Chengshuo Wang

Genetic association study of FOXP3 polymorphisms in allergic rhinitis in a Chinese population.

The FOXP3 gene encodes a transcription factor thought to be essential for the development and function of regulatory T cells, which are prevailing mediators of immunological tolerance via suppression/modulation of both T helper (Th)-1 and Th-2 mediated immune responses. Previous studies have demonstrated an association between common polymorphisms in FOXP3 and a number of immune diseases. The aim of this study was to investigate whether genetic polymorphisms at the FOXP3 locus predispose to allergic rhinitis (AR) in a Chinese Han population. Six polymorphisms in promoter and intron areas were genotyped in 193 AR subjects and 191 healthy controls. Twelve exons were also analyzed among cohorts of 157 AR patients and 118 healthy controls. Whole-population and gender strata analyses revealed that no single nucleotide polymorphisms in FOXP3 were identified as significantly associated with AR. Regarding the stratified analysis for heterozygotes and homozygotes, the heterozygous allele in rs3761548 (p = 0.020, OR(Het) = 3.12) appeared significant. Subgroup analysis for the presence of different allergen allergies also demonstrated a significant association for house dust mites (rs3060515, p = 0.010, odds ratio (OR) = 2.18; rs3761547, p = 0.013, OR = 2.00). Additionally, no polymorphisms in coding regions contributing to a susceptibility to AR were noted. Our study provides the first evidence for the association of the FOXP3 polymorphism with AR in a Chinese population.

Allergen-specific IL-10-secreting type I T regulatory cells, but not CD4(+)CD25(+)Foxp3(+) T cells, are decreased in peripheral blood of patients with persistent allergic rhinitis.

We investigate the frequencies of CD4(+)CD25(+)Foxp3(+) T cells and allergen-specific IL-10(+)IL-4(-), IFN-gamma(+)IL-4(-), IL-4(+)IFN-gamma(-)CD4(+) T cells (which display characteristics of nTreg, Tr1-, Th1- and Th2- cells, respectively) in peripheral blood mononuclear cells (PBMCs) of patients with AR and of healthy individuals. In addition, we estimated the suppressive effect of CD4(+)CD25(+) Treg cells and allergen-specific, IL-10-secreting cells from both two groups. The frequency of CD4(+)CD25(+)Foxp3(+) T cells is similar in 43 AR patients compared with 38 healthy subjects. CD4(+)CD25(high) cells retain suppressive activity on allergen-stimulated cell proliferation and cytokine production of Th1 but not Th2 cells in both groups. However, the frequency of allergen-specific IL-10(+)IL-4(-)CD4(+) T cells is reduced in AR patients, and correlates inversely to clinical symptom scores. Allergen-specific, IL-10-secreting cells potently suppressed D. pteronyssinus major allergen 1-stimulated cell proliferation and cytokine production (IFN-gamma and IL-4) in healthy individuals. Altogether our data indicate that the number and function of CD4(+)CD25(+) Treg cells from allergic patients are not impaired. However, the deficiency of allergen-specific Tr1 cells may play a role in the development of AR.

Comparative study of cluster and conventional immunotherapy schedules with dermatophagoides pteronyssinus in the treatment of persistent allergic rhinitis.

Background and Objectives: Allergy to house dust mite is one of the most common causes of allergic rhinitis (AR) in China. We sought to compare the efficacy and safety of a 6-week cluster schedule of specific immunotherapy with that of a 14-week conventional schedule for the treatment of subjects with persistent AR. Methods: The trial was a prospective and randomized study involving 96 patients with persistent AR, aged 14–60 years, who were allergic to Dermatophagoides pteronyssinus. While 48 patients were randomly assigned to the cluster schedule reaching the maintenance dose within 6 weeks, the other 48 were randomly assigned to the conventional schedule reaching the maintenance dose within 14 weeks. Eighty-nine patients completed a 1-year treatment course. While kinetic changes in clinical efficacy and adverse reactions were observed during the treatment, quality of life, cutaneous reactivity and serum-specific immunoglobulin E to Dermatophagoides pteronyssinus were measured before and after treatment. Results: The cluster schedule reduced the time to reach the maintenance dose by 57% and caused mild systemic adverse reactions after 1.0% of injections (6.7% of patients), with no differences in comparison with the conventional schedule. Cluster specific immunotherapy led to decreases in clinical symptoms and earlier use of medication than did the conventional schedule. Similar improvements in quality of life and reduced cutaneous reactivity without significant changes in specific immunoglobulin E were observed in both groups after 1 year. Conclusions: The cluster schedule is a safe alternative to the conventional schedule with the advantage of achieving clinical effectiveness sooner.

