HLA patterns in patients with nasal polyposis

Luxenberger, Wolfgang; Posch, Ursula; Berghold, Andrea; Hofmann, Thiemo; Lang‐Loidolt, Doris

doi:10.1007/s004050050210

Cited by 53 publications

(36 citation statements)

References 7 publications

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“…At the present time, little is known about the genetics of CRS. While familial aggregation has been observed in genetic epidemiology studies (Cohen et al 2006;Drake-Lee 1992;Greisner and Settipane 1996;Qu et al 2007), few candidate genes have been identiWed (AlShemari et al 2008;Bussu et al 2007;Cheng et al 2006;Fajardo-Dolci et al 2006;Kim et al 2007;Luxenberger et al 2000;Molnar-Gabor et al 2000;Takeuchi et al 2000;Wang et al 2000;Zhai et al 2007). We had initially begun studying the genetics of CRS by utilizing a candidate gene approach (Al-Shemari et al 2008) without a predetermined concept of which areas of the genome to interrogate.…”

Section: Discussionmentioning

confidence: 97%

Identification of susceptibility genes for complex diseases using pooling-based genome-wide association scans

et al. 2009

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The success of genome-wide association studies (GWAS) to identify risk loci of complex diseases is now well-established. One persistent major hurdle is the cost of those studies, which make them beyond the reach of most research groups. Performing GWAS on pools of DNA samples may be an effective strategy to reduce the costs of these studies. In this study, we performed pooling-based GWAS with more than 550,000 SNPs in two case-control cohorts consisting of patients with Type II diabetes (T2DM) and with chronic rhinosinusitis (CRS). In the T2DM study, the results of the pooling experiment were compared to individual genotypes obtained from a previously published GWAS. TCF7L2 and HHEX SNPs associated with T2DM by the traditional GWAS were among the top ranked SNPs in the pooling experiment. This dataset was also used to refine the best strategy to correctly identify SNPs that will remain significant based on individual genotyping. In the CRS study, the top hits from the pooling-based GWAS located within ten kilobases of known genes were validated by individual genotyping of 1,536 SNPs. Forty-one percent (598 out of the 1,457 SNPs that passed quality control) were associated with CRS at a nominal P value of 0.05, confirming the potential of pooling-based GWAS to identify SNPs that differ in allele frequencies between two groups of subjects. Overall, our results demonstrate that a pooling experiment on high-density genotyping arrays can accurately determine the minor allelic frequency as compared to individual genotyping and produce a list of top ranked SNPs that captures genuine allelic differences between a group of cases and controls. The low cost associated with a pooling-based GWAS clearly justifies its use in screening for genetic determinants of complex diseases.

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Section: Discussionmentioning

confidence: 97%

Identification of susceptibility genes for complex diseases using pooling-based genome-wide association scans

et al. 2009

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“…Persistent antigen stimulation has, in fact, been shown to lead to T cell hyporesponsiveness in the setting of several chronic viral infections (Jelley-Gibbs et al 2005;Ahmed and Gray 1996;Letvin and Walker 2003;Feunou et al 2003;Hu et al 1996) and mycobacterial infections (Dagur et al 2010). The possibility of an autoimmune response driving the pathology of nasal polyps may be further supported by evidence of HLA I and HLA II linkages in nasal polyposis (Molnar-Gabor et al 2000;Luxenberger et al 2000;Ramírez-Anguiano et al 2006).…”

Section: Figmentioning

confidence: 97%

Memory T Cells in the Chronic Inflammatory Microenvironment of Nasal Polyposis are Hyporesponsive to Signaling Through the T Cell Receptor

Lehman

Simpson-Abelson

Conway

et al. 2012

JARO

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A majority of T cells from chronic inflammatory tissues derived from patients with nasal polyposis were found to express an effector memory phenotype. We report here that these memory T cells failed to activate NF-κB in response to TCR stimulation but responded normally when the proximal TCR signaling molecules were bypassed with PMA and ionomycin. The dysfunction of these cells was associated with a decrease in the phosphorylation of several TCR proximal signaling molecules including ZAP70, Lck and SLP-76. In addition to the disruption in the TCR signaling pathway, the nasal polyp-associated T cells were shown to have a defect in their ability to translocate LAMP-1 to the cell surface. The results presented here establish that the phenotype and anergy of the T cells in the nasal polyp are similar to those which is seen in memory T cells derived from human tumors and other sites of chronic inflammation.

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“…This observation was supported by Moloney and Olivier [26], showing a linkage between human leukocyte antigen (HLA)-A1 B8 antigen presence and nasal polyps and bronchial asthma prevalence. Also, relatively infrequent fenotype HLA-A74 has been associated with nasal polyps [27], and HLA-DQB1*03 has been shown to be a risk factor for allergic fungal rhinosinusitis and hypertrophic sinus disease; the highest association was found for allergic fungal sinusitis [28]. The recent paper by Fritz et al [29••] suggested an increased expression of mammoglobin gene, which has been mapped to the 11q12.3-13.1.3 region.…”

Section: Family History and Genetic Predispositionmentioning

confidence: 97%

Pathogenesis of nasal polyps: An update

Pawliczak

Lewandowska–Polak

Kowalski

2005

Curr Allergy Asthma Rep

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The cause of nasal polyp formation is still unknown. Genetic predisposition has been suggested, but there are scanty data to support such theories. Activated epithelial cells may be the major source of mediators inducing influx of inflammatory cells (mostly eosinophils) and proliferation and activation of fibroblasts leading to nasal polyp formation. Infectious agents (including viruses, bacteria, or fungi) may be potential primary factors activating nasal epithelial cells. Proinflammatory cytokines and growth factors play important roles in the persistence of mucosal inflammation associated with nasal polyps. Arachidonic acid metabolites seem to be particularly important in the pathogenesis of nasal polyps in patients with aspirin hypersensitivity rhinosinusitis/asthma syndrome.

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HLA patterns in patients with nasal polyposis

Cited by 53 publications

References 7 publications

Identification of susceptibility genes for complex diseases using pooling-based genome-wide association scans

Identification of susceptibility genes for complex diseases using pooling-based genome-wide association scans

Memory T Cells in the Chronic Inflammatory Microenvironment of Nasal Polyposis are Hyporesponsive to Signaling Through the T Cell Receptor

Pathogenesis of nasal polyps: An update

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