Systemic lupus erythematosus (SLE) is a systemic autoimmune disease affecting many organs. Many autoantibodies have been associated with the disease, but either in low specificity or low sensitivity of detection. In an aim to screen for better autoantibodies, we profiled the autoantibody repertoire in sera from 30 SLE patients versus 30 healthy controls using a protein microarray containing 5011 non-redundant human proteins, and identified four candidates. We then selected CLIC2 for further verification by ELISA in an extended cohort including 110 SLE, 121 non-AD, 118 RA, 117 SSc, and 105 pSS patients. The positive rate of anti-CLIC2 was 28.18% in SLE patients, significantly higher than those in non-AD, RA, and SSc patients. The presence of anti-CLIC2 in SLE had positive correlation with disease activity in terms of SLEDAI score and several indexes (p < 0.05). (C) 2012 Elsevier Inc. All rights reserved.