Observation Of The Efficacy Of Short-term Low-dose Glucocorticoids Therapy For Progressive Vitiligo And Screening And Verification Of Predictive Biomarkers

BackgroundVitiligo is a common acquired depigmentation disease,with the prevalence of 0.1%-2.7%in China.The etiology and mechanism of vitiligo remains unclear.Systemic glucocorticoids are recommended to prevent the progress of vitiligo,but there is lack of unified treatment consensus.The effectiveness and safety of previous glucocorticoids treatment strategies are various.There is an urgent need for a better glucocorticoids treatment strategy in clinic.In addition,there is no objective and effective biomarker that can predict and evaluate the efficacy of systemic glucocorticoids in the treatment of progressive vitiligo.Objective1.To propose an improved short-term low-dose systemic glucocorticoids therapy for progressive vitiligo.2.To screen and verify urinary biomarkers that can predict and evaluate the efficacy of systemic glucocorticoids therapy in progressive vitiligo patients.Method1.319 progressive vitiligo patients who met the criteria were enrolled.Patients were prescribed with oral prednisolone 0.5mg/kg/d for one week,and then gradually tapered in 5 weeks.Patients with stable or improved lesions stopped prednisolone and immunomodulator was prescribed.Paients with progressive lesions were prescribed with oral methylprednisolone 0.5mg/kg/d,and then gradually tapered in 5 weeks.A follow-up visit was conducted every 2 months for a total of 6 months.Efficacy and safety between different types of vitiligo,age groups and disease severity were evaluated.2.58 patients with progressive non-segmental vitiligo were included.Urine samples were collected before and after systemic glucocorticoids treatment.Patients were classified into treatment-effective group(n=42)and treatment-resistance group(n=16)based on the treatment efficacy.Each group was further divided into discovery cohort and validation cohort for proteomic analysis.Differential protein expression profiles between groups were identified and verified.Signal pathway analysis was conducted.Biomarkers that can be used to predict and monitor the efficacy of glucocorticoids therapy were preliminarily screened.3.The urine of patients with progressive non-segmental vitiligo before and after glucocorticoids treatment and healthy control group were collected.The selected biomarkers were verified by PRM and ELISA,and the diagnostic abilities were analyzed.Result1.The improved short-term low-dose glucocorticoids therapy can quickly halt the disease progression in all age groups and all types of progressive vitiligo,and the total effective rate is 88.71%.The treatment response is related to the severity of the disease(p=0.007).The therapy has minimal drug-related adverse events and high patient satisfaction.2.Before glucocorticoids treatment,245 differentially expressed proteins between treatment-effective group and treatment-resistance group were found,and 80 differentially expressed proteins were verified in the urine of progressive non-segmental vitiligo patients.341 differentially expressed proteins were found,and 54 differentially expressed proteins were verified after glucocorticoid treatment.By signaling analysis of differential expressed proteins,several signaling pathways related to pathogenesis of glucocorticoid resistance and the vitiligo were enriched.3.The increase level of urinary RBP-1 level and the decrease level of urinary TOR1AIP-1 could predict the efficacy of glucocorticoid treatment in patients with progressive vitiligo,with the AUCs of 1 and 0.875,respectively.The decrease level of urinary RBP-1 and the increase levels of urinary TOR1AIP-1 and urinary PDIA4 could evaluate the efficacy of glucocorticoid treatment in progressive vitiligo patients,with the AUCs of 0.8611,1 and 0.8681,respectively.ConclusionOur study proposed an improved short-term low-dose systemic glucocorticoids treatment strategy,which has good effectiveness and safety,and could be widely used in clinic.This study is the first time to use the urine of patients with progressive non-segmental vitiligo to screen and verify biomarkers that can objectively predict and monitor the effectiveness of glucocorticoids treatment by proteomic and immuological techniques,which will provide an important basis for guiding the individualized application of glucocorticoids in progressive vitiligo.