informed that their clinical findings are due to MC activation (MCA) that is neither associated with mastocytosis nor with a defined allergic or inflammatory reaction. In other patients with MCA, MCs appear to be clonal cells, but criteria for diagnosing mastocytosis are not met. A working conference was organized in 2010 with the aim to define criteria for diagnosing MCA and related disorders, and to propose a global unifying classification of all MC disorders and pathologic MC reactions. This classification includes three types of `MCA syndromes' (MCASs), namely primary MCAS, secondary MCAS and idiopathic MCAS. MCA is now defined by robust and generally applicable criteria, including (1) typical clinical symptoms, (2) a substantial transient increase in serum total tryptase level or an increase in other MC-derived mediators, such as histamine or prostaglandin D 2, or their urinary metabolites, and (3) a response of clinical symptoms to agents that attenuate the production or activities of MC mediators. These criteria should assist in the identification and diagnosis of patients with MCAS, and in avoiding misdiagnoses or overinterpretation of clinical symptoms in daily practice. Moreover, the MCAS concept should stimulate research in order to identify and exploit new molecular mechanisms and therapeutic targets. Copyright (C) 2011 S. Karger AG, Base

Nonasthmatic nasal polyposis patients with allergy exhibit greater epithelial MMP positivity

OBJECTIVE: To determine the influence of allergic rhinitis (AR) on the expression of matrix metalloproteinase (MMP)-9, MMP-2, and tissue inhibitor-1 of metalloprotemase (TIMP-1) in nasal polyposis. STUDY DESIGN: A case-control study. SETTING: A tertiary referral center. SUBJECTS AND METHODS: The expression of MMP-9, MMP-2, and TIMP-1 was investigated in the nasal polyp tissue (NP) and maxillary sinus mucosa (MM) samples from 20 AR patients and 20 nonallergic patients undergoing endoscopic sinus surgery. Trichrome, periodic acid-Schiff, and hematoxylin-eosm staining were also performed and those expression levels were compared. RESULTS: Infiltration of eosinophils was shown more intensely in NP rather than in MM, especially in the presence of AR. In the NP of AR patients, increased expression of MMP-9, MMP-2, and TIMP-1 was observed more prominently than in that of the control group. In case of MM, however, there was no significant difference between AR patients and the control group. CONCLUSION: The presence of AR may enhance the expression of MAV-9, MMP-2, and TIMP-1 associated with airway remodeling in nasal polyposis. (C) 2009 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved.YAMAUCHI K, 2009, ALLERGOL INT, V58, P55, DOI 10.2332/allergolint.08-OA-0004Can IH, 2008, OTOLARYNG HEAD NECK, V139, P211, DOI 10.1016/j.otohns.2008.04.032Magnan A, 2008, ALLERGY, V63, P292, DOI 10.1111/j.1398-9995.2007.01584.xBUGDAYCI G, 2008, ACTA HISTOCHEM 1001Nakaya M, 2007, LARYNGOSCOPE, V117, P881, DOI 10.1097/MLG.0b013e318033f9b0Kostamo K, 2007, LARYNGOSCOPE, V117, P638, DOI 10.1097/MLG.0b013e318030aca6Sun HW, 2007, BIOCHEM BIOPH RES CO, V353, P152, DOI 10.1016/j.bbrc.2006.12.002Lim YS, 2007, ANN ALLERG ASTHMA IM, V98, P22Chen YS, 2007, ALLERGY, V62, P66, DOI 10.1111/j.1398-9995.2006.01255.xBhandari A, 2004, ACTA OTO-LARYNGOL, V124, P1165, DOI 10.1080/00016480410017152Bousquet J, 2004, J ALLERGY CLIN IMMUN, V113, P43, DOI 10.1016/j.jaci.2003.09.047Watelet JB, 2004, ALLERGY, V59, P54Shaida A, 2001, J ALLERGY CLIN IMMUN, V108, P791van Toorenenbergen AW, 1999, ALLERGY, V54, P293, DOI 10.1034/j.1398-9995.1999.00028.xSanai A, 1999, ACTA OTO-LARYNGOL, V119, P473Bavbek S, 1996, J INVEST ALLERG CLIN, V6, P172OCONNOR CM, 1994, THORAX, V49, P602

A bispecific antibody against human IgE and human FcgammaRII that inhibits antigen-induced histamine release by human mast cells and basophils

To whom correspondence should be sent. Tam 2 Hal-Pasteur author manuscript pasteur-00271629, version 1 Background: FcγRIIB are low-affinity IgG receptors that we previously demonstrated to negatively regulate IgE-induced mast cell activation when coaggregated with FcεRI. Here, we engineered and characterized a bispecific reagent capable of coaggregating FcγRIIB with FcεRI on human mast cells and basophils. Methods: A bispecific antibody was constructed by chemically crosslinking one Fab ' fragment against human IgE and one Fab ' fragment against human FcγRII. This molecule was used to coaggregate FcεRI with FcγRII on human mast cells and basophils sensitized with human IgE antibodies, and the effect of coaggregation was examined on mediator release upon challenge with specific antigen. Results: When used under these conditions, this bispecific antibody not only failed to trigger the release of histamine by IgE-sensitized cells, but it also prevented specific antigen from triggering histamine release. Comparable inhibitions were observed with mast cells and basophils derived in vitro from cord blood cells and with peripheral blood basophils. Conclusions: The bispecific antibody described here is the prototype of similar molecules that could be used in new therapeutic approaches of allergic diseases based on the coaggregation of activating receptors, such as FcεRI, with inhibitory receptors, such as FcγRIIB, that are constitutively expressed by mast cells and basophils. Key words