<i>Interleukin‐13</i> promoter gene polymorphism ‐1112C/T is associated with the systemic form of mastocytosis

Nedoszytko, Bogusław; Niedoszytko, Marek; Lange, Magdalena; Doormaal, J. van; Gleń, Jolanta; Zabłotna, Monika; Renke, Joanna; Vales, Anja; Buljubasic, F.; Jassem, Ewa; Roszkiewicz, Jadwiga; Valent, Peter

doi:10.1111/j.1398-9995.2008.01827.x

Cited by 31 publications

(25 citation statements)

References 39 publications

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“…This is supported by the fact that sIL-5Rα levels were also correlated with serum IgE levels. In contrast to a recent study describing the association of a polymorphism in the promoter for IL-13 with SM 25 , serum IL-13 levels were not increased in our patients with SM as compared to normal controls (data not shown).…”

Section: Discussioncontrasting

confidence: 99%

IL-5 receptor α levels in patients with marked eosinophilia or mastocytosis

Wilson

Marić

Shukla

et al. 2011

Journal of Allergy and Clinical Immunology

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Background Interleukin (IL)-5 plays a central role in the development and maintenance of eosinophilia and eosinophil activation in a wide variety of eosinophilic disorders. Although IL-5, IL-3 and GM-CSF can modulate expression of IL-5 receptor α (IL-5Rα) on eosinophils in vitro, little is known about soluble and surface IL-5Rα levels in vivo. Objective To assess surface and soluble IL-5Rα levels in patients with eosinophilia and/or mastocytosis. Methods Surface IL-5Rα expression was assessed by flow cytometry in blood and/or bone marrow from subjects with eosinophilia (n=39), systemic mastocytosis (n=8) and normal volunteers (n=28). Soluble IL-5Rα (sIL-5Rα) was measured in a cohort of 177 untreated subjects and correlated with eosinophilia, eosinophil activation, serum tryptase and cytokine levels. Results Whereas IL-5Rα expression on eosinophils inversely correlated with eosinophilia (r=−0.48, p<0.0001), serum levels of sIL-5Rα increased with eosinophil count (r=0.56, p<0.0001), serum IL-5 (r=0.40, p<0.0001) and IL-13 levels (r=0.29, p=0.004). Of interest, sIL-5Rα was significantly elevated in patients with systemic mastocytosis without eosinophilia. Although sIL-5Rα levels correlated with serum tryptase levels in these patients, eosinophil activation, assessed by CD69 expression on eosinophils and serum eosinophil-derived neurotoxin levels, was increased compared to normal subjects. Conclusion These data are consistent with an in vivo IL-5Rα regulatory pathway in human eosinophils similar to that described in vitro and involving a balance between surface and soluble receptor levels. This may have implications with respect to the use of novel therapeutic agents targeting IL-5 and its receptor in patients with eosinophilia and/or mastocytosis.

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Section: Discussioncontrasting

confidence: 99%

IL-5 receptor α levels in patients with marked eosinophilia or mastocytosis

Wilson

Marić

Shukla

et al. 2011

Journal of Allergy and Clinical Immunology

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“…Thus, the differences in gene expression responsible for a neoplastic transformation were not found. The observation of a higher expression of TRAF4 related to Th2 inflammation confirms another observation of the role of the IL-13 gene polymorphism in the pathogenesis of mastocytosis and frequent symptoms of food hypersensitivity affecting this group of patients (Nedoszytko et al 2009). The genetics of anaphylaxis and intolerance are poorly understood.…”

Section: Discussionsupporting

confidence: 83%

The Role of TRAF4 and B3GAT1 Gene Expression in the Food Hypersensitivity and Insect Venom Allergy in Mastocytosis

Górska

Gruchała‐Niedoszytko

Niedoszytko

et al. 2016

Arch. Immunol. Ther. Exp.

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Mastocytosis is an uncommon disease classified as a myeloproliferative neoplasm, however, its symptoms are broad and place patients at crossroads between dermatology, hematology and allergology. Patients with mastocytosis often suffer from symptoms resulting from the activation and release of mediators from the mast cells, such as generalized itching, redness, headache, abdominal cramps, diarrhea, bone pain or arthritis, hypotension and shock. The possible severe, fatal or near fatal reactions caused by food hypersensitivity are reasons for the research focused on marker identification. The aim of the study was to analyse the gene expression differences in mastocytosis patients with and without food and drug hypersensitivity and insect venom allergy (IVA). A total of 57 Caucasian patients with mastocytosis were studied [median age 41.8; range 18–77 years; 15 (26.3 %) males and 42 (73.7 %) females]. Quantitative RT-PCRs of 11 genes plus ribosomal 18S RNA were run. Symptoms of food hypersensitivity were found in 12 patients (21 %), including 3 patients (13 %) with cutaneous mastocytosis (CM), and 9 (28 %) with indolent systemic mastocytosis (ISM). IVA was confirmed in 13 patients (22.8 %) including 6 patients (10.5 %) with CM, and 7 patients (12.3 %) with ISM. Drug hypersensitivity was diagnosed in 10 patients (17.5 %). Significant differences in the gene expression were found for TRAF4 (p = 0.008) in the comparison of the mastocytosis patients with and without concomitant food hypersensitivity. Furthermore significant differences were found in gene expression for B3GAT1 (p = 0.003) in patients with IVA compared to patients without insect sting anaphylaxis in the medical history. The expression of studied genes did not differ according to the presence of drug hypersensitivity. The TRAF4 expression was higher in mastocytosis patients with food hypersensitivity in their medical history, the B3GAT1 expression was lower in mastocytosis patients with IVA in history.

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“…Kit D816V ‐positive SM has been associated with a polymorphism in the IL13 promoter gene (Table ) . This polymorphism leads to a high transcription rate.…”

Section: Genetic Alterations In Patients With Systemic Mcadmentioning

confidence: 99%

Systemic mast cell activation disease: the role of molecular genetic alterations in pathogenesis, heritability and diagnostics

2012

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SummaryDespite increasing understanding of its pathophysiology, the aetiology of systemic mast cell activation disease (MCAD) remains largely unknown. Research has shown that somatic mutations in kinases are necessary for the establishment of a clonal mast cell population, in particular mutations in the tyrosine kinase Kit and in enzymes and receptors with crucial involvement in the regulation of mast cell activity. However, other, as yet undetermined, abnormalities are necessary for the manifestation of clinical disease. The present article reviews molecular genetic research into the identification of disease-associated genes and their mutational alterations. The authors also present novel data on familial systemic MCAD and review the associated literature. Finally, the importance of understanding the molecular basis of inherited mutations in terms of diagnostics and therapy is emphasized.

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Interleukin‐13 promoter gene polymorphism ‐1112C/T is associated with the systemic form of mastocytosis

Abstract: The -1112C/T IL-13 gene polymorphism and the resulting 'hypertranscription' may predispose for the development of SM.

Cited by 31 publications

References 39 publications

IL-5 receptor α levels in patients with marked eosinophilia or mastocytosis

IL-5 receptor α levels in patients with marked eosinophilia or mastocytosis

The Role of TRAF4 and B3GAT1 Gene Expression in the Food Hypersensitivity and Insect Venom Allergy in Mastocytosis

Systemic mast cell activation disease: the role of molecular genetic alterations in pathogenesis, heritability and diagnostics

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