Serum alpha-1-antitrypsin level in the severity prognosis of systemic lupus erythematosus patients: Systematic exploration of novel biomarker.

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affecting multi-organs injury and failure. The rapid, precision, and specificity prognosis by laboratory investigations could prevent active stage and severity in the disease. Aims: To systematically explore and investigate the candidate serum protein for development into the novel biomarker for severity prognosis of SLE patients. Methods: The proteins previously reported in abnormal level in serum/plasma of SLE patients since 2014-2020 were comprehensive collected. Thereafter, these serum proteins that found in other diseases were excluded. The association with molecules related to SLE severity of these candidate proteins were then predicted using bioinformatics STIRNG tool. The level of altered protein, which had the strong interaction to the severity molecules in serumof SLE patients was validated by Western blot, analyzed the correlation with anti-nuclear antigen (ANA) and performance of diagnosis, respectively. Results: From 26 collected serum/plasma proteins, alpha-1-antitrypsin protein was found the abnormal level in only SLE patients and strongly associated with severity molecules including C-reactive protein (CRP), complement C3, and C4. Additionally, the validation of serum alpha-1-antitrypsin in SLE patients exhibited the higher level than healthy controls and also had the positive correlation with ANA titer (r = 0.710). Furthermore, the area under ROC curve for diagnostic power of alpha-1-antitrypsin was 0.970 with 100% sensitivity and 90% specificity at cut-off 0.131/total serum protein. Conclusions: The higher level of alpha-1-antitrypsin in serum samples of SLE patients indicated as the novel biomarker for reliable and specific prognosis of disease severity.