Journal des biomarqueurs moléculaires et du diagnostic

Identification of Cerebral Infarction-Specific Antibody Markers from Autoantibodies Detected in Patients with Systemic Lupus Erythematosus

Abstract

Ken-ichiro Goto, Takao Sugiyama, Ryutaro Matsumura, Xiao-Meng Zhang, Risa Kimura, Akiko Taira, Emiko Arita, Katsuro Iwase, Eiichi Kobayashi, Yasuo Iwadate, Naokatsu Saeki, Masahiro Mori, Akiyuki Uzawa, Mayumi Muto, Satoshi Kuwabara, Minoru Takemoto, Kazuki Kobayashi, Harukiyo Kawamura, Ryoichi Ishibashi, Ken-ichi Sakurai, Masaki Fujimoto, Koutaro Yok

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease which may be caused by development of the autoantibodies. On the other hand, SLE is a high-risk group of atherosclerosis, so it is possible that some of autoantibodies in SLE are the result of atherosclerosis-related diseases such as cerebral infarction (CI), cardiovascular disease (CVD) and diabetes mellitus (DM).

Methods: The initial screening of autoantibodies was performed using the protein array method. AlphaLISA was used to analyze the serum antibody levels using synthetic polypeptides as antigens.

Results: After the initial screening using protein array, we identified 67 antigens that were recognized by IgG antibodies in sera of patients with SLE. In the second screening, 170 peptides derived from amino acid sequences of 67 antigens were synthesized and used as antigens for analysis of serum antibody levels by AlphaLISA. The antibody levels for ten peptides were significantly higher in the sera of patients with SLE than in those of healthy donors. Further AlphaLISA analysis of sera of patients with CI, CVD or DM revealed that the serum antibody levels for four peptides derived from SOSTDC1, CTNND1, CLDND1 and CCNG2 were elevated in patients as compared to those of healthy donors.

Conclusions: Serum antibody levels against peptide antigens of SOSTDC1, CTNND1, CLDND1 and CCNG2 are useful markers for diagnosis of the progression of CI, CVD and/or DM.