집먼지진드기에 감작된 알레르기성 천식과 비염 환자에서 기도 염증 정도의 예측 인자로서의 혈청 c-kit 수용체의 역할
The Role of C-Kit Receptor Level as a Serological Marker for Predicting the Extent of Upper and Lower Airway Inflammation in Patients Sensitized to House Dust Mites
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Background: Allergic rhinitis can progress to asthma. Both allergic rhinitis and asthma are characterized by Th2-dependent inflammation due to activated mast cells and eosinophils. Mast cells are dependent on kit-mediated activation, and the stem cell factor (SCF)/c-kit pathway leads to eosinophil infiltration. We investigated whether inflammation through the SCF/c-kit pathway would be associated with upper and lower airway inflammation. Methods: We enrolled 71 allergic asthma patients with rhinitis (group I) and 47 patients with allergic rhinitis alone (group II), and 59 non-atopic healthy controls (group III). Groups I and II showed positive responses to house dust mites in skin prick tests. The serum concentrations of c-kit receptor and SCF were measured by using ELISA. Eosinophil cationic protein (ECP) levels were measured by using the CAP system. Other clinical parameters were analyzed. Results: There were significant differences in the mean values of c-kit receptor levels between the 3 groups (117.27± 41.05 vs. 93.13±37.21 vs. 88.45±24.32 ng/mL, P<0.001). The c-kit receptor level was the highest in group I. However, no significant differences were found in SCF levels between the 3 groups. A positive correlation was found between c-kit receptor and ECP levels in groups I and II (r=0.31, P=0.016). Moreover, a positive correlation was found between c-kit receptor levels and total eosinophil counts in groups I and II (r=0.34, P<0.001). However, there were no significant associations between c-kit receptor levels and clinical parameters, such as forced expiratory volume 1% predicted value in group I. Conclusion: Serum c-kit receptor levels can be a useful serologic marker for predicting the extent of eosinophilic inflammation in upper and lower airway inflammation.
Abstract
Background: Allergic rhinitis can progress to asthma. Both allergic rhinitis and asthma are characterized by Th2-dependent inflammation due to activated mast cells and eosinophils. Mast cells are dependent on kit-mediated activation, and the stem cell factor (SCF)/c-kit pathway leads to eosinophil infiltration. We investigated whether inflammation through the SCF/c-kit pathway would be associated with upper and lower airway inflammation. Methods: We enrolled 71 allergic asthma patients with rhinitis (group I) and 47 patients with allergic rhinitis alone (group II), and 59 non-atopic healthy controls (group III). Groups I and II showed positive responses to house dust mites in skin prick tests. The serum concentrations of c-kit receptor and SCF were measured by using ELISA. Eosinophil cationic protein (ECP) levels were measured by using the CAP system. Other clinical parameters were analyzed. Results: There were significant differences in the mean values of c-kit receptor levels between the 3 groups (117.27± 41.05 vs. 93.13±37.21 vs. 88.45±24.32 ng/mL, P<0.001). The c-kit receptor level was the highest in group I. However, no significant differences were found in SCF levels between the 3 groups. A positive correlation was found between c-kit receptor and ECP levels in groups I and II (r=0.31, P=0.016). Moreover, a positive correlation was found between c-kit receptor levels and total eosinophil counts in groups I and II (r=0.34, P<0.001). However, there were no significant associations between c-kit receptor levels and clinical parameters, such as forced expiratory volume 1% predicted value in group I. Conclusion: Serum c-kit receptor levels can be a useful serologic marker for predicting the extent of eosinophilic inflammation in upper and lower airway inflammation.
참고문헌 (40)
- Bousquet J, "World Health Organization; GA(2)LEN; AllerGen. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen)", Allergy, 63(86), pp.8~160 (2008)
- Bousquet J, "Asthma. From bronchoconstriction to airways inflammation and remodeling", Am J Respir Crit Care Med, 161, pp.1720~1745 (2000)
- Guerra S, "Rhinitis as an independent risk factor for adult-onset asthma", J Allergy Clin Immunol, 109, pp.419~425 (2002)
- Linneberg A, "The link between allergic rhinitis and allergic asthma: a prospective population-based study. The Copenhagen Allergy Study", Allergy, 57, pp.1048~1052 (2002)
- Annesi-Maesano I., "Epidemiological evidence of the occurrence of rhinitis and sinusitis in asthmatics", Allergy, 54(57), pp.7~13 (1999)
- Sibbald B, "Epidemiology of seasonal and perennial rhinitis: clinical presentation and medical history", Thorax, 46, pp.895~901 (1991)
- Leynaert B, "Perennial rhinitis: an independent risk factor for asthma in nonatopic subjects: results from the European Community Respiratory Health Survey", J Allergy Clin Immunol, 104, pp.301~304 (1999)
