A Cohort Study on Deficiency of ADA2 from China.

PURPOSE: Deficiency of adenosine deaminase 2 (DADA2), an autosomal recessive autoinflammatory disorder caused by biallelic loss-of-function variants in adenosine deaminase 2 (ADA2), has not been systemically investigated in Chinese population yet. We aim to further characterize DADA2 cases in China. METHODS: A retrospective analysis of patients with DADA2 identified through whole exome sequencing (WES) at seventeen rheumatology centers across China was conducted. Clinical characteristics, laboratory findings, genotype, and treatment response were analyzed. RESULTS: Thirty patients with DADA2 were enrolled between January 2015 and December 2021. Adenosine deaminase 2 enzymatic activity was low in all tested cases to confirm pathogenicity. Median age of disease presentation was 4.3 years and the median age at diagnosis was 7.8 years. All but one patient presented during childhood and two subjects died from complications of their disease. The patients most commonly presented with systemic inflammation (92.9%), vasculitis (86.7%), and hypogammaglobinemia (73.3%) while one patient presented with bone marrow failure (BMF) with variable cytopenia. Twenty-three (76.7%) patients were treated with TNF inhibitors (TNFi), while two (6.7%) underwent hematopoietic stem cell transplantation (HSCT). They all achieved clinical remission. A total of thirty-nine ADA2 causative variants were identified, six of which were novel. CONCLUSION: To establish early diagnosis and improve clinical outcomes, genetic screening and/or testing of ADA2 enzymatic activity should be performed in patients with suspected clinical features. TNFi is considered as first line treatment for those with vascular phenotypes. HSCT may be beneficial for those with hematological disease or in those who are refractory to TNFi.

Chinese Expert Consensus on the Use of Biologics in Patients with Chronic Rhinosinusitis (2022, Zhuhai).

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

Texture analysis of conventional magnetic resonance imaging and diffusion-weighted imaging for distinguishing sinonasal non-Hodgkin's lymphoma from squamous cell carcinoma.

PURPOSE: To evaluate the value of texture analysis (TA) of conventional magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) in the differential diagnosis between sinonasal non-Hodgkin's lymphoma (NHL) and squamous cell carcinoma (SCC). METHODS: Forty-two patients with sinonasal SCC and 30 patients with NHL were retrospectively enrolled. TAs were performed on T2-weighted image (T2WI), apparent diffusion coefficient (ADC) and contrast-enhanced T1-weighted image (T1WI). Texture parameters, including mean value, skewness, kurtosis, entropy and uniformity were obtained and compared between sinonasal SCC and NHL groups. Receiver-operating characteristic (ROC) curves and logistic regression analyses were used to evaluate the diagnostic value and identify the independent TA parameters. RESULTS: The mean value and entropy of ADC, and mean value of contrast-enhanced T1WI were significantly lower in the sinonasal NHL group than those in the SCC group (all P < 0.05). ROC analysis indicated that the entropy of ADC had the best diagnostic performance (AUC 0.832; Sensitivity 0.95; Specificity 0.67; Cutoff value 6.522). Logistic regression analysis showed that the entropy of ADC (P = 0.002, OR = 26.990) was the independent parameter for differentiating sinonasal NHL from SCC. CONCLUSION: TA parameters of conventional MRI and DWI, particularly the entropy value of ADC, might be useful in the differentiating diagnosis between sinonasal NHL and SCC.

Polymorphisms in MicroRNA Target Sites of TGF-ß Signaling Pathway Genes and Susceptibility to Allergic Rhinitis.

