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Comparisons Of Biomarkers Between Psoriasis And Atopic Dermatitis In Chinese Population

Posted on:2021-01-24Degree:DoctorType:Dissertation
Country:ChinaCandidate:J W ChenFull Text:PDF
GTID:1484306503985369Subject:Dermatology and Venereology
Abstract/Summary:PDF Full Text Request
PART ? IDENTIFICATION OF A TH2-HIGH PSORIASIS CLUSTER BASED ON SKIN BIOMARKER ANALYSIS IN A CHINESE PSORIASIS POPULATIONBackground:Psoriasis is an immune-mediated,chronic inflammatory disease with diverse phenotypes.However,its biological diversity has not been well-characterized in Chinese psoriasis population.Objective:To characterize psoriasis biological heterogenicity using gene expression profiles of lesional skin biopsy specimens in a Chinese psoriasis population.Method:Lesional tissues and blood samples from Chinese psoriasis patients(n=40),atopic dermatitis(AD)patients(n=25)and age-matched healthy controls(n=19)were investigated by using Real-Time PCR Array,histological evaluation and flow cytometry.Unsupervised hierarchical clustering was performed using gene expression profiles of patients with psoriasis.Results:Two distinct psoriasis clusters were identified.Both clusters indicated high T_H17 activation.One cluster(n=6 of 40 consecutive psoriasis patients)indicated a strong T_H2 component in skin lesions,with early onset and low peripheral blood eosinophil level.Significantly higher IL-4,IL-13,IL-25,IL-31 and TSLP gene induction typified this cluster of psoriasis patients,even compared with AD patients.Both psoriasis clusters were characterized by neutrophilic microabscess formation.Histologically,the T_H2 high psoriasis cluster indicated a low percentage of perivascular eosinophils.In addition,Chinese AD patients indicated high T_H17/T_H22activation,while a reduction of some T_H2 components.Conclusion:Two distinct psoriasis clusters were identified.One presented early onset and a low eosinophil level,indicating T_H17 polarization and a strong T_H2 component.These results laid the foundation for further demonstrating the pathogenesis of psoriasis in Chinese population.PART ? DISTINCT CLINICAL AND MOLECULAR PHENOTYPES IN PSORIASIS PATIENTS WITH AND WITHOUT DERMAL EOSINOPHILIC INFILTRATIONBackground: Recent studies have demonstrated that eosinophils participate in the pathogenesis of psoriasis.Objectives: To investigate the different clinical characteristics and lesional gene expression profiles of psoriasis patients with and without dermal eosinophilic infiltration(EI).Method: A total of 40 patients diagnosed with psoriasis vulgaris were divided into two groups based on the presence of dermal EI.Tissue and blood samples of the patients and healthy controls(n=19)were subjected to histological analysis,real-time polymerase chain reaction analysis,and flow cytometry.Result: EI was present in 42.5%(17/40)of specimens with 17.5%(7/40)judged as rare,12.5%(5/40)as moderate,and 12.5%(5/40)as dense.There was no significant difference in other histopathological features.Psoriasis patients with EI had higher serum Ig E levels,peripheral blood eosinophils count,and levels of IL-4 produced by peripheral blood CD3~+ CD4~+ T cells.More patients without EI had a family history of psoriasis(p = 0.068).There were differences in the expression levels of TH17 markers between the two groups.The expression levels of S100A8,PI3,and IL-36 G were higher,while those of EBI3,IL-19,HBD3 were lower in patients with EI.Psoriasis patients with EI had significantly lower levels of some TH2/TH9-related genes(IL-9,IL-31,OX40,OX40 L,CCL17,and CCL22)in skin lesion.Conclusion: The presence of dermal EI influenced the clinical characteristics and molecular phenotypes of patients with psoriasis.A TH2-independent pathway was speculated to activate eosinophils,leading to the promotion of neutrophils in the pathogenesis of psoriasis.
Keywords/Search Tags:psoriasis, atopic dermatitis, T_H2, T_H17, cluster analysis, onset age, eosinophil, neutrophil
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