| Objective: Rheumatoid is a group diseases,which widely damage to many organs.The damage is inflammation or non-inflammation.Rheumatoid arthritis(RA)is one of rheumatoid which can damage several tissue and organs.The main clinical manifestation is symmetric multiple swelling and pain with peripheral joint.In early stage if they are not diagnosis and intervened,the advanced damage of bone and joint will lead to malformation.Because rheumatoid arthristis is an autoimmune diseases with no explained reason,there is no biomarker to diagnosis.At present,limited by the sensitivity and specificity of the laboratory indicators,there is many misdiagnosis with negative laboratory results,so it is important to find new indicators to help RA.14-3-3 protein was discovered in 1967 by Moore and Perez.It is a highly conserved protein family.Almost it existed in all eukaryotic cells.There was seven isoforms.It conjoints with many intracellular proteins to take part in the biological processes.It is an signal protein to adjust biological processes which include cell division,apotosis,signal transduction,transmembrane action,and so on.At beginning studies,14-3-3 protein was researched in nerve system.In 2007,it was the first time to be discovered by Ghahary.Immunoblot experiments of both the synovial fluid and serum of patients with inflammatory arthritis using keratinocyte lasate as a positive control revealed the present of two isoforms of 14-3-3 protein,γ andη,with the latter being the predominant isoform based on mass spectrometry data.Levels of 14-3-3 protein were up to 5 times higher in synovial fluid than that in matched serum,indicating that the synovium is the likely source of this biomarker.And both serum and synovial levels of 14-3-3η protein correlated highly with levels of MMP-1 and MMP-3.It showed that there is a most possible relationship between 14-3-3η and joint damage.A small number of research found that 14-3-3η protein took part in the pathogenesis machine of RA,and the relation of diseases activity,diagnosis and prognosis of RA.There is little studies on the relationship between 14-3-3η protein and RA in literature.The purpose of this study is to detect the 14-3-3η protein levels in serum with RA,and detect anti-CCP,RF,CRP,ESR,to provide better marker for the diagnosis and treatment of patients with RA.Methods: 1.Subjects: ninety-four patients who were diagnosed with RA entered the study,all patients fulfilled the ACR(formerly ARA)1987 revised criteria and 2010 new criteria by ACR and EULAR for the classification of RA.Their disease durations last from twelve months to sixty months.They had not been treated by disease modifying antirheumatatic drug(DMARDs)before diagnosed with RA.The group of disease control including osteoarthritis(OA)、 ankylosing sporidylitis(AS)and gout was consisted of forty cases.Forty healthy individuals from the health center were selected as health controls,all subjects were excluded by long term with estrogen,androgen,anticoagulant,bone metabolism drugs,severe damage with heart,lung,liver,kidney etc;disease on thyroid and parathyroid;women with lactation and gestation;smokers.2.To evaluate the diagnostic performance of 14-3-3η protein to RA: Detected 14-3-3η protein in patients with RA,OA,AS,gout and the healthy controls,Which included 14-3-3η protein,the rheumatoid factor(RF).and anti-cyclic citrullinated peptides(anti-CCP).Used by receiver operating characteristic curve(ROC),the diagnostic value for RA were evaluated.3.To evaluate 14-3-3η protein in predicting disease,disease activity and curative effect: Association between 14-3-3η protein and X-ray stage were evaluated in RA using a rank correlation test.14-3-3η and indexes of disease activity were detected in patients with RA in order to analyze their clinical significance.Results: 1.Diagnostic value of 14-3-3η protein: When RF≥30 IU/m L,anti-CCP>12 RU/m L and 14-3-3η protein≥1.44 ng/m L served as thresholds for RA diagnosis,14-3-3η protein in the diagnosis of RA the area under the ROC was 0.81,the sensitivity,specificity and accuracy was 78.7%,and 73.8%,respectively.The levels of the 14-3-3η,anti-CCP and RF in groups of RA were higher than that of OA,AS,gout and healthy control(P<0.001).2.To evaluate the clinical significance of the 14-3-3η protein in predicting the prognosis,curative effect and activity: RF and disease duration of RA was significantly associated with X-ray stage(r =0.303,P<0.01,r =0.623,P<0.001).The levels of 14-3-3η protein of RA was significantly associated with CRP(r=0.250,P<0.05),ESR(r=0.294,P<0.01).,DAS(r=0.275,P<0.05)..3.With different combination,the sensitivity in diagnosis of the RA of combining the detection 14-3-3η protein with RF and anti-CCP was 98.9%.the specificity was 98.75%.Conclusions: 1.14-3-3η has a high value in diagnosis RA.Particularly the value of combining the detection of RF with 14-3-3η protein,14-3-3η protein with Anti-CCP will improve sensitivity in diagnosis of the RA.The value of 14-3-3η can identify RA patients from OA and AS patients.2.14-3-3η protein,anti-CCP antibodies and RF were useful indexes in predicting the prognosis of RA patients.The 14-3-3η protein showed association with disease activity and curative effect.3.14-3-3η protein covers the shortage of RF and anti-CCP to diagnosis RA. |
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