Abstract:  Objective:Assessing whether lupus  nephritis  （ LN）  is  active  or  not  is  crucial  for  developing  tailored treatment plans and improving patients＇ prognosis. The objective of this study was to identify novel markers in the circulation of LN patients that can reflect  disease  activity. Methodology:Olink proteomics  was  employed to  detect 92 inflammatory molecules and 92 immune response molecules in the plasma of three cohorts: healthy controls （ CON1， n = 10）， active LN patients （ ALN1， n = 9）  and  inactive  LN  patients  （ ILN1，  n = 9）.  Additionally，  prospective  cohort  was  included  in  the analysis. The molecules identified through screening were subsequently validated using ELISA in a larger sample size of LN patients （ n = 99）  and in a follow⁃up cohort （ n = 50）.    Results:Compared with the CON1 group and the ILN1 group， the ALN1 group  had  17  differential  molecules，  and  the  area  under  the  curve  （ AUC）  distinguishing  ALN1  from  ILN1  was greater than 0.8. A cohort study showed that 11 of these molecules decreased with treatment remission. After screening the 11 molecules， LIFR and BTN3A2 were finally identified as meeting the criteria.  In a larger sample and cohort， these two molecules were validated to be significantly higher in active LN patients than in inactive patients. Both LIFR and BTN3A2 were positively  correlated  with  the  SLE⁃DAI  score，  with  correlation  coefficients  of  0.557  and  0.468，  respectively.  The cohort  results  showed  that  the  levels  of  these  two  molecules  in  circulation  significantly  decreased  with  disease  remission，while no changes were observed in those who did not achieve remission.    Conclusion:In this study， wecirculating LIFR and BTN3A2 serve as novel biomarkers that mirror LN isease activity.

Key words: lupus nephritis, disease activity, biomarker