Responses of CD4(+) CD25(+) Foxp3(+) and IL-10-secreting type I T regulatory cells to cluster-specific immunotherapy for allergic rhinitis in children.

To cite this article: Lou W, Wang C, Wang Y, Han D, Zhang L. Responses of CD4+CD25+Foxp3+ and IL‐10‐secreting type I T regulatory cells to cluster‐specific immunotherapy for allergic rhinitis in children. Pediatric Allergy Immunology 2011: doi: 10.1111/j.1399‐3038.2011.01249.x.

Predictive significance of tissue eosinophilia for nasal polyp recurrence in the Chinese population.

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) remains a challenging clinical entity with its propensity for recurrence. Tissue eosinophilia is a hallmark of CRSwNP, and its role in polyp recurrence is a subject of much investigation. Objective The aim of this study was to evaluate the association between clinical parameters, especially tissue eosinophilia and polyp recurrence, and to identify the optimal cutoff value of tissue eosinophilia as a predictor for polyp recurrence in Chinese subjects. Methods Overall, 387 patients with CRSwNP were enrolled in this retrospective analysis and postoperative follow-up for polyp recurrence was over a period that lasted >24 months (mean [standard deviation], 34.03 ± 4.95 months). The baseline demographic and clinical features and the preoperative computed tomography were compared, and mucosal specimens obtained at endoscopic sinus surgery were assessed for inflammatory cells by using histocytologic staining. Predictive factors associated with polyp recurrence were analyzed by logistic regression analysis, and optimal cutoff points of the predictors were determined by receiver operating characteristic curves and the Youden index. Results A total of 55.3% patients (214β87) experienced recurrence. Tissue eosinophilia markedly outweighed other parameters and correlated with polyp recurrence. Receiver operating characteristic curves indicated that a cutoff value of 27% tissue eosinophils predicted recurrence with 96.7% sensitivity and 92.5% specificity (area under the curve = 0.969; p < 0.001); and an absolute count of 55 eosinophils per high power field predicted recurrence with 87.4% sensitivity and 97.1% specificity (area under the curve = 0.969; p < 0.001). Conclusion A tissue eosinophil proportion of >27% of total cells or a tissue eosinophil absolute count of >55 eosinophils per high power field may act as a reliable prognostic indicator for nasal polyp recurrence within 2 years after surgery.

An increased prevalence of self-reported allergic rhinitis in major Chinese cities from 2005 to 2011

The prevalence of allergic rhinitis (AR) has increased worldwide in recent decades. This study was conducted to investigate the prevalence of self‐reported AR and profiles of AR‐related comorbidities in the adult population of China over time.

Biofilm formation and Toll-like receptor 2, Toll-like receptor 4, and NF-kappaB expression in sinus tissues of patients with chronic rhinosinusitis.

Background Bacterial biofilm formation is associated with chronic rhinosinusitis (CRS). However, how bacterial biofilms are related to innate immune response in patients is poorly understood. The aim of this study was to evaluate the prevalence of biofilms in CRS patients and investigate the biofilm-related Toll-like receptor (TLR) and downstream NF-kappaB expression in sinus tissues of patients with CRS. Methods A total of 31 CRS patients and 11 control patients with other diseases undergoing endoscopic sinus surgery were recruited consecutively. Their random sinonasal tissue specimens were examined for the formation of biofilms by scanning electron microscopy. The relative levels of TLR2, TLR4, and NF-kappaB expression in those sinus tissues were determined by quantitative real-time reverse-transcriptase polymerase chain reaction and immunohistochemistry. Results Bacterial biofilms were detected in 20 of 31 samples from CRS patients but not in a single sample from control patients. The relative levels of TLR2, TLR4, and NF-kappaB expression in sinus tissues from CRS patients were significantly higher than that of controls, and the relative levels of TLR2 and NF-kappaB, but not TLR4, in biofilm-positive sinus tissues were significantly higher than that in biofilm-negative tissues of those CRS patients. Conclusion Our data indicated that bacterial biofilms were associated with higher levels of TLR2 and NF-kappaB in the majority of sinus tissues from patients with CRS.

