Effect of di-(2-ethylhexyl) phthalate (DEHP) on allergic rhinitis.

Allergic rhinitis (AR) is a common chronic inflammatory disease of the upper respiratory tract. Di(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer and belongs to environmental endocrine disruptors (EDCs). It can be entered the human body which is harmful to health. The relationship between DEHP and AR is still inconclusive. This study aims to investigate the effect of environmental pollutants DEHP on AR. By examining DEHP metabolites in the urine of AR patients and building an AR model. 24 BALB/c mice were used as the study subjects, and ovalbumin (OVA) and DEHP (3 mg/kg/body) were used for intragastric administration. They were divided into control group, DEHP group, OVA group and OVA + DEHP group. Examination, behavioral scoring, inflammatory factor testing, oxidative stress testing, detection of aryl hydrocarbon receptor (AhR) and signaling pathways CYP1A1 and CYP1B1 related proteins and mRNA. The concentrations of 3 metabolites of DEHP (MEHHP, MEOHP, and MEHP) in urine of AR patients were higher. And HE-staining showed that for the control group, many chronic inflammatory cell infiltration and nasal mucosal destruction were observed in the OVA + DEHP group and were more severe than the OVA group. Allergic symptom scores were obtained from sneezing, scratching, number of scratching, and nose flow. The scores of the OVA group and the OVA + DEHP group were higher than 7 points. Serum ELISA and nasal mucosal oxidative stress tests are more serious in the OVA + DEHP group. The expression of AhR protein and its mRNA was increased in the DEHP group, OVA group and OVA + DEHP group. The OVA + DEHP group was more significant in the OVA group and DEHP group. And the mRNAs of the AhR-related signaling pathways CYP1A1 and CYP1B1 were also more prominent in the OVA + DEHP group. DEHP may aggravate its inflammatory response through the AhR pathway closely related to the environment. When combined with OVA, DEHP can further aggravate the OVA-induced nasal inflammatory response and make the nasal cavity have undergone severe changes, and many inflammatory cells have infiltrated. DEHP has shown an adjuvant effect, and the AhR-related signaling pathways CYP1A1 and CYP1B1 may be critical.

Genetic risk of FCRL3 and FCRL5 polymorphisms in children with asthma and allergic rhinitis in a Chinese Han population.

OBJECTIVES: Asthma and allergic rhinitis (AR) frequently occur as comorbid diseases of the upper airways. Single-nucleotide polymorphisms (SNPs) in the FCRL3 and FCRL5 genes have recently been shown to be associated with various immune-related disorders. This study evaluated the association of FCRL3 and FCRL5 polymorphisms with asthma and allergic rhinitis (AR) in a Han Chinese population. METHODS: Seven single nucleotide polymorphisms (SNPs) of the FCRL3 and FCRL5 were genotyped in 300 asthmatic children, and 206 healthy unrelated individuals using PCR-restriction fragment length polymorphism (PCR-RFLP) assay. Genotyping was validated by direct sequencing. RESULTS: Our results showed that the frequencies of the rs6692977 CT genotype and T allele within FCRL5 were significantly higher in asthma with comorbid AR compared to healthy controls (Bonferroni-corrected p (Pc) = 3.75 × 10-6; Pc = 0.006, respectively), whereas these of the CC genotype and C allele were significantly lower (Pc = 4.15 × 10-5; Pc = 0.006, respectively). The frequencies of the rs7528684 A allele (Pc = 1.80 × 10-3) and the rs10489678 G allele (Pc = 0.04) within FCRL3 were higher in asthma with comorbid AR than in controls. However, no differences in the tested genetic polymorphisms were detected between asthma and healthy individuals. CONCLUSION: This study identified novel SNPs in FCRL3 and FCRL5 significantly associated with the risk for asthma with comorbid AR in the Chinese population. The genetic variants may play role in the development of the asthma phenotype in children with asthma.

Prevalence of allergic rhinitis comorbidity with asthma and asthma with allergic rhinitis in China: A meta-analysis.

