Prediction of clinical efficacy of subcutaneous immunotherapy for Artemisia sieversiana pollen allergic rhinitis by serum metabolomics.

BACKGROUND/PURPOSE: Specific immunotherapy is the only effective etiological treatment for allergic rhinitis, but subcutaneous immunotherapy has a slow onset and poor compliance. Predicting the clinical efficacy of subcutaneous immunotherapy in advance can reduce unnecessary medical costs and resource waste. This study aimed to identify metabolites that could predict the efficacy of subcutaneous immunotherapy on seasonal allergic rhinitis by serum metabolomics. METHODS: Patients (n = 43) with Artemisia sieversiana pollen allergic rhinitis were enrolled and treated with subcutaneous immunotherapy for one year. Patients were divided into the ineffective group (n = 10) and effective group (n = 33) according to the therapeutic index. Serum samples were collected before treatment. Metabolomics was determined by liquid chromatography-mass spectrometry combined with gas chromatography-mass spectrometry and analyzed differential compounds and related metabolic pathways. RESULTS: A total of 129 differential metabolites (P < 0.05) were identified and 4 metabolic pathways, namely taurine and hypotaurine metabolism, pentose and glucuronate interconversions, pentose phosphate pathway, and alanine, aspartate, and glutamate metabolism, were involved. CONCLUSION: Some metabolites, such as hypotaurine, taurine, and l-alanine, have the potential to become predictive biomarkers for effective subcutaneous immunotherapy.

Leukotriene A4 Hydrolase Is a Candidate Predictive Biomarker for Successful Allergen Immunotherapy.

Background: Allergic rhinitis is a common disorder that affects 10% to 40% of the population worldwide. Allergen immunotherapy (AIT) represents the only therapy that has the potential to resolve clinical symptoms of allergic rhinitis. However, up to 30% of patients do not respond to AIT. Biomarkers predicting the clinical efficacy of AIT as early as possible would significantly improve the patient selection and reduce unnecessary societal costs. Methods: Artemisia pollen allergic patients who received at least 1-year AIT were enrolled. Clinical responses before and after 1-year AIT were evaluated to determine AIT responders. Artemisia specific IgE and IgG4 levels were measured by using ImmunoCAP and enzyme-linked immunosorbent assay (ELISA) separately. Stepwise regression analysis was performed to identify which rhinitis-relevant parameters explained the most variability in AIT results. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics was applied to identify the potential candidate biomarkers in the sera of responders and non-responders collected before and after 1-year therapy. The diagnostic performance of the potential biomarkers was then assessed using enzyme-linked immunosorbent assay (ELISA) in 30 responders and 15 non-responders. Results: Artemisia specific IgE and IgG4 levels were elevated only in the responders. Regression analysis of allergic rhinitis-relevant parameters provided a robust model that included two most significant variables (sneeze and nasal congestion). Thirteen candidate biomarkers were identified for predicting AIT outcomes. Based on their association with allergy and protein fold change (more than 1.1 or less than 0.9), four proteins were identified to be potential biomarkers for predicting effective AIT. However, further ELISA revealed that only leukotriene A4 hydrolase (LTA4H) was consistent with the proteomics data. The LTA4H level in responders increased significantly (P < 0.001) after 1-year therapy, while that of non-responders remained unchanged. Assessment of LTA4H generated area under curve (AUC) value of 0.844 (95% confidence interval: 0.727 to 0.962; P < 0.05) in distinguishing responders from the non-responders, suggesting that serum LTA4H might be a potential biomarker for predicting the efficiency of AIT. Conclusion: Serum LTA4H may be a potential biomarker for early prediction of an effective AIT.

Clinical Efficacy Evaluation of 1-Year Subcutaneous Immunotherapy for Artemisia sieversiana Pollen Allergic Rhinitis by Serum Metabolomics.

Subcutaneous immunotherapy is the only treatment that improves the natural progression of allergic rhinitis and maintains long-term outcomes after discontinuation of the drug. Metabolomics is increasingly applied in the study of allergic diseases, including allergic rhinitis. However, little is known about the discovery of metabolites that can evaluate clinical efficacy and possible mechanisms of Artemisia sieversiana pollen subcutaneous immunotherapy. Thirty-three patients with Artemisia sieversiana pollen allergic rhinitis significantly improved after 1-year subcutaneous immunotherapy treatment, while ten patients were ineffective. Pre- and post-treatment serum samples from these patients were analyzed by metabolomics based on the combined detection of liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. As a result, L-Tyrosine can be a potential biomarker because of its opposite trend in effective patients and ineffective patients. And mechanism of immunotherapy may be closely related to NO and nitric oxide synthase. The discovery of potential biomarkers and metabolic pathways has contributed to the in-depth study of mechanisms of subcutaneous immunotherapy treatment of Artemisia sieversiana pollen allergic rhinitis.

[The contrastive study on lip profile of malocclusion of Class I, II and II in Harbin].

OBJECTIVE: To get reference for the diagnosis design and the clinical diagnosis, the difference is compared among lip profile on malocclusion of Class I, II and III from patients in Harbin, and the relationship is established between the linear cephalometric measurements and the regional cephalometric measurements. METHODS: 120 female patients, 18-25 years old, were selected. According to the value of / ANB which was measured on the pre-treatment cephalographs, they were divided into three groups--Class I, II and III. Each group had 40 patients. Each patient had the same type of skeletal pattern and occlusion pattern, and then 21 lip soft tissues were measured. Finally, the results of measurements were statistically analyzed with ANOVA and were compared between members in each group via SPSS 13.0 software. RESULTS: The differences among patients with lip profile on malocclusion had statistic significances (P < 0.05). In order of Class II, I and III, the UL-E, ULP, ULP-LLP, Sn-Ns-B' and S4 were progressively decreased and the B'-LL-FH, S-Ns-B' and S1 were increased. In order of Class II, III and I, the LL-B'-Pos and Z-angle were raised and LL-E was reduced. The length of the upper lip and the lower lip had no statistic significance (P > 0.05). CONCLUSION: There is difference among the Class I, II and III. The lip covering area is inclined to decrease the changes of the upper lip and increase the changes of the lower lip progressively with the variation of skeletal patterns in order of Class II, I, and III. Moreover, the condition of lip tissues can be accurately presented by the regional cephalometric measurements.