Clinical Studies Of Serum Syndecan-4 In The Diagnosis Of Rheumatoid Arthritis And Disease Activity

Research Background:Rheumatoid arthritis(RA)is a chronic autoimmune disease with a complex pathology and a diverse clinical presentation,mainly resulting in joint inflammation,but also affecting other systems such as the skin and heart.Long-term chronic inflammation of the joints can lead to deformities and even disability,and this change is often irreversible.In clinical practice,the initial diagnosis of RA is based on clinical symptoms and laboratory tests such as rheumatoid factor(RF),but the differential diagnosis of RA from other joint diseases and other autoimmune disorders is still difficult.In particular,when the clinical presentation of RA is atypical,it can be easily confused with other arthritis-related diseases or other autoimmune diseases,which may lead to misdiagnosis and miss the best time for treatment.In recent years,it has been found that the multiligand proteoglycan-4(SDC-4)was involved in the pathogenesis of RA,mediating mitogen-activated protein kinase(mitogen-activated protein kinase,MAPK)signalling and was aberrantly expressed in the synovial fibroblasts of the disease.SDC-4 stabilises the interaction between growth factors and other cell membrane receptors to form ligand-heparin-receptor complexes.SDC-4 has been found to affect endothelial cell migration and proliferation through regulation of the protein kinase alpha(PKCα)and extracellular signal-regulated kinase 1/2(ERK1/2)signaling pathways.Currently,disease activity in RA is usually assessed clinically using the Disease Activity Score 28(DAS28),which consists of a composite analysis of the number of tender joints(TJC),the number of swollen joints(SJC),the Patient General Assessment(PGA)and the Visual Analogue Scale(VAS)100mm.However,evaluation by the DAS28 is highly subjective(different assessors can produce widely varying results)and lagging.Finding accurate indicators that can objectively assess disease activity and early diagnosis is therefore a pressing challenge at this stage.Objective:To investigate the clinical value of serum SDC-4 and autoantibodies in the diagnosis of RA and assessment of disease activity.Methods:In this study,141 cases of RA,250 cases of non-RA(non-RA)and 60 healthy controls(HC)from a large general tertiary hospital in Jiangxi were selected.The serum SDC-4 was measured by ELISA;the anti-cyclic citrullinated peptide antibody(anti-CCP)was measured by chemiluminescence(i Flash 3000-C Chemiluminescent Immunoassay Analyze)r;RF,Anti-streptococcal haemolysin"O"(ASO)and C-reactive protein(CRP)were measured by immunoscattering turbidimetry using the IMMAGE800 specific protein analysis system.The Roller 20r of automatic rapid blood sedimentation analyzer was used to measure ESR by using the Weil’s method.To plot the operating characteristic curve(ROC)for each indicator.The above indicators and clinical information such as TJC,SJC and Patient General Assessment(PGA)were analyzed using Spearman correlation.Analysis of the variability of SDC-4 levels in patients with different levels of active RA.Results:1.The results of theχ~2test and ANOVA showed no statistically significant differences(P>0.05)between the 3 groups of RA,non-RA and HC in terms of gender and age.Statistical analysis showed that the levels of SDC-4,anti-CCP,RF and ESR in the RA,non-RA and HC groups were 1272.65±718.19 pg/ml,757.11±422.30 pg/ml and 385.44±90.85 pg/ml respectively.were significantly higher than those of non-RA and HC,with statistically significant differences(P<0.01);in the non-RA group serum ASO levels were significantly higher than those of RA and HC,with statistically significant differences(P<0.01).2.The ROC curve evaluated the diagnostic value of serum SDC-4,anti-CCP,RF,ASO,ESR and CRP for RA.The results showed that the Cut-off values were 967.32pg/ml,120.90 U/ml,62.51 IU/ml,130.31 IU/ml,33.10 mm/h and 15.13 mg/l,respectively,The highest AUC was for anti-CCP(0.93),which was of high diagnostic value;the AUCs for SDC-4 and RF were 0.79 and 0.82,respectively,which were of moderate diagnostic value;the AUCs for ASO,ESR and CRP were 0.52,0.59 and0.51,respectively,which were of low diagnostic value.3.The analysis of SDC-4,anti-CCP,RF,ASO,ESR and CRP serum levels for the clinical evaluation of RA showed that the specificity of each index was 87.74%,94.84%,69.35%,60.00%,54.84%and 57.10%,in that order.The highest specificity for the diagnosis of RA was with anti-CCP;SDC-4 was second only.4.Parallel analysis showed that the combination with the highest YDI was SDC-4/anti-CCP,which corresponded to a sensitivity and specificity of 89.16%and 83.21%,respectively.The highest YDI combination was anti-CCP/RF,with a sensitivity and specificity of 53.18%and 98.42%,respectively.5.Spearman’s correlation analysis of serum SDC-4 with anti-CCP and RF etc.in the RA group:the results showed that the correlation coefficients between serum SDC-4 and RF,CRP,SJC,PGA、DAS28 were 0.41,0.26,0.38,0.37,0.23respectively,with statistically significant differences(P<0.01).6.When comparing the RA-active group,RA-stable group and HC serum SDC-4 levels,there was no statistically significant difference between the three groups in terms of age and gender(P>0.05).The RA-active,RA-stable and HC serum SDC-4levels were compared by ANOVA,with RA-active being higher than RA-stable and HC,and RA-stable also being higher than HC,and all differences were statistically significant(P<0.01).7.Serum SDC-4 levels were compared by ANOVA between highly active RA(H-active),moderately active RA(M-active)and low active RA(L-active),with H-active being higher than the moderately active group and M-active being higher than L-active,and all differences were statistically significant(P<0.01).8.The ROC curve evaluated the diagnostic value of serum SDC-4,anti-CCP,RF,ASO,ESR and CRP for active RA.The results showed that the Cut-off values were610.92 pg/ml,853.51 U/ml,29.33 IU/ml,134.72 IU/ml,30.15 mm/h and 13.31 mg/l,respectively,The AUCs of SDC-4 and CRP were 0.93 and 0.92,respectively,which were high diagnostic levels;the AUCs of anti-CCP,RF and ESR were 0.85,0.89 and0.89,respectively,which were moderate diagnostic levels;and the AUC of ASO was0.52,which was of low diagnostic value.Conclusion:1.increased levels of serum SDC-4 in RA patients have a high diagnostic value;2.serum SDC-4 in combination with other indicators such as anti-CCP and RF may improve the differential diagnosis of RA and other diseases;however,ASO is of low diagnostic or differential value in the diagnosis of RA;3.serum SDC-4 levels can provide a basis for assessing the disease activity of RA;4.serum SDC-4,anti-CCP and RF tests can provide a better experimental basis for clinical treatment of RA.