Background and aims Autoantibodies to Sm, dsDNA, Nucleosome (Nuc) and Ribosome P protein (Rib-P) are highly specific to Systemic Lupus Erythematosis (SLE) diagnosis. We aimed to compare Chemiluminescent immunoassay (CLIA) platform (BioCLIA 1200) and Line ImmunoAssay (LIA) on the conformational detection of these SLE specific antibodies through a randomised, independent and multi-centre clinical study in China. Methods A total of 717 samples suffered from systemic autoimmune diseases (SLE, n=535; SjS, n=99; SSc, n=35; RA, n=48) and healthy individuals (n=94) from 6 Tier-3 hospitals from China were tested with BioCLIA 1200 (HOB Biotech Group, Suzhou, PRC) and LIA (EUROIMMUN, Luebeck, Germany). Data were used to evaluate the test agreement between these two conformational assays. Discrepant samples were also retested by ELISA (EUROIMMUN, Luebeck, Germany) and analysed with different diseases panel. Results The overall qualitative agreements between CLIA and LIA were 91.9% (confidence interval, 95% CI 90.0%–93.7%) for anti-Sm, 86.7% (95% CI 84.3%–89.0%) for anti-dsDNA, 89.1% (95% CI 87.0%–91.3%) for anti-Nuc, 89.3% (95% CI 87.7%–91.9%) for anti-Rib-P. The discrepant samples confirmed by ELISA test showed CLIA test data had a better correlation with ELISA. Conclusions The BioCLIA 1200 (a Chemiluminescent immunoassay platform) showed good clinical performance in a large multi-centre clinical study for the detection of SLE specific autoantibodies to Sm, dsDNA, Nuc and Rib-P when comparing with LIA test method. With the additional benefit of full automation, random access and quantitative measurement, BioCLIA 1200 is an alternative to the traditional LIA test for the conformational test of SLE specific antibodies.