BACKGROUND: Allergic rhinitis (AR) and asthma are the most common inflammatory diseases of the airways. The relationship between asthma and AR is widely and clinically recognised. The concept "one airway, one disease" has been gradually accepted. However, in China, we could not find any systematic review and meta-analysis on the prevalence of AR with asthma and asthma with AR. OBJECTIVE: The aim of this research was to carry out a meta-analysis on the results of all conducted studies to present valid information about the co-occurrence rate of AR with asthma and asthma with AR in China. METHODS: Pubmed/Medline, Science, Springer, Elsevier, Embase, Wanfang data, VIP, CBM, and CNKI were searched systemically and data were extracted from eligible studies by two independent reviewers. Meta-analysis, study quality assessment, and publication bias assessments were all done using Stata 12.1 software. RESULTS: The results of this meta-analysis showed that pooled prevalence estimates of AR with asthma ranged from 6.69% to 14.35%, asthma with AR from 26.67% to 54%. Furthermore, an overall prevalence of 10.17% (95% CI 9.08-11.27%) was ascertained for AR with asthma, and 38.97% (95% CI 34.42-43.53%) for asthma with AR. CONCLUSIONS: The present meta-analysis comprehensively provided the first quantitative summary of the prevalence of AR with asthma and asthma with AR in China. Our study demonstrated that, in China, asthma and AR are often comorbid diseases and co-exist in the same patients. There is a close correlation between AR and asthma from an epidemiological standpoint.

Exposure to air pollution and risk of prevalence of childhood allergic rhinitis: A meta-analysis.

OBJECTIVES: Allergic rhinitis (AR), a common chronic inflammatory disease in the upper airways. The prevalence of AR in children seems to be increasing recently, and the most significant causes of the increase are thought to be changes in environmental factors, especially air pollution. However, we could not find any meta-analysis on the risk of air pollution exposure on the prevalence of AR in childhood. The aim of this research was to carry out a meta-analysis on the results of recent studies (21 s t century) to present valid information about exposure to air pollution and risk of prevalence of childhood AR. METHODS: PubMed, Science, Google Scholar, Elsevier and MDPI web database were searched up to January 1, 2000 to February 28, 2018. Including of air pollution and AR in childhood related to the observation of literature. Meta-analysis, study quality assessment, heterogeneity analysis and publication bias test were using Stata-MP 14.1 and Review Manager version 5.3 software. RESULTS: 13 studies will be included in the meta-analysis (8 cross-sectional studies, 5 cohort studies). Exposure to NO2 (OREurope = 1.031, 95%CI [1.002,1.060], P = 0.033; ORAsia = 1.236, 95%CI [1.099,1.390], P = 0.000; ORoverall = 1.138, 95%CI [1.052,1.231], P = 0.001); Exposure to SO2 (OREurope = 1.148, 95%CI [1.030,1.279], P = 0.012; ORAsia = 1.044, 95%CI [0.954,1.142], P = 0.352; ORoverall = 1.085, 95%CI [1.013,1.163], P = 0.020); Exposure to PM10 (OREurope = 1.190, 95%CI [1.092,1.297], P = 0.000; ORAsia = 1.075, 95%CI [0.995,1.161], P = 0.066; ORoverall = 1.125, 95%CI [1.062,1.191], P = 0.000); Exposure to PM2.5 (OREurope = 1.195, 95%CI [1.050,1.360], P = 0.007; ORAsia = 1.163, 95%CI [1.074,1.260], P = 0.000; ORoverall = 1.172, 95%CI [1.095,1.254], P = 0.000). CONCLUSIONS: Exposed to air pollution probable is a risk of prevalence of childhood AR. And the prevalence of AR will be increase when exposed to NO2, SO2, PM10 and PM2.5, but maybe the relationship between SO2/PM10 and prevalence of AR are not closely in Asia.

The airway inflammation induced by nasal inoculation of PM2.5 and the treatment of bacterial lysates in rats.

Particulate matter (PM) is one of the most important environmental issues in China. This study aimed to explore the correlation between PM2.5 and airway inflammation in healthy rats. The PM2.5 group was given an intranasal instillation of PM2.5 suspension on 15 consecutive days, and each received oral saline from day 16 to 90. The BV intervention group was treated as the PM2.5 exposure group, except that BV instead of saline was given daily. A histopathologic examination was performed to evaluate the airway inflammation. The prevalence and function of Th1/Th2/Treg/Th17 cells were detected by flow cytometry and ELISA. The expression of AhR was detected by western blot and real-time PCR. We found that epithelial damage and increased infiltration of inflammatory cell were present in the airways after PM2.5 exposure; there was an immune imbalance of Th cells in the PM2.5 group; the expression of AhR was increased in the airways after PM2.5 exposure. In the PM2.5 + BV group, we demonstrated alleviated immune imbalance and reduced inflammatory cell infiltration in the airways. Our study showed that exposure to PM2.5 induced airway inflammation. The imbalance of Th1/Th2/Treg/Th17 in PM2.5-induced airway inflammation might be associated with activation of the AhR pathway. Oral BV reduces PM2.5-induced airway inflammation and regulates systemic immune responses in rats.

