The Feasibility Study Of Soluble Lymphocyte-activation Gene 3 As A Potential Biomarker For Parkinson's Disease

ObjectiveThis study detected the serum lymphocyte-activation gene 3(sLAG3)levels in idiopathic Parkinson's Disease(PD),multiple system atrophy(MSA)and progerssive supranuelear palsy(PSP)patients,and investigated associations between sLAG3 and clinical parameters of PD.Evaluate whether sLAG3 can be a potential biological marker for diagnosis of PD.MethodsIdiopathic PD patients,age-matched probable MSA,PSP patients and controls(n=92,32,36 and 80,respectively)were enrolled.Fasting peripheral blood was obtained.For the PD subjects,the levodopa equivalent daily dose(LEDD)was calculated.The motor symptoms of PD was assessed by Movement Disorder Society-sponsored Revision of the Unified Parkinson's Disease Rating Scale(MDS UDPRS I-IV)and classified by Hoehn and Yahr Stage(H-Y stage)conducted during the off-medication phase.The non-motor symptoms of PD was evaluated according to Mini-mental State Examination(MMSE),Montreal Congnitive Assessment(MoCA),and Parkinson's Nonmoter Symptom Scale(NMSS).Define clinical subtypes according to the scores of MDS UPDRS-?.Serum sLAG3 levels were measured by human enzyme-linked immunosorbent assay(ELISA).Ordinal multi-class logistic regression analysis investigated correlations between sLAG3 and clinical parameters,including disease severity by the H-Y stage.Finally,receiver operating characteristic curve(ROC)was used to evaluate the diagnostic value of sLAG3.Results1.Comparison of serum sLAG3 levels in four groups? The serum sLAG3 levels of PD group(912.75±258.28 pg/mL)were significantly higher than control group(719.83±203.02 pg/mL,P<0.01).? The serum sLAG3 levels of PD group were significantly higher than PSP group(720.18±198.03 pg/mL,P<0.01).? The serum sLAG3 levels of the PD group were lower than MSA group(1094.62±329.15pg/mL,P<0.05),with statistically significance.2.Serum sLAG3 levels of men and women in PD groupThe serum sLAG3 levels in female PD patients(1040.30 ± 267.00 pg/mL)were significantly higher than male patients(790.62±180.62 pg/mL,P=0.012).3.Correlation between sLAG3 levels and clinical parameters in PD group? Spearman correlation analysis showed that the serum sLAG3 level was significantly correlated with gender(r = 0.426,P<0.001)and positively correlated with H-Y stage(r = 0.222,P = 0.049).Pearson correlation analysis showed a negative correlation between sLAG3 level and use ratio of dopamine receptor agonist(DA%)(r=-0.227,P = 0.049).? There was no significant association between serum sLAG3 and PD clinical subtypes(r =-0.156,P = 0.169),non-motor symptoms(NMSS,RBD,RLS)or MDS-UPDRS scores(r = 0.149,P = 0.189).4.Multiple linear regression analysis of serum sLAG3 in PD groupThe gender(? = 0.512,P<0.001),H-Y stage(?=0.299,P = 0.002)and DA%(p =-0.257,P = 0.009)were risk factors of serum sLAG3,with the biggest impact on gender,followed by H-Y stage.5.Ordinal multi-class logistic regression analysis of H-Y stageThe disease duration(OR=1.374,P<0.001),LEDD(OR = 1.002,P<0.001)and serum sLAG3(OR = 1.002,P = 0.043)were risk factors correlated with H-Y stage.6.ROC curve analysis of sLAG3 as a possible PD biomarkerFor all PD patients,an optimal cut-off value of 800.001 pg/mL for sLAG3 was identified compared with control group,and the AUC was 0.722(P<0.001),with a sensitivity of 67.39%and specificity of 67.50%.For women,the AUC was 0.823,with a sensitivity of 73.33%and specificity of 82.50%.Compared with women,men showed a lower sensitivity of 72.34%and specificity of 57.50%,and the AUC was 0.640.Conclusion1.Serum sLAG3 level was substantially elevated in PD patients compared with healthy controls and PSP patients.2.Serum sLAG3 level was correlated to gender and H-Y stage in PD patients.3.There was no significant association between serum sLAG3 and clinical subtypes,non-motor symptoms or MDS-UPDRS scores.4.Serum sLAG3 is one of the possible biomarkers for PD diagnosis and a larger sample size is needed for further study.