Pharmacoproteomic Study For Psoriasis Patients With Methotrexate Therapy

Psoriasis is one of chronic inflammatory-immune skin diseases.It has a chronic relapsing course,and is hard to radical cure.Psoriasis is clinically classified in four groups:psoriasis vulgaris,psoriasis pustulose,erythrodermic psoriasis,and psoriasis arfhropathica.Meanwhile,psoriasis vulgaris is the most commonly reported one among these clinical disease types,which takes almost 90% of psoriasis patients.Methotrexate(MTX),which was approved by the U.S.Food and Drug Administration(FDA)in 1971,has been used to treat severe psoriasis.Methotrexate has the rapid clearance in treating severe psoriasis,but unfortunately it cannot prevent recurrence.And 20% of patients’ response is moderate to poor.MTX is the inhibitor of dihydrofolate reductase,so it can suppress nucleic acid metabolism and cause chronic toxicity,especially liver toxicity.Thus,it is important to pay attention to use MTX towards psoriasis patients.With the development of mass spectrometry technology,high sensitivity and resolution instrument-based proteomic approach is applied to the clinical research to accelerate personalized medicine.In this study,quantitative proteomics approach based on chemical labeling is used to study the proteins expression level of peripheral blood mononuclear cell from psoriasis vulgaris patients treated with methotrexate.This work expects to find the molecular markers,which can guide the clinical application of methotrexate and may be prejudge the curative effect,to realize individualized treatment in combination with clinical data.In this study,we chose 20 PBMC samples from 4 cases of good responders(0 and 8 weeks),4 cases of no responders(0 and 8 weeks)to MTX treatment,and 4 cases of normal people without MTX.And we took the 20 PBMC samples in vitro labeling quantitative isotope labeling strategies,iTRAQ.We identified 3397 proteins and quantified 3190 proteins in 5 groups from 20 clinical samples.A set of proteins were selected based on bioinformatics analysis,and these proteins expression profiles are changed and can be recovered to normal level after MTX therapy only in good responding patients.In our preliminary validation of the ANXA6,it shows that the patients with highly specific expression of ANXA6 have good response in the treatment of MTX patients with remarkable feedback.In this work,for the first time we use the quantitative proteomic techniques associated with drug proteomic in PBMC cell of the psoriatic patients,and we found a set of proteins related to the action mechanism of MTX.This research can provide new clues to study the mechanism of clinical medicine,and provide certain clinical guidance to prognosis MTX therapy.