Increased expression of IL-1R8 and a possible immunomodulatory role of its ligand IL-37 in allergic rhinitis patients.

Allergic rhinitis (AR) is a chronic inflammatory airway disease that is caused by an abnormal T cell response. T helper (Th)-17 cells and Th2 cells are the CD4+ T cell subsets implicated in the pathogenesis of AR. The suppression of excessive responses of these Th17 and Th2 cells has been reported to be an effective therapeutic approach to treat AR patients, and continuous efforts are being undertaken to find new methods to modulate the function of these cells. Recent studies have shown that IL-1R8 and its ligand IL-37 negatively regulate the immune response. In this study, we investigated the immunomodulatory the roles of IL-37/IL-1R8 axis in AR patients. We found that IL-1R8 expression was very low on dendritic cells (DCs) and resting CD4+ T cells but increased strongly on CD4+ T cells following T cell activation. Furthermore, IL-1R8 expression on CD4+ T cells was markedly higher in AR patients than in healthy controls. The IL-1R8 ligand IL-37 could act on CD4+ T cells to inhibit IL-17 and IL-4 production but could not influence DC-induced IL-17- and IL-4-producing CD4+ T cell responses. Meanwhile, recombinant IL-37 (rIL-37) did not influence IL-6, IL-1ß, and IL-10 production by DCs and expression of co-stimulatory molecules (including CD80, CD40, CD86 and HLA-DR) in DCs. Thus, IL-37 may regulate aberrant T cell immune response of allergic rhinitis mainly through CD4+ T cells, not DCs. The immunomodulatory roles of the IL-37/IL-1R8 axis indicate the therapeutic potential of this axis in AR.

Decreased expression of interleukin­37 and its anti­inflammatory effect in allergic rhinitis.

Interleukin­37 (IL­37), a novel member of the IL­1 cytokine family has been identified as a natural suppressor of innate immunity and inflammatory responses. The present study aimed to determine the expression of IL­37 in peripheral blood mononuclear cells (PBMCs) from patients with allergic rhinitis (AR), and examine the possible immunosuppressive effect of IL­37 on inflammatory mediators and CD4+ T cells in the pathogenesis of AR. The expression levels of IL­37 were determined in PBMCs from 39 patients with AR and 43 controls using reverse transcription­quantitative polymerase chain reaction (RT­qPCR) analysis and flow cytometry. Cytokines in the supernatants of the PBMCs and CD4+ T cells, which were stimulated with lipopolysaccharide in the presence or absence of IL­37, were assayed using enzyme­linked immunosorbent assays and RT­qPCR analysis. The results showed that the patients with AR exhibited significantly decreased expression of IL­37, and increased expression levels of interleukin (IL)­1ß and IL­6 in PBMCs. Recombinant IL­37 (rIL­37) inhibited the production of IL­1p and IL­6, and enhanced the production of IL­27 in PBMCs from the patients with AR and the control individuals. rIL­37 also markedly decreased the expression of IL­17 by CD4+ T cells in the patients with AR and controls. These results suggested that IL­37 may be an important cytokine in the pathogenesis of AR. It may have a protective role in AR by inhibiting the production of proinflammatory cytokines and through suppressive regulation of the Th17 response.

Association between TNFSF4 and BLK gene polymorphisms and susceptibility to allergic rhinitis.

