Protoarray analysis reveals novel autoantigens targeted by autoantibodies associated with DNA-repair pathway in systemic erythematosus lupus (HUM2P.330)

Systemic erythematosus lupus (SLE) is an autoimmune disease characterized by presence of autoantibodies (autoAbs) against a broad spectrum of self-antigens. In order to identify novel autoAbs associated with SLE, we utilized a Protoarray bearing 9,500 antigens to screen IgG and IgM autoAbs in sera of SLE patients. 446 IgG and 1218 IgM autoAbs were identified to be significantly elevated in SLE patients compared with healthy controls (p<0.05). Protoarray revealed not only the previously described autoAbs such as antibodies against dsDNA, SSA/SSB, Histone and Sm/RNP, but also uncovered autoAbs against a broad range of novel antigens including 151 nuclear-associated antigens and 150 cytoplasma or membrane-associated antigens. The Protoarray results were further validated by ELISA in a larger cohort of SLE patients and controls. Besides, 65 of the IgG autoAb-targeted proteins were also disregulated in SLE on mRNA level by microarray analysis. Pathway analysis recognized significant enrichment of antigens involved in cell proliferation and DNA repair pathways which were targeted by IgG autoAbs including APEX1, AURKA, CSNK1G1, EIF2C1, HMGB1, IFIT5, MAPKAPK3, PADI4, PRKRA, RALGPS1, UBE2S and VRK1. The elevated IgG autoAbs to APEX1 and other proteins in the pathway may reflect the compromised DNA-repair activity during DNA replication in SLE. In conclusion, identification of novel autoAbs by protoarray may shed light on some of the pathogenic pathways leading to disease in SLE.