BACKGROUND: The polymorphisms inside microRNA target sites locating in the 3'-UTR region may introduce the micro-RNA-binding changes, which may regulate the gene expression and correlate with the potential diseases. OBJECTIVES: We aimed to investigate whether the polymorphisms in microRNA target sites of transforming growth factor beta (TGF-ß) signaling pathway genes are associated with the susceptibility of mite-sensitized allergic rhinitis (AR) in a Han Chinese population. METHODS: In this case-control study, 454 AR patients and 448 healthy controls were recruited. Three HapMap single-nucleotide polymorphisms (SNPs) were mapped to putative microRNA recognition sites and genotyped by TaqMan allelic discrimination assay. RESULTS: The genotype and allele frequencies of 3 SNPs (rs1590 in TGFBR1; rs1434536 and rs17023107 in BMPR1B) showed lack of significant association with AR. However, in the subgroup analysis, the TG, GG, and TG/GG genotypes of rs1590 exhibited significantly increased risk of AR in the male subgroup (TG: adjusted OR = 1.57, 95% CI = 1.08-2.31; GG: adjusted OR = 1.76, 95% CI = 1.09-2.86; TG/GG: adjusted OR = 1.62, 95% CI = 1.13-2.33). The CT genotypes of rs17023107 might have potential to protect against AR in the patients age of <15 years (adjusted OR = 0.37, 95% CI = 0.14-0.95) and the males (adjusted OR = 0.48, 95% CI = 0.25-0.95). No significant association was found between SNPs and the total serum IgE level. CONCLUSIONS: In a Han Chinese population, stratified by age and gender, susceptibility to mite-sensitized AR may be associated with 2 SNPs (rs1590 and rs17023107) in microRNA target sites of TGF-ß signaling pathway genes.

[Clinical and laboratory features of macrophage activation syndrome].

OBJECTIVE: To study the clinical and laboratory features of macrophage activation syndrome (MAS) at the early stage of diagnosis, and to explore a method for early identification of MAS. METHODS: A retrospective analysis was performed for the demographic data, clinical and laboratory features, and treatment outcomes of 21 MAS patients. RESULTS: Of the 21 MAS patients, 14 had systemic juvenile idiopathic arthritis, 5 had Kawasaki disease (KD), and 2 had connective tissue disease (CTD) as primary diseases. The median time of MAS onset was 19 days. The KD patients had the shortest time of MAS onset, while the CTD patients had the longest onset time (P=0.009). The top 10 clinical symptoms were fever (95%), rash (86%), lymph node enlargement (67%), hemophagocytic phenomenon in bone marrow (63%), pulmonary disease (62%), serous effusion (62%), hepatomegaly (52%), cerebrospinal fluid abnormalities (50%), central nervous system damage (43%), and splenomegaly (38%). The median of hemoglobin level was lower than the normal value. The medians of C-reactive protein level and erythrocyte sedimentation rate were higher than the normal values. There were significant increases in serum ferritin, glutamic-pyruvic transaminase, aspartate aminotransferase, lactate dehydrogenase, and triglyceride. The median of fibrinogen level was lower than the normal value. There were significant increases in D-dimer, interleukin-6 (IL-6), interleukin-10 (IL-10), and interferon-γ (IFN-γ). Of the 21 patients, 20 were improved and discharged. CONCLUSIONS: If patients with rheumatic disease have persistent fever, hepatic dysfunction, coagulation disorders, multiple organ impairment, significantly increased IL-10 and IFN-γ, and a persistent increase in serum ferritin, the development of MAS should be considered.

[Association of vitamin D concentrations with juvenile idiopathic arthritis].