Allergic rhinitis (AR) is a common inflammatory disease of the upper airway. Recent evidence suggests that gene­gene interactions between tumor necrosis factor receptor superfamily 4 (TNFSF4) and B cell lymphocyte kinase (BLK) may have a synergistic effect on T and B cells in determining immunologic aberration, via the nuclear factor­κB pathway. The present study was performed to evaluate the potential association between specific single nucleotide polymorphisms (SNPs) in the TNFSF4 and BKL genes with susceptibility to AR in Chinese subjects. A population­based case­control study was performed in 600 Chinese AR patients and 700 controls. Blood was drawn for DNA extraction, and 9 SNPs (6 in TNFSF4 and 3 in BKL genes) were selected and genotyped. The TNFSF4 SNPs rs1234314 and rs1234315, and the BLK SNPs rs13277113 and rs1600249 were observed to occur in different frequencies between the AR patients and the controls. The CC (rs1234314, rs1234315) and AA (rs1600249, rs13277113) genotypes provided protective effects against AR, whereas the AG (rs13277113) genotype presented a risk factor for AR. The haplotypes ACC in the rs1234313­rs1234314­rs1234315 block and GA in the rs2254546­rs13277113 block significantly decreased the risk of AR, whereas the GGT and AG haplotypes served protective roles. SNP interaction analysis further indicated that there may be synergistic effects among the selected sets of polymorphisms. The present study suggests a novel association between specific TNFSF4 and BLK gene polymorphisms and AR risk, highlighting their potential utility as genetic biomarkers for AR susceptibility in a Chinese Han population.

Association between PTPN22/CTLA-4 Gene Polymorphism and Allergic Rhinitis with Asthma in Children.

Allergic rhinitis (AR) is an IgE-mediated upper airway disease, and its impact on asthma has been widely recognized. Protein tyrosine phosphatase non-receptor 22 (PTPN22) gene and the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) gene polymorphisms have been reported to be associated with several immune-related diseases. Here we investigated the reffect of these two genes' polymorphisms on the risk of AR and asthma in Chinese Han children. A total of 106 AR patients, 112 AR with asthma patients, and 109 healthy children were enrolled in the study. The SNPs of PTPN22 (rs2488457, rs1310182, rs3789604) and CTLA-4 (rs3087243, rs11571302, rs11571315, rs231725, rs335219727, and rs4553808) were genotyped using a PCR-restriction fragment length polymorphism assay. For PTPN22, an increased prevalence of the CC genotype and C allele in rs1310182 were identified in AR group. For CTLA-4, AA genotype and A allele in rs3087243 and rs231725 were increased in AR with asthma group while in AR group, AA genotype and A allele in rs231725 were obviously decreased. This study reveals a significant association between SNPs in PTPN22, CTLA-4 gene and AR with asthma in Chinese Han children, which might be susceptibility factors for AR and asthma.

Evaluation on health-related quality of life in deaf children with cochlear implant in China.

OBJECTIVE: Previous studies have shown that deaf children benefit considerably from cochlear implants. These improvements are found in areas such as speech perception, speech production, and audiology-verbal performance. Despite the increasing prevalence of cochlear implants in China, few studies have reported on health-related quality of life in children with cochlear implants. The main objective of this study was to explore health-related quality of life on children with cochlear implants in South-west China. STUDY DESIGN: A retrospective observational study of 213 CI users in Southwest China between 2010 and 2013. METHODS: Participants were 213 individuals with bilateral severe-to-profound hearing loss who wore unilateral cochlear implants. The Nijmegen Cochlear Implant Questionnaire and Health Utility Index Mark III were used pre-implantation and 1 year post-implantation. Additionally, 1-year postoperative scores for Mandarin speech perception were compared with preoperative scores. RESULTS: Health-related quality of life improved post-operation with scores on the Nijmegen Cochlear Implant Questionnaire improving significantly in all subdomains, and the Health Utility Index 3 showing a significant improvement in the utility score and the subdomains of ''hearing," ''speech," and "emotion". Additionally, a significant improvement in speech recognition scores was found. No significant correlation was found between increased in quality of life and speech perception scores. CONCLUSION: Health-related quality of life and speech recognition in prelingual deaf children significantly improved post-operation. The lack of correlation between quality of life and speech perception suggests that when evaluating performance post-implantation in prelingual deaf children and adolescents, measures of both speech perception and quality of life should be used.

Genetic risk of TNFSF4 and FAM167A-BLK polymorphisms in children with asthma and allergic rhinitis in a Han Chinese population.

