Diagnostic Performance Of 14-3-3? For Rheumatoid Arthritis And The Potential Mechanism Associated With Osteoporosis In RA Patients

Background:Rheumatoid arthritis(RA)is a clinically common chronic inflammatory disease mediated by autoimmunity.At present,the pathogenesis of the disease and the specific pathogenesis have not yet been elucidated,and there is no effective treatment to reverse RA.Early diagnosis and timely treatment are the top priorities of RA disease management.Rheumatoid factor(RF)and anti-cyclic citrullinated peptide antibody(anti-CCP)are representative hallmarks of RA utilized in clinical practice.However,RA has a variety of manifestations,and atypical cases are difficult to distinguish from other inflammatory joint lesions,leading to misdiagnosis of some patients and missing the best treatment opportunity.Therefore,it is a hot research topic to find serological indicators more sensitive and specific to improve diagnostic rate as well as to explore the etiology and pathogenesis of RA.Studies have shown that 14-3-3? elevated in serum of RA patients,and had certain value in the disease diagnosis and monitoring.Clinical significance of 14-3-3? detection in RA and its specific role in the development of RA has rarely been reported.Objective:The aim of the present study was to clarify the diagnostic performance of 14-3-3? for RA and its association with RA-related osteoporosis.As well as to explore the potential mechanism of 14-3-3? protein involved in RA pathogenesis.Methods:The current study enrolled 160 definitely diagnosed RA patients,153 non-RA disease controls and 60 healthy subjects with 14-3-3? levels detected by ELISA.Receiver operating characteristic(ROC)curve was conducted to determine diagnostic value of 14-3-3? alone and its combination with other indicators for RA.The association between 14-3-3? and osteoporosis in RA patients was analyzed by binary Logistic regression.In addition,FLS was stimulated with recombinant 14-3-3? protein,and the expression of MMP-1 was determined by real-time fluorescence quantitative PCR(qPCR).Results:(1)14-3-3? protein in the RA group,healthy controls and non-RA controls were 3.19(1.94-5.05)ng/ ml,0.31(0.16-1.67)ng/ml and 1.13(0.57-1.87)ng/ml respectively,there was a significant difference among groups,P=0.013.(2)When cutoff was 2.60 ng/ml,the sensitivity and specificity of 14-3-3? to diagnose RA were 63.33% and 94.12%,respectively,with moderate value.14-3-3? combined with anti-CCP can improve the diagnostic level of RA.(3)Levels of serum 14-3-3? in patients with osteoporosis and osteopenia were higher than that in patients with normal bone mass.Logistics regression analysis showed that 14-3-3? was associated with osteoporosis and osteopenia in RA patients(P<0.05).(4)qPCR showed that recombinant 14-3-3? protein can stimulate FLS to increase the expression of MMP-1.Conclusion:The present study,from clinical and molecular levels,investigated the clinical significance of 14-3-3? detection in RA and its potential molecular mechanisms involved in the pathogenesis of RA.Levels of 14-3-3? elevated in the serum of RA patients and can be used as a reference for its diagnosis.And 14-3-3? was associated with osteoporosis occurance in RA patients and can be used for disease monitoring clinically.Stimulating FLS with recombinant 14-3-3? can increase its expression of MMP-1,which provides a new idea for the pathogenesis of RA.