OBJECTIVE: 25-Hydroxyvitamin D3 [25(OH)D3] is the main product of vitamin D and can reflect the absolute concentration of active vitamin D in the body. This study examined serum 25(OH)D3 levels in children with juvenile idiopathic arthritis (JIA) in order to explore the association of vitamin D concentrations with the pathogenesis and disease activity of JIA. METHODS: Serum samples were collected from 53 children confirmed as having JIA between January 2013 and March 2014, as well as 106 healthy children (control group) who underwent physical examination in the same period. Serum concentrations of 25(OH)D3 were measured using ELISA and compared between the cases and healthy controls. The association of serum 25(OH)D3 levels with JIA subtypes, ACR Pediatric 30 Score, peripheral blood C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were analyzed in children with JIA. RESULTS: Compared with the control group, the JIA group had significantly reduced serum 25(OH)D3 levels (median: 42.6 nmol/L vs 49.9 nmol/L; P<0.01). The percentage of subjects with severe deficiency of vitamin D in the JIA group was significantly higher than that in the control group (17.0% vs 6.6%; P<0.05). Serum 25(OH)D3 showed no significant correlations with JIA subtypes, ACR Pediatric 30 Score, CRP, and ESR in children with JIA. CONCLUSIONS: Vitamin D concentrations are significantly decreased in children with JIA. Decreased vitamin D concentrations may be associated with the pathogenesis of JIA. However, vitamin D concentrations may have no correlations with JIA subtypes, disease severity, and disease activity.

[Risk factors for pleural lung disease in children with juvenile idiopathic arthritis].

OBJECTIVE: To investigate the risk factors for pleural lung disease (PLD) in children with juvenile idiopathic arthritis (JIA) and to provide a basis for the early diagnosis and timely treatment of this disease. METHODS: A total of 360 children with a confirmed diagnosis of JIA were enrolled, and their clinical data were retrospectively analyzed. All patients underwent a chest X-ray. The patients with PLD were assigned to PLD group, while those without PLD were assigned to non-PLD group. The clinical, imaging, and laboratory results of JIA patients with PLD were analyzed. RESULTS: Among the 360 JIA patients, 43 (11.9%) had PLD, and 9 (21%) of them had respiratory symptoms. Chest X-ray findings mainly included interstitial pneumonitis (53.5%) and pleurisy and/or pleural effusion (38.1%). In the 43 cases of JIA-PLD, 4 (9.3%) had normal chest X-ray findings but abnormal chest CT findings. The incidence of PLD was relatively high in patients aged under 3 years and those aged 12 years or above. Children with systemic JIA had a relatively high incidence of PLD. Compared with the non-PLD group, the PLD group had a significantly higher incidence of anemia, elevated white blood cell (WBC) count and IgG levels in peripheral blood, and positive rheumatoid factors or antinuclear antibodies (P<0.05). CONCLUSIONS: Among children with JIA, PLD is mostly seen in patients with systemic JIA or aged <3 years or ≥ 12 years, especially those with anemia, elevated WBC count and IgG levels, and positive rheumatoid factors or antinuclear antibodies. For JIA patients with PLD, interstitial pneumonitis is usually seen on chest X-ray or CT, but respiratory symptoms are rarely observed. Routine use of high-resolution chest CT is recommended for early diagnosis and timely treatment of PLD in children with JIA.

[Serum cytokine levels in children with newly diagnosed active systemic juvenile idiopathic arthritis].

OBJECTIVE: To study the changes in serum cytokines levels in children with newly diagnosed active systemic juvenile idiopathic arthritis (SJIA) and to explore the role of cytokines in the development and progression of SJIA. METHODS: Seventy-four pediatric patients with active SJIA between January 2010 and December 2013 were included in the study. Serum levels of interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukine-10 (IL-10), tumor necrosis factor (TNF), and interferon gamma (IFN-γ) were measured by flow cytometry in these patients. The levels of cytokines were also determined in 202 healthy children as the control group. Routine laboratory parameters including white blood cell (WBC) count, percentage of neutrophils, hemoglobin level, platelet count, hypersensitive C-reactive protein (hs-CRP), and erythrocyte sedimentation rate (ESR) were monitored in the patient group. RESULTS: The WBC count, percentage of neutrophils, hs-CRP, and ESR in 74 cases of SJIA were significantly above the normal range, their platelet counts were within the normal range, whereas hemoglobin levels were below the normal range. Compared with the control group, the patient group showed a significantly increased level of IL-6 (P<0.01) and significantly reduced levels of IL-4, IL-10, and TNF (P<0.01). However, there were no significant changes in serum levels of IL-2 and IFN-γ in the patient group (P>0.05). In SJIA children, IL-6 level, which was significantly elevated, was negatively correlated with hemoglobin level, which was significantly reduced (r=-0.244, P<0.05). CONCLUSIONS: Serum level of IL-6 is significantly increased in children with SJIA, and it has a negative correlation with anemia.