BACKGROUND: Asthma and allergic rhinitis (AR) frequently occur as comorbid diseases of the upper airways. Single-nucleotide polymorphisms (SNPs) in the TNFSF4 and FAM167A-BLK genes have recently been shown to be associated with various immune-related disorders. OBJECTIVE: Our aim was to determine whether TNFSF4 or FAM167A-BLK polymorphisms confer genetic susceptibility to asthma and AR in a Han Chinese population. METHODS: We performed a case-control study of 290 asthmatic children and 252 healthy controls. Nine SNPs in the TNFSF4 region (rs1234313, rs1234314, rs1234315, rsl 2039904, rs844648 and rsl 0912580) and the FAM167A-BLK region (rs2254546, rs13277113 and rs1600249) were detected using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS: This study revealed that three SNPs in TNFSF4 (rsl 234313, rsl 234314 and rsl 234315) and two SNPs in FAM167A-BLK (rs2254546 and rsl 600249) were significantly correlated with asthma and AR, while SNP rsl600249 was associated with asthma without allergic rhinitis as a risk factor. Further, we demonstrated synergistic effects between the TNFSF4 and FAM167A-BLK SNPs. CONCLUSION: This study supports that the SNPs in TNFSF4 and FAM167A-BLK may be involved in asthma and AR gene risk in the Han Chinese cohort.

Association between JAK1 gene polymorphisms and susceptibility to allergic rhinitis.

OBJECTIVES: Allergic rhinitis (AR) is an inflammatory disorder of the upper airway. Janus kinase 1 (JAK1), a member of JAK family, has recently been found to participate in the immune response and the development of allergic airway disease. This study was performed to evaluate the potential association of JAK1 polymorphisms with AR in a Chinese Han population. METHODS: A case-control study was performed in 450 Chinese AR patients and 615 healthy controls. Three SNPs in the JAK1 gene, rs3790532, rs310241 and rs2780815, were analyzed using a polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP). RESULTS: An association was detected between SNP rs310241 in the JAK1 gene and AR in a Chinese Han population. However, no significant association was observed between the polymorphisms rs3790532 and rs2780815 and AR. For rs310241, the CC genotype and the C allele significantly increased the risk of AR. Furthermore, we found that the ACG haplotype in JAK1 gene was positively correlated with AR, while the GTG haplotype was associated with a significantly decreased risk of AR. CONCLUSION: This study indicates that the JAK1 rs310241 C-related genotype and allele are involved in AR susceptibility, making them potentially useful genetic biomarkers for AR susceptibility in the Chinese Han population.

Changes in circulating follicular helper T-cells in Chinese patients with allergic rhinitis.

CONCLUSIONS: Changes of circulating Follicular helper T (cTfh) cells existed in allergic rhinitis (AR) patients, and the severity of disease was associated with a more severe change of cTfh milieu. These results imply that cTfh cells may play a crucial role in the pathology of AR in Chinese patients. OBJECTIVES: The aim of this study was to investigate the changes in cTfh cells in Chinese AR patients. METHODS: Fifty-two patients were studied (32 in the AR group and 20 in the control group) for this research. The cTfh cell frequency and mRNA levels of transcription factor Bcl-6, B lymphocyte induced maturation protein 1 (BLIMP-1), and related cytokine IL-21 (IL-21 protein was also measured) were analyzed. Clinical severity was evaluated by total serum IgE levels, visual analog scale scores (VAS), and rhino-conjunctivitis quality-of-life questionnaires (RQLQ). RESULTS: The frequency of cTfh cells were elevated in AR groups vs healthy controls (p < 0.05). Levels of IL-21 mRNA, Bcl-6 mRNA and the level of IL-21 protein were also significantly higher in the AR groups (p < 0.05), whereas BLIMP-1 mRNA was decreased (p < 0.05). Furthermore, positive correlations were identified between the frequency of cTfh cells and indicators of clinical severity (p < 0.01).

High frequency of T helper type 9 cells in Chinese patients with allergic rhinitis.

BACKGROUND: T helper type 9 cells (Th9) are the most recently discovered subset of Th cells, and are involved in the pathology of several autoimmune and allergic diseases. The significance of Th9 cells in allergic rhinitis (AR) in Chinese patients is unclear. OBJECTIVE: The aim of this study was to investigate the possible role of Th9 cells in AR in Chinese patients. METHODS: Th9 cells and related factors were assessed by measuring levels of interleukin-9 (IL-9), PU.1, interferon-regulatory factor 4 (IRF4), and numbers of Th9 cells. A Th9-polarized milieu was evaluated by determining the levels of IL-4 and transforming growth factor-ß1 (TGF-ß1). Disease severity was assessed by rhino-conjunctivitis quality of life questionnaires (RQLQ), visual analog scale scores (VAS), and peripheral eosinophils (EOS) count. RESULTS: Levels of IL-4 and TGF-ß1 were elevated in AR groups versus healthy controls (P < 0.05). Levels of IL-9, PU.1, IRF4, and the numbers of Th9 cells were also significantly higher in the AR groups (P < 0.05). Furthermore, positive correlations were identified between IL-9 levels and EOS expression, RQLQ, and VAS scores (P < 0.01). CONCLUSIONS: Th9 cells and their relative factors were elevated in AR patients. Levels of Th9 polarization-related factors were much higher in AR patients, and the severity of disease was associated with a more severe Th9 response. These results suggest that AR patients present a favorable environment for Th9 differentiation, and that Th9 cells may play a crucial role in the pathology of AR in Chinese patients.