T cell subsets in cord blood are influenced by maternal allergy and associated with atopic dermatitis.

This study aimed to investigate the influence of maternal allergy on cord blood regulatory and effector T cells and to evaluate their role as a predictor of atopic dermatitis (AD) during the first 2 yr of life.

Differential expression of Toll-like receptor pathway genes in chronic rhinosinusitis with or without nasal polyps

Abstract Conclusions: Our results indicate that chronic rhinosinusitis without nasal polyps (CRSsNP) is characterized by the down-regulation of a Toll-like receptor (TLR)-mediated signaling pathway and such a deficiency within the innate immune system may contribute to the inflammatory process of CRSsNP. In contrast, the inflammatory process found in CRS with nasal polyps (CRSwNP) is characterized by an excessively activated TLR-mediated signaling pathway, which may contribute to the formation of nasal polyps. This study suggests that the pathophysiologic mechanism of CRSsNP and CRSwNP is different. Objective: The nasal mucosa expresses a variety of TLRs that serve in recognizing microorganisms. We investigated the gene expression of a TLR-mediated signaling pathway within two distinctive patient subgroups: CRSwNP and CRSsNP. Methods: Nasal mucosal tissue was obtained from 78 subjects with CRS and 23 control subjects. qRT-PCR and immunohistochemistry were used to investigate tissues for the expression of TLR2, TLR4, TLR7, their downstream signaling components, MyD88 and TRIF, and associated cytokines, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-4, and IL-10. Results: TLR2, TLR4, TLR7, and IL-4 were significantly increased in CRSwNP patients when compared with either CRSsNP patients or control subjects, whereas TLR4 and TLR7, and downstream MyD88 were significantly decreased in CRSsNP patients versus patients from CRSwNP and control subjects.

Endoscopic management of the inverted papilloma with attachment to the frontal sinus drainage pathway

Conclusion. Extensive inverted papilloma (Krouse T3 lesions) with attachment to the frontal sinus drainage pathway can be treated successfully using an endoscopic approach. Objectives. The endoscopic management of inverted papilloma (IP) has gained in popularity over the last 15 years. However, the appropriate management of lesions involving the frontal sinus and its drainage pathway still has to be determined. Patients and methods. We performed a retrospective review of the results for patients with IP in the Otolaryngology, Head and Neck Surgery Department, Beijing Tongren Hospital from 2004 to 2007 to identify those patients with lesions involving the frontal sinus and its drainage pathway. By their appearance on nasal endoscopic examination and by computed tomography scanning, the tumors were defined using the Krouse staging system. Sinus endoscopy was used to screen for disease after endoscopic resection and the clinical outcomes were analyzed. Results. A total of nine patients (eight males and one female) were identified in which IP involved the frontal sinus and its drainage pathway. Preoperative and postoperative pathological examinations revealed IP as the diagnosis. All tumors were defined as T3 lesions. Four cases with lateral wall of frontal recess tumor attachment underwent an endoscopic Draf IIA frontal sinusotomy. Three cases with either lateral and posterior walls of frontal recess and frontal infundibulum attachment, or medial and posterior walls of frontal recess and frontal infundibulum attachment underwent a Draf IIB procedure. Two cases with posterior wall of frontal recess and frontal infundibulum attachment, or medial, lateral, and posterior walls of frontal recess and frontal infundibulum attachment underwent a Draf III procedure. All patients remain disease-free after an average follow-up period of 15 months.