Novel Autoantibodies Related to Cell Death and DNA Repair Pathways in Systemic Lupus Erythematosus

Systemic lupus erythematosus(SLE) is a complex autoimmune syndrome characterized by various co-existing autoantibodies(auto Abs) in patients’ blood.However,the full spectrum of auto Abs in SLE has not been comprehensively elucidated.In this study,a commercial platform bearing 9400 antigens(Proto Array) was used to identify auto Abs that were significantly elevated in the sera of SLE patients.By comparing the auto Ab profiles of SLE patients with those of healthy controls,we identified 437 Ig G and 1213 Ig M auto Abs that the expression levels were significantly increased in SLE(P < 0.05).Use of the Proto Array platform uncovered over 300 novel auto Abs targeting a broad range of nuclear,cytoplasmic,and membrane antigens.Molecular interaction network analysis revealed that the antigens targeted by the auto Abs were most significantly enriched in cell death,cell cycle,and DNA repair pathways.A group of auto Abs associated with cell apoptosis and DNA repair function,including those targeting APEX1,AURKA,POLB,AGO1,HMGB1,IFIT5,MAPKAPK3,PADI4,RGS3,SRP19,UBE2 S,and VRK1,were further validated by ELISA and Western blot in a larger cohort.In addition,the levels of auto Abs against APEX1,HMGB1,VRK1,AURKA,PADI4,and SRP19 were positively correlated with the level of anti-ds DNA in SLE patients.Comprehensive auto Ab screening has identified novel auto Abs,which may shed light on potential pathogenic pathways leading to lupus.