MicroRNA expression profile of mature dendritic cell in chronic rhinosinusitis.

OBJECTIVE: Chronic rhinosinusitis (CRS), which includes CRS without nasal polyposis (CRSsNP) and with nasal polyposis (CRSwNP), shows imbalance of helper T cells (Th) and regulatory T cells (Treg). The balance of Th and Treg cells is orchestrated by dendritic cells (DCs). Recent studies show functions of DCs can be regulated by microRNAs (miRNAs or miRs). This study is aimed to investigate miRNAs expression profiles of peripheral blood DCs in CRS. METHODS: Peripheral blood samples of 30 patients with CRS and 7 patients with nasal septum deviation alone were collected. CD14(+) monocytes were isolated from these samples and differentiated into dendritic cells (DCs). Small RNAs were extracted from mature DCs and reversely transcribed into cDNA by Mir-XTM miRNA First-Strand synthesis method. MiRNA microarrays were used for miRNA expression analysis. Microarray results were validated by real-time PCR performed on five top list target genes. RESULTS: MiRNA microarrays showed that DCs from different types of patients have different sets of differential expressed miRNAs when comparing with Controls; they also share 31 commonly changed miRNAs among all three groups of CRS patients. Of these 31 miRNAs, 5 miRNAs were up-regulated and 25 miRNAs were down-regulated in all three types of CRS, while MiR-1290 was down-regulated in CRSsNP but up-regulated in both atopic CRSwNP and non-atopic CRSwNP. CONCLUSIONS: By comparing miRNA gene expression patterns in 3 types of CRS patients, we have been able to identify candidate miRNAs that might mediate the core pathogenesis of CRS through regulating dendritic cells. These miRNAs could serve as potential therapeutic targets for CRS.

FCRL3 gene polymorphisms confer risk for sudden sensorineural hearing loss in a Chinese Han Population.

Fc receptor-like 3 (FCRL3) has recently been associated with susceptibility to several immune-related diseases. In this study, we evaluated the potential association of FCRL3 polymorphisms with sudden sensorineural hearing loss (SSNHL) in a Chinese Han population. Five single-nucleotide polymorphisms (SNPs) in FCRL3-rs945635, rs3761959, rs7522061, rs10489678, and rs7528684-were genotyped in 630 patients with SSNHL and 600 healthy controls by using a PCR-restriction fragment length polymorphism assay. The allele, genotype, and haplotype frequencies in the patients and the controls were compared using a χ(2) test. Moreover, we performed haplotype analysis by using the online software platform SHEsis. The results revealed a significant association between three SNPs-rs7528684, rs3761959, and rs7522061-and SSNHL in the studied Chinese Han population. Furthermore, the AGT and GAC haplotypes were associated with a significantly higher prevalence of SSNHL than were the GAT, GGC and GGT haplotypes. However, no significant differences were detected in either the genotype or allele frequencies of the other two SNPs, rs945635 and rs10489678, between the SSNHL and control groups. Overall, this study has identified an association between FCRL3 polymorphisms and increased risk of SSNHL in a Chinese Han population.

FCRL3 gene polymorphisms confer autoimmunity risk for allergic rhinitis in a Chinese Han population.