Combination of omalizumab with allergen immunotherapy versus immunotherapy alone for allergic diseases: A meta-analysis of randomized controlled trials.

BACKGROUND: Allergen immunotherapy (AIT)-associated adverse events (AEs) limit its usage in the management of allergic diseases. The monoclonal anti-IgE antibody (omalizumab) and AIT have complementary actions. However, no consensus has been reached on whether their combination could exert superior efficacy and safety. OBJECTIVE: To evaluate whether the combination of AIT with omalizumab is superior to AIT alone in treating allergic diseases. METHODS: The MEDLINE/PubMed, Embase, Scopus and Cochrane Library databases were searched to identify randomized control trials (RCTs) reporting the outcomes of omalizumab combined with AIT (omalizumab + AIT) versus AIT alone. A random-effect model was established to estimate outcomes with a 95% confidence interval (CI). RESULTS: A total of 11 eligible RCTs (involving 901 patients) were screened out for the meta-analysis. According to a pooled analysis, omalizumab + AIT significantly increased the number of patients achieving the target maintenance dose (TMD) and sustained unresponsiveness (SU) to allergens (odds ratio [OR] = 2.43; 95% CI: 1.33-4.44; p = 0.004; I2 = 35%, and OR = 6.77; 95% CI: 2.10-21.80; p = 0.001; I2 = 36%, respectively). Similarly, individuals receiving the combination therapy reported significantly fewer episodes of severe systemic AEs than AIT alone (OR = 0.32; 95% CI: 0.18-0.59; p = 0.0003; I2 = 0%). Meanwhile, the improvements in symptom severity score (mean difference [MD] = -0.26), rescue medication daily means score (MD = -0.14), and number of patients consuming epinephrine in AIT (OR = 0.20) were all more evident than those in AIT alone. CONCLUSION: Omalizumab + AIT can significantly enhance the efficacy and safety of AIT by increasing TMD and SU to allergens, while decreasing severe systemic AEs.

Incidence and prognosis of olfactory and gustatory dysfunctions related to SARS-CoV-2 Omicron strain infection in China: A national multicenter survey of 35,566 individuals.

Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

Texture analysis of diffusion kurtosis imaging for differentiating malignant from benign sinonasal lesions: added value to conventional imaging features.

OBJECTIVES: To evaluate the performance of texture analysis (TA) of diffusion kurtosis imaging (DKI) in differentiating malignant from benign sinonasal lesions, and its added value to the conventional imaging features. METHODS: Fifty-eight patients with malignant and 40 patients with benign sinonasal lesions were retrospectively enrolled. Conventional CT and MRI features were reviewed. Texture parameters were obtained and compared between two groups. Multivariate logistic regression analysis was used to identify the most valuable variables. Receiver operating characteristic curves were performed to assess the differentiating performance of independent variables and their combination. RESULTS: There were significant differences in tumor necrosis, bone erosion and soft tissue invasion between the two groups (all p < 0.05). There were significant differences in the 10th and entropy of Apparent diffusion coefficient map, the mean, 10th and entropy of D map, the mean and 90th of K map between the two groups (all p < 0.002). The bone erosion, entropy of D, and mean of K were independent variables associated with malignant tumors. Receiver operating characteristic analyses indicated that the combination of three features possessed better differentiating performance than bone erosion alone (p = 0.003). CONCLUSION: TA of DKI could supply incremental value to conventional imaging features for pre-operative differential diagnosis between benign and malignant sinonasal lesions. ADVANCES IN KNOWLEDGE: The present study is the first to combine conventional imaging features and the TA of DKI in the differential diagnosis between benign and malignant sinonasal lesions. Our findings suggest that TA of DKI could supply incremental value to conventional imaging features.

