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TRANSCRIPT
J ALLERGY CLIN IMMUNOL
FEBRUARY 2013
AB116 Abstracts
SUNDAY
420 Aspirin Augments IgE-Mediated Histamine Release FromHuman Peripheral Basophils Via Syk Kinase Activation
Hiroaki Matsuo1, Tomoharu Yokooji1, Hironobu Morita1, Mina Ooi1,
Kana Urata1, Shunsuke Takahagi2, Kaori Ishii2, Yuhki Yanase2, Takaaki
Hiragun2, Shoji Mihara2, Michihiro Hide2; 1Department of Pathophysiol-
ogy and Therapeutics, Graduate School of Biomedical and Health
Sciences, Hiroshima University, Hiroshima, Japan, 2Department of
Dermatology, Graduate School of Biomedical and Health Sciences,
Hiroshima University, Hiroshima, Japan.
RATIONALE: Non-steroidal anti-inflammatory drugs (NSAIDs), espe-
cially aspirin, and food additives (FAs) may exacerbate allergic symptoms
in patients with chronic idiopathic urticaria and food-dependent exercise-
induced anaphylaxis (FDEIA). Augmentation of histamine release from
human mast cells and basophils by those substances is speculated to be the
cause of exacerbated allergic symptoms. We sought to investigate the
mechanism of action of aspirin on IgE-mediated histamine release.
METHODS: The effects of NSAIDs, FAs or cyclooxygenase (COX)
inhibitors on histamine release from human basophils concentrated by
gravity separation were evaluated. The phosphorylation of Syk kinase was
detected with anti-phospho-Syk antibodies.
RESULTS: Benzoate and tartrazine, which have no COX inhibitory
activity, augmented histamine release from basophils similar to aspirin. In
contrast, ibuprofen, meloxicam, FR122047 and NS-398, which have COX
inhibitory activity, did not affect histamine release. These results indicate
that the augmentation of histamine release by aspirin is not due to COX
inhibition. It was observed that aspirin augmented histamine release from
human basophils only when specifically activated by anti-IgE antibodies,
but not by A23187 or formyl-methionyl-leucyl-phenylalanine. When the
IgE receptor signaling pathway was activated, aspirin increased the
phosphorylation of Syk. Moreover, patients with chronic urticaria and
FDEIA tended to be more sensitive to aspirin as regards the augmentation
of histamine release, compared with healthy controls.
CONCLUSIONS: Aspirin enhanced histamine release from basophils via
increased Syk kinase activation, and that the augmentation of histamine
release by NSAIDs or FAs may be one possible cause of worsening
symptoms in patients with chronic urticaria and FDEIA.
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421422 Genetic Variation of the Histamine Pathway in Subjects withAsthma
Nikita Raje, MD, MBBS1,2, Carrie A. Vyhlidal, PhD1, Amanda K.
Riffel1, Hongying Dai, PhD1, Bridgette L. Jones, MD FAAAAI1;1Children’s Mercy Hospital & Clinics, Kansas City, MO, 2University of
Missouri- Kansas City.
RATIONALE: Histamine is known to be an important mediator in the
pathophysiology of asthma.We have previously reported thatHRH1 is dif-
ferentially expressed in subjects with asthma relative to those without
asthma. Genetic variations in the pathway responsible for histamine pro-
duction, response, and degradation have been observed to be related to
the disease. We aimed to determine if single nucleotide polymorphisms
(SNPs) in genes involved in the histamine pathway were associated with
diagnosis of asthma and/or mRNA expression of HRH1.
METHODS: We enrolled children and adults (n594) with and without
asthma who met inclusion/exclusion criteria. HRH1 expression was deter-mined by qRT-PCR on mRNA. Genotyping was performed by real time
PCR for known SNPs (n510) in HDC, HRH1, HRH4, HNMT and ABP1.
Linear regression analysis, Fisher’s Exact test and Chi square test were
used to determine differences in genotype for gene expression and asthma
diagnosis with significance determined by p<0.05.
RESULTS: No difference was observed for genotype among the 10 SNPs
tested between subjects with andwithout asthma. Subjects who possessed a
T allele at ABP1 995 exhibited higher expression of HRH1 (14.1 CT, 15
TT) relative to those homozygous for the major allele (12.7 CC), (p value
0.037).
CONCLUSIONS: SNPs tested within genes along the histamine pathway
do not appear to be associated with a diagnosis of asthma in our study
population. Presence of a T allele at ABP1 995 may result in increased ex-
pression ofHRH1. Further studies are needed to determine the potential bi-
ological and clinical significance of this finding.
423 The Mastocytosis Society Survey On Mast Cell Disorders:Patient Experiences and Perceptions
Susan Jennings1, Nancy C. Russell1, Blair Jennings1, Valerie Slee1, Lisa
Sterling1, Mariana C. Castells, MD PhD FAAAAI2, Peter Valent3, Cem
Akin, MD PhD FAAAAI2; 1The Mastocytosis Society, Hastings, NE,2Brigham and Women’s Hospital, Harvard Medical School, Boston,
MA, 3Medical University of Vienna, Vienna, Austria.
RATIONALE: Mast cell diseases include mastocytosis and mast cell
activation syndromes, some of which have been shown to involve clonal
defects in mast cells that result in abnormal cellular proliferation or
activation. Numerous clinical studies of mastocytosis have been published,
but no population based comprehensive surveys of patients in the United
States (U.S.) have been identified. Few mast cell disease specialty centers
exist in the U.S. and awareness of these mast cell disorders is limited
among non-specialists. Accordingly, information concerning the experi-
ences of the overall estimated population of these patients has been
lacking. In order to identify the experiences and perceptions of patients
with mastocytosis, mast cell activation syndrome and related disorders,
The Mastocytosis Society, a U.S. based patient advocacy, research and
education organization, conducted a survey of its members and other
people known or suspected to be part of this patient population.
METHODS: Aweb-based survey was publicized through clinics treating
such patients and the Society’s newsletter, Web site and online blogs. Both
online and paper copies of the questionnaire were provided, together with
required statements of consent.
RESULTS: The first results are presented for 420 patients. These results
include demographics, diagnoses, symptoms, allergies, triggers of mast
cell symptoms, and disease impact.
CONCLUSIONS: Patients with mastocytosis and mast cell activation
syndromes have provided clinical specialists, collaborators, and other
patients with information to enable them to explore and deepen their
understanding of the experiences and perceptions of people coping with
these disorders.