BACKGROUND: Heredity and environmental exposures may contribute to a predisposition to allergic rhinitis (AR). Autoimmunity may also involve into this pathologic process. FCRL3 (Fc receptor-like 3 gene), a novel immunoregulatory gene, has recently been reported to play a role in autoimmune diseases. OBJECTIVE: This study was performed to evaluate the potential association of FCRL3 polymorphisms with AR in a Chinese Han population. METHODS: Five single-nucleotide polymorphisms of FCRL3, rs945635, rs3761959, rs7522061, rs10489678 and rs7528684 were genotyped in 540 AR patients and 600 healthy controls using a PCR-restriction fragment length polymorphism assay. Allele, genotype and haplotype frequencies were compared between patients and controls using the χ2 test. The online software platform SHEsis was used to analyze their haplotypes. RESULTS: This study identified three strong risk SNPs rs7528684, rs10489678, rs7522061 and one weak risk SNP rs945635 of FCRL3 in Chinese Han AR patients. For rs7528684, a significantly increased prevalence of the AA genotype and A allele in AR patients was recorded. The frequency of the GG genotype and G allele of rs10489678 was markedly higher in AR patients than those in controls. For rs7522061, a higher frequency of the TT genotype, and a lower frequency of the CT genotype were found in AR patients. Concerning rs945635, a lower frequency of the CC genotype, and a higher frequency of G allele were observed in AR patients. According to the analysis of the three strong positive SNPs, the haplotype of AGT increased significantly in AR cases (AR = 38.8%, Controls = 24.3%, P = 8.29 × 10(-14), OR [95% CI] 1.978 [1.652~2.368]). CONCLUSIONS: This study found a significant association between the SNPs in FCRL3 gene and AR in Chinese Han patients. The results suggest these gene polymorphisms might be the autoimmunity risk for AR.

Association study between interleukin-12 receptor ß1/ß2 genes and allergic rhinitis in the Chinese Han population.

Interleukin-12 (IL-12) plays a key role in the protection against allergic reaction induced by allergen as well as the differentiation of T helper 1 cells in patients with allergic rhinitis (AR), exerting its biological effects through binding to specific IL-12 receptors (IL-12Rs) termed IL-12Rß1 and IL-12Rß2. In this study, we investigated the relationship between polymorphisms in the IL-12R gene and AR in the Chinese Han population. A total of 543 patients with AR and 749 normal controls were genotyped for IL-12Rß1/rs438421, IL-12Rß2/rs3790565, rs3790567, and rs6679356 using a PCR restriction fragment length polymorphism analysis. The association study of each polymorphism of the IL-12Rß1 and IL-12Rß2 gene and AR showed that a significantly increased prevalence of the homozygous rs438421 GG genotype and G allele appeared in the AR patients compared with healthy controls. A significantly decreased prevalence of AG in rs438421 in AR patients is compared with healthy controls. Our research demonstrated an important association between polymorphisms in IL-12Rß1 and AR in the Chinese Han population. A strong association between rs438421 in a single nucleotide polymorphism of IL-12Rß1 and AR was identified.

Allergen induced Treg response in the peripheral blood mononuclear cells (PBMCs) of patients with nasal polyposis.

BACKGROUND: Nasal polyposis (NP) is a chronic inflammatory disease of the nasal cavity and sinuses regulated by T cells. Regulatory T (Treg) cells are involved in controlling immune responses and inhibiting the allergen-specific effector cell response. The aim of this study was to evaluate whether NP patients had defects in Treg cells after specific allergen exposure and the possible correlation between atopy and Treg cells. METHODS: Peripheral blood mononuclear cells (PBMCs), isolated from NP patients and controls, were cultured with allergen+phytohemagglutinin (PHA) or PHA stimulation for 48h. The frequency of CD4+CD25+Foxp3+ cells was measured by flow cytometry. The level of Foxp3 was measured by Real-time PCR. Concentrations of Interferon-γ (IFN-γ), Interleukin-4 (IL-4), Interleukin-5 (IL-5), Interleukin-10 (IL-10) and transforming growth factor-ß (TGF-ß) in culture supernatants were determined by ELISA. RESULTS: Both atopic and non-atopic NP patients had a significantly decreased frequency of Treg cells and Foxp3 level in allergen stimulated PBMCs, also significantly decreased TGF-ß level in culture supernatants. The decrease was even more striking in the atopic group. Also, there were significantly negative correlations between Treg cells and IFN-γ, IL-4, IL-5. Moreover, inthe atopic group, allergen stimulation downregulated Treg cells and increased IFN-γ, IL-4, IL-5 levels, while upregulating Treg cells and decreasing IFN-γ, IL-4, IL-5 levels in controls. CONCLUSIONS: Patients with NP have a defective Treg cell response after allergen stimulation which is related to excessive Th1 and Th2 responses to specific allergens. Atopy may increase the impairment of Treg and exacerbate NP through the defective suppression of Treg on Th1 and Th2.