Evaluation of genetic variants in ferroptosis-related genes and house dust mite-induced allergic rhinitis risk.

BACKGROUND: Ferroptosis-related genes disrupt iron homeostasis and enhance lipid peroxidation to initiate respiratory system diseases. However, the association between genetic variants in the ferroptosis-related genes with house dust mite (HDM)-induced allergic rhinitis (AR) susceptibility remains unclear. METHODS: A case-control study, involving 222 cases and 237 healthy controls from a Chinese population, was conducted to evaluate the relationship between single nucleotide polymorphisms (SNPs) in ferroptosis-related genes and HDM-induced AR risk. A gene-based analysis was performed by multi-marker analysis of genomic annotation (MAGMA) to identify candidate associated ferroptosis-related genes. A logistic regression model and joint analysis were used to assess the effect of SNPs on HDM-induced AR susceptibility. RESULTS: Two independent SNPs (rs2305128 in ENPP2 and rs1868088 in EPAS1) were significantly associated with HDM-induced AR risk (OR = 1.82, 95% CI = 1.19-2.79, P = 5.98 × 10-3, PFDR = 4.88 × 10-2; OR = 2.14, 95% CI = 1.23-3.72, P = 6.95 × 10-3, PFDR = 4.87 × 10-2, respectively). Moreover, combined analysis of these two SNPs revealed that an increased risk of HDM-induced AR was positively associated with an increasing number of risk genotypes (Ptrend = 8.48 × 10-5). The stratification analysis showed that the cumulative effect of two SNPs on HDM-induced AR risk was more pronounced among patients presenting more serious symptoms and harboring one or two risk genotypes. CONCLUSIONS: These findings suggest that the genetic variants in ferroptosis-related genes ENPP2 and EPAS1 may increase HDM-induced AR risk and serve as potential predictors of HDM-induced AR susceptibility.

[Clinical features of systemic lupus erythematosus with pulmonary pleural lesion in children].

OBJECTIVE: To investigate the clinical features of systemic lupus erythematosus (SLE) with pulmonary pleural lesion in children. METHODS: One hundred and thirty three child patients with SLE admitted from 2001 to 2010 were enrolled in the study. The clinical data, chest X-ray findings and laboratory examination were retrospectively reviewed. Cases with infectious pulmonary pleural lesion were excluded. RESULTS: According to chest X-ray findings pleural pulmonary lesions were involved in 45 out of 133 cases with SLE (33.83 %); however, only 30 cases (66.67 %) had positive respiratory manifestations. Respiratory features included cough and/or sputum (55.56 %), dyspnea and chest pain (15.56 % and 11.11 %), and only 28.89 % case with pleural pulmonary lesions had rales. Chest X-ray findings included pleural effusion/pleurisy (32 cases, 71.11%), bronchial pneumonia (21 cases, 46.67%) or interstitial pulmonary disease (13 cases, 28.89%). Compared to children without pulmonary pleural lesion, children with pulmonary pleural lesion had higher incidence of leukopenia, lower C3 or antibody dsDNA (+) (all P<0.05). There was no difference in abnormality of erythrocyte sedimentation rate (ESR), CRP, IgG,IgA,IgM, thrombocytopenia, antibody ANA(+), anti-SSA(+), anti-SSB(+) or anti-Sm(+) between children with or without pulmonary pleural lesion (P>0.05). CONCLUSION: High incidence of pulmonary pleura lesions are present in children with SLE, however, clinical manifestations are lack of specificity or even no respiratory manifestation. Chest X-ray or HRCT scan are necessary in all cases with SLE. Children with leukopenia, lower C3 or antibody dsDNA (+) are more likely to have pulmonary pleural lesion.