- Townley RG, "Bronchial sensitivity to methacholine in current and former asthmatic and allergic rhinitis patients and control subjects", J Allergy Clin Immunol, 56, pp.429~442 (1975)
- Frew AJ, "Sublingual immunotherapy", N Engl J Med, 358, pp.2259~2264 (2008)
- Strunk RC, "Omalizumab for asthma", N Engl J Med, 354, pp.2689~2695 (2006)
- Schleimer RP, "Role of human basophils and mast cells in the pathogenesis of allergic diseases", J Allergy Clin Immunol, 76, pp.369~374 (1985)
- Huang E, "The hematopoietic growth factor KL is encoded by the Sl locus and is the ligand of the c-kit receptor, the gene product of the W locus", Cell, 63, pp.225~233 (1990)
- Zsebo KM, "Stem cell factor is encoded at the Sl locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor", Cell, 63, pp.213~224 (1990)
- Langley KE, "Soluble stem cell factor in human serum", Blood, 81, pp.656~660 (1993)
- Chabot B, "The proto-oncogene c-kit encoding a transmembrane tyrosine kinase receptor maps to the mouse W locus", Nature, 335, pp.88~89 (1988)
- Yuan Q, "Human peripheral blood eosinophils express a functional c-kit receptor for stem cell factor that stimulates very late antigen 4 (VLA-4)- mediated cell adhesion to fibronectin and vascular cell adhesion molecule 1 (VCAM-1)", J Exp Med, 186, pp.313~323 (1997)
- Oliveira SH, "Stem cell factor induces eosinophil activation and degranulation: mediator release and gene array analysis", Blood, 100, pp.4291~4297 (2002)
- Nilsson G, "Stem cell factor is a chemotactic factor for human mast cells", J Immunol, 153, pp.3717~3723 (1994)
- Bischoff SC, "c-kit ligand: a unique potentiator of mediator release by human lung mast cells", J Exp Med, 175, pp.237~244 (1992)
- Al-Muhsen SZ, "The expression of stem cell factor and c-kit receptor in human asthmatic airways", Clin Exp Allergy, 34, pp.911~916 (2004)
- Lei Z, "SCF and IL-31 rather than IL-17 and BAFF are potential indicators in patients with allergic asthma", Allergy, 63, pp.327~332 (2008)
- 민양기, "알레르기성 비염 마우스에서 Stem Cell Factor의 비강내 투여 효과", 대한이비인후과학회지 두경부외과학, 46(2), pp.110~114 (2003), 대한이비인후과학회
- Grossman J, "One airway, one disease", Chest, 111, pp.11S~16S (1997)
- Brozek JL, "Grading of Recommendations Assessment, Development and Evaluation Working Group. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 revision", J Allergy Clin Immunol, 126, pp.466~476 (2010)
- Galli SJ, "The development of allergic inflammation", Nature, 454, pp.445~454 (2008)
- Poston RN, "Immunohistochemical characterization of the cellular infiltration in asthmatic bronchi", Am Rev Respir Dis, 145, pp.918~921 (1992)
- Kim CK, "Bronchoalveolar lavage cytokine profiles in acute asthma and acute bronchiolitis", J Allergy Clin Immunol, 112, pp.64~71 (2003)
- Howarth PH, "Allergic rhinitis: not purely a histamine-related disease", Allergy, 55(64), pp.7~16 (2000)
- Bentley AM, "Immunohistology of the nasal mucosa in seasonal allergic rhinitis: increases in activated eosinophils and epithelial mast cells", J Allergy Clin Immunol, 89, pp.877~883 (1992)
- Yoon JH, "Ultrastructure of the nasal mucosal epithelium in perennial allergic rhinitis", Korean J Otolaryngol, 33, pp.472~481 (1990)
- Asquith KL, "The IL-3", IL-5, J Immunol, pp.2008, 180[DOI]
- Kim YK, "Stem cell factor in nasal polyposis and allergic rhinitis: increased expression by structural cells is suppressed by in vivo topical corticosteroids", J Allergy Clin Immunol, 100, pp.389~399 (1997)
- Kowalski ML, "Association of stem cell factor expression in nasal polyp epithelial cells with aspirin sensitivity and asthma", Allergy, 60, pp.631~637 (2005)
- Kanbe T, "Serum levels of soluble stem cell factor and soluble KIT are elevated in patients with atopic dermatitis and correlate with the disease severity", Br J Dermatol, 144, pp.1148~1153 (2001)
- Otsuka H, "Stem cell factor mRNA expression and production in human nasal epithelial cells: contribution to the accumulation of mast cells in the nasal epithelium of allergy", J Allergy Clin Immunol, 102, pp.757~764 (1998)
- Da Silva CA, "Effect of glucocorticoids on stem cell factor expression in human asthmatic bronchi", Clin Exp Allergy, 36, pp.317~324 (2006)
- Makowska JS, "Stem cell factor and its soluble receptor (c-kit) in serum of asthmatic patients- correlation with disease severity", BMC Pulm Med, 9, pp.27~ (2009)
- 박도심, "지속성 알레르기비염 환자에서 혈액 내 IL-31, Stem Cell Factor, B Cell-Activating Factor 농도", Journal of Rhinology, 16(1), pp.31~34 (2009), 대한비과학회
- Eechoute K, "Suppressing effects of sunitinib on allergic rhini tis: previously undefined side effects with therapeutic potential", J Clin Pharmacol, 51, pp.1592~1595 (2011)
- Humbert M, "Masitinib, a c-kit", PDGF receptor tyrosine kinase inhibitor, improves disease control in severe corticosteroid-dependent asthmatics, 2009, pp.64, 1194~1201
