Identification of the E3 deubiquitinase ubiquitin-specific peptidase 21 (USP21) as a positive regulator of the transcription factor GATA3.

The expression of the transcription factor GATA3 in FOXP3(+) regulatory T (Treg) cells is crucial for their physiological function in limiting inflammatory responses. Although other studies have shown how T cell receptor (TcR) signals induce the up-regulation of GATA3 expression in Treg cells, the underlying mechanism that maintains GATA3 expression in Treg cells remains unclear. Here, we show how USP21 interacts with and stabilizes GATA3 by mediating its deubiquitination. In a T cell line model, we found that TcR stimulation promoted USP21 expression, which was further up-regulated in the presence of FOXP3. The USP21 mutant C221A reduced its capacity to stabilize GATA3 expression, and its knockdown led to the down-regulation of GATA3 protein expression in Treg cells. Furthermore, we found that FOXP3 could directly bind to the USP21 gene promoter and activated its transcription upon TcR stimulation. Finally, USP21, GATA3, and FOXP3 were found up-regulated in Treg cells that were isolated from asthmatic subjects. In summary, we have identified a USP21-mediated pathway that promotes GATA3 stabilization and expression at the post-translational level. We propose that this pathway forms an important signaling loop that stabilizes the expression of GATA3 in Treg cells.

Translation and validation of the Chinese version of Patient-completed Asthma Knowledge Questionnaire and its implementation in patient education.

Background: Poor control of asthma results from many factors, partly due to inadequate knowledge towards asthma among patients. It is necessary to know patients' knowledge level before education. However, there is no accepted instrument to evaluate knowledge of asthma in Chinese patients with asthma. The study aims to develop a Chinese version of Patient-completed Asthma Knowledge Questionnaire (PAKQ) to assess its reliability, validity, and responsiveness for testing its clinical application in Chinese adult patients with asthma. Methods: After translation, back-translation, and cross-cultural adaptation of the PAKQ into Chinese version, a survey of patients with asthma (n=464) in China was conducted. Demographics and clinical data were collected in addition to questionnaires concerning cognition of asthma, education, history, and asthma control test score. The PAKQ was then completed. 14±4 days after the initial assessment, the participants completed the retested questionnaire and again completed the questionnaire immediately after education. The reliability and the construct validity were evaluated. The optimal cut-off points for predicting disease knowledge among asthma patients were determined using the Youden index method. Results: The Chinese version of PAKQ showed high internal consistency (Cronbach's alpha =0.888) at baseline and an acceptable 2-week test-retest reliability (ICC =0.932, r=0.874). On the basis of large modification indices (>10), this four-factor questionnaire was found to fit the data satisfactorily (χ2/df =1.695, RMSEA =0.039, GFI =0.856, CFI =0.885, and SRMR =0.058). Paired t-tests showed significant changes on pre-educational and post-educational tests (t=22.83, df=463, P<0.0001). The optimal cut-off value of the PAKQ total score for assessing patients' knowledge level was 35 points (AUC =0.757). Conclusions: The Chinese version of the PAKQ questionnaire was developed and validated in terms of reliability and validity as an effective instrument for the insight into asthma knowledge of adult patients with asthma in China. Future research will evaluate the utility of the instrument in clinical practice.

[Clinical efficacy and safety of sublingual immunotherapy using standardized Dermatophagoides farinae extract for children with combined allergic rhinitis and asthma syndrome].

OBJECTIVE: To study the clinical efficacy of sublingual immunotherapy using standardized Dermatophagoides farinae extract for children with combined allergic rhinitis and asthma syndrome. METHODS: Fifty-two children, from 4 to 14 years of age, with mite-sensitive combined allergic rhinitis and asthma syndrome were treated sublingually with standardized Dermatophagoides farinae extract. The clinical efficacy was evaluated by monthly follow-up visits. After treatment for 1 or 2 years using the standardized Dermatophagoides farinae extract, the asthma and rhinitis symptom scores, medication scores and adverse reactions before and after treatment were evaluated. SPSS 17.0 software was used to analyze the data. RESULTS: The allergic asthma symptom scores before treatment during the day were 3.22 ± 0.66 and at night 2.05 ± 0.57. After 1 year of treatment, the day and night scores (1.68 ± 0.61, 0.94 ± 0.32) respectively, were decreased significantly (q values were 15.25 and 13.78 respectively, all P < 0.01). After 2 years of treatment, the scores (0.61 ± 0.28, 0.43 ± 0.13) were also decreased significantly (q values were 10.29 and 6.07 respectively, all P < 0.01). The allergic rhinitis symptom scores and medication scores were 2.34 ± 0.59 and 3.09 ± 1.01 respectively before treatment and 1.21 ± 0.46 and 1.89 ± 0.64 after 1 year of treatment. The differences were significant (q values were 15.48 and 18.61 respectively, all P < 0.01). The allergic rhinitis symptom scores and medication scores were 1.02 ± 0.37 and 1.49 ± 0.38 after 2 years of treatment. There was no significant difference between 2 years of treatment and 1 year of treatment (q values were 2.53 and 2.78 respectively, all P > 0.05). There were no severe adverse events during the treatment, except for mild mouth cavity discomfort. CONCLUSIONS: Sublingual immunotherapy using standardized Dermatophagoides farinae extract is safe and effective in the treatment of children with combined allergic rhinitis and asthma syndrome.