TLR Signaling Pathway Gene Polymorphisms, Gene-Gene and Gene-Environment Interactions in Allergic Rhinitis.

Background: Allergic rhinitis (AR) is a nasal inflammatory disease resulting from a complex interplay between genetic and environmental factors. The association between Toll-like receptor (TLR) signaling pathway and environmental factors in AR pathogenesis remains to be explored. This study aims to assess the genetic association of AR with single nucleotide polymorphisms (SNPs) in TLR signaling pathway, and investigate the roles of gene-gene and gene-environment interactions in AR. Methods: A total of 452 AR patients and 495 healthy controls from eastern China were enrolled in this hospital-based case-control study. We evaluated putatively functional genetic polymorphisms in TLR2, TLR4 and CD14 genes for their association with susceptibility to AR and related clinical phenotypes. Interactions between environmental factors (such as traffic pollution, residence, pet keeping) and polymorphisms with AR were examined using logistic regression. Models were stratified by genotype and interaction terms, and tested for the significance of gene-gene and gene-environment interactions. Results: In the single-locus analysis, two SNPs in CD14, rs2563298 (A/C) and rs2569191 (C/T) were associated with a significantly decreased risk of AR. Compared with the GG genotype, the GT and GT/TT genotypes of TLR2 rs7656411 (G/T) were associated with a significantly increased risk of AR. Gene-gene interactions (eg, TLR2 rs7656411, TLR4 rs1927914, and CD14 rs2563298) was associated with AR. Gene-environment interactions (eg, TLR4 or CD14 polymorphisms and certain environmental exposures) were found in AR cases, but they were not significant after Bonferroni correction. Conclusion: The genetic polymorphisms of TLR2 and CD14 and gene-gene interactions in TLR signaling pathway were associated with susceptibility to AR in this Han Chinese population. However, the present results were limited to support the association between gene-environment interactions and AR.

GARP Polymorphisms Associated with Susceptibility to House Dust Mite-Sensitized Persistent Allergic Rhinitis in a Chinese Population.

Background: Genetic variants in GARP (also known as LRRC32) have been reported to have significant associations with asthma and eczema in special populations, but little is known about allergic rhinitis. This study purposes to evaluate the association of single nucleotide polymorphisms (SNPs) in GARP with house dust mite (HDM)-sensitized persistent allergic rhinitis (PER) in a population of Han Chinese. Methods: In this hospital-based case-control study, 534 HDM-sensitized PER patients and 451 healthy controls were recruited from East China. In this population, six SNPs in GARP were identified. Serum total and specific IgE levels were measured with ImmunoCAP. Secondary structure and minimum free energy were predicted by RNAfold. Results: rs79525962 was associated with the risk of HDM-sensitized PER (P < 0.05). The individuals with CT+TT genotype demonstrated a higher risk of HDM-sensitized PER than those with CC genotype (adjusted OR = 1.393, 95% CI = 1.019-1.904). The homozygous genotype CC of rs3781699 rendered a lower risk of HDM-sensitized PER than the wild-type genotype AA (adjusted OR = 0.646, 95% CI = 0.427-0.976); however, the genotype and allele frequencies of rs3781699 demonstrated no associations with HDM-sensitized PER (P > 0.05). rs79525962 increased the risk of HDM-sensitized PER in the subgroup aged ≥16 years (adjusted OR = 1.745, 95% CI = 1.103-2.760), and this high risk was also found in the females (adjusted OR = 1.708, 95% CI = 1.021-2.856). The G-C haplotype of rs1320646-rs3781699 rendered a lower risk of HDM-sensitized PER than the common haplotype G-A (adjusted OR = 0.819, 95% CI = 0.676-0.993). The secondary structure of GARP altered in response to different genotypes of rs79525962 and rs3781699. Conclusion: SNP rs79525962 in the GARP gene marks a risk locus of HDM-sensitized PER in Chinese Hans.

Prevalence of Epstein-Barr virus infection and characteristics of lymphocyte subsets in newly onset juvenile dermatomyositis.

BACKGROUND: The underlying etiology of juvenile dermatomyositis (JDM) is unknown. T cell deficiency as well as Epstein-Barr virus (EBV) infection had been suspected to be involved in the pathogenesis, but it has been poorly evaluated in JDM patients. METHODS: This study described the traits of T and B lymphocyte subsets in newly onset JDM patients and the incidence of EBV infection in JDM patients compared with match controls. Newly developed JDM patients from 2014 to 2018 were included in the study. Lymphocytes with different markers (CD3+, CD3+CD4+, CD3+CD8+, CD3-CD19+ and CD3-CD16+CD56+) were tested with flow cytometry in the first admission or after 6 months of treatment. Statistical analysis was conducted to compare the EBV infection in the group of JDM patients and controls. RESULTS: We observed that JDM patients had higher positive rate of Epstein-Barr nuclear antigen-immunoglobulin G (IgG) (P < 0.0001) as well as EBV capsid antigen-IgG (P < 0.05) than normal controls. CD3-CD16+CD56+ lymphocyte was found to be extremely low in early stage of JDM patients, but increased after 6 months of treatment (P = 0.0091). CONCLUSIONS: The level of CD3-CD16+CD56+ cells may associate with the clinical course of JDM. EBV may act as an environmental factor predisposing patients to the development of JDM.

CircRNA expression profiles and circRNA-miRNA-mRNA crosstalk in allergic rhinitis.

BACKGROUND: Circular RNAs (circRNAs) are involved in inflammation; however, their role in allergic rhinitis (AR) remains unclear. In this study, we analyzed circRNA expression and identified a circRNA-miRNA-mRNA network through which circRNAs regulate AR pathogenesis. METHODS: We analyzed circRNA, miRNA, and mRNA expression profiles in the nasal mucosa by high-throughput sequencing (HTS), using a fold-change >1.5 and p-value < 0.05 to pinpoint significantly differentially expressed (DE) circRNAs, miRNAs, and mRNAs in AR. A DEcircRNA-DEmiRNA-DEmRNA crosstalk network was then constructed using bioinformatics and statistical analysis. Gene ontology and Kyoto encyclopedia of genes and genomes pathway analyses were performed to identify the biological terms enriched in the network; whereas RT-PCR and Sanger sequencing were used to confirm the circRNAs. RESULTS: A total of 264 DEcircRNAs were identified by HTS, including 120 upregulated and 144 downregulated in AR compared to controls. A DEcircRNA-DEmiRNA-DEmRNA crosstalk network was constructed with 17 miRNAs, 11 circRNAs, 29 mRNAs, and 64 interaction pairs. These genes were involved in the Wnt signaling pathway, TNF biosynthesis, inflammatory responses, the PI3K-Akt signaling pathway, and Toll-like receptors. Of the 11 DEcircRNAs, hsa_circ_0008668 and circTRIQK were upregulated, whereas hsa_circ_0029853 and circRNA_01002 were downregulated in AR tissues. Sanger sequencing confirmed the back-splicing junctions of these circRNAs. CONCLUSIONS: We constructed a novel DEcircRNA-DEmiRNA-DEmRNA network for AR that provides a basis for future studies to investigate its underlying molecular mechanisms.

Genetic variants in Hippo pathway genes are associated with house dust mite-induced allergic rhinitis in a Chinese population.

BACKGROUND: House dust mite (HDM)-induced allergic rhinitis (AR) is a highly prevalent disease with bothersome symptoms. Genetic variants of the Hippo pathway genes play a critical role in the respiratory disease. However, no study has reported associations between variants of the Hippo pathway genes and HDM-induced AR risk. METHODS: Forty-three key genes in the Hippo pathway were selected from the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome pathway database, and previous reported studies. A case-control study of 222 cases and 237 controls was performed to assess the associations between 121 genetic variants in these genes and HDM-induced AR risk. DNeasy Blood & Tissues Kits were used for extracting genomic DNA from the venous blood and Infinium Asian Screening Array BeadChips for performing genotyping. A logistic regression model was applied to evaluate the effects of variants on HDM-induced AR risk. The false discovery rate (FDR) method was utilized to correct for multiple testing. The receiver operating characteristic (ROC) curve was plotted to obtain the cut-off value of total IgE for the diagnosis of HDM-induced AR. Histone modification and transcription factor binding sites were visualized by UCSC genome browser. Moreover, expression qualitative trait loci (eQTL) analysis was obtained from Genotype-Tissue Expression (GTEx) database. RESULTS: We found that rs754466 in DLG5 was significantly associated with a decreased HDM-induced AR risk after FDR correction (adjusted odds ratio [OR] = 0.52, 95% confidence interval [CI] = 0.36-0.74, p = 3.25 × 10-4 , PFDR  = 3.93 × 10-2 ). The rs754466 A allele reduced the risk of HDM-induced AR in the subgroup of moderate/severe total nasal symptom score (TNSS). Furthermore, rs754466 was associated with a high mRNA expression of DLG5. Additionally, histone modification and transcription factor binding sites were rich in the region containing rs754466. CONCLUSION: Our findings indicated that rs754466 in DLG5 decreased the susceptibility to HDM-induced AR.

Juvenile dermatomyositis: advances in clinical presentation, myositis-specific antibodies and treatment.

BACKGROUND: Juvenile dermatomyositis (JDM) is a chronic autoimmune disease characteristic by inflammation of small vessels within the skin, muscle and vital organs. But the clinical features and treatment of JDM have not been fully clarified. DATA SOURCES: Databases underwent through PubMed for articles about the clinical features, myositis-specific antibodies of JDM and its treatment, and we selected publications written in English which were relevant to the topic of this review. RESULTS: Clinical features and myositis-specific antibodies may predict the severity and prognosis of disease. Although the mortality rate has been lower with traditional treatments, such as corticosteroid, intravenous immunoglobulin, and disease-modifying anti-rheumatic drugs such as methotrexate, their usages are variable. Novel biological therapies seem to be effective for refractory JDM patients, but more clinical trials are necessary. CONCLUSIONS: JDM is a sever disease of childhood. We need to better understand recent advances of JDM in the context of clinical features including skin manifestations, muscle weakness and organ damage, myositis-specific antibodies and their associated outcomes and the treatment of disease.

Current status and recent advances on the use of ultrasonography in pediatric rheumatic diseases.

BACKGROUND: Ultrasonography has become a useful tool in the clinical rheumatology settings in the last two decades, but its use has only recently been explored by pediatric rheumatologists. The aim of this article is to review the literature on the current status and recent advances on the use of ultrasound in pediatric rheumatic diseases. DATA SOURCES: We have retrieved and reviewed the relevant articles from MEDLINE/PubMed databases published so far, on the applications of ultrasound in juvenile idiopathic arthritis (JIA), systemic lupus erythematosus, dermatomyositis, enthesitis, Sjogren's syndrome, and other rheumatic diseases. In addition, articles on novel ultrasound imaging technology of potential use in pediatric rheumatology are also reviewed. RESULTS: In JIA, ultrasound can be used to detect subclinical synovitis, to improve the classification of patients in JIA subtypes, to capture early articular damage, to monitor treatment response, and to guide intraarticular injections. Ultrasound is also considered useful in other rheumatic disorders for the evaluation of musculoskeletal symptoms, assessment of parotid gland pathology, and measurement of skin thickness and pathology. Novel ultrasound techniques developed to augment the functionality of ultrasonography may also be applicable in pediatric rheumatic disorders. CONCLUSIONS: Ultrasound shows great promise in the assessment and management of children with rheumatologic disorders. However, standardization and validation of ultrasound in healthy children and in patients with rheumatic diseases are still needed.