Autoantibody against a protease domain of caspase-8 in patients with systemic sclerosis

Toshifumi Yamaoka, Fumihide Ogawa, Eiji Muroi, Toshihide Hara, Kazuhiro Komura, Yohei Iwata, Motoi Takenaka, Kazuhiro Shimizu, Minoru Hasegawa, Manabu Fujimoto, Shinichi Sato

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Background: Systemic sclerosis (SSc) is characterized by autoantibodies against various cellular components. Objective: To determine the presence or levels of antibodies (Abs) against a protease domain (PD) of caspase-8 and their clinical relevance in SSc. Methods: Anti-caspase-8 PD Ab was examined by enzyme-linked immunosorbent assay and immunoblotting using human recombinant caspase-8 PD. Caspase-8 activity was evaluated by spectrophotometric detection of cleavage from p-nitroanilide-labeled IETD, a substrate of caspase-8. Results: IgG anti-caspase-8 PD Ab levels in patients with SSc, systemic lupus erythematosus, or dermatomyositis were higher than in normal controls (CTL). Furthermore, anti-caspase-8 PD Ab levels in limited cutaneous SSc (lSSc) patients were elevated compared to diffuse cutameous SSc (dSSc) patients. To investigate the clinical correlation, laboratory findings were compared between SSc patients with high levels (>the mean+2SD of CTL) of anti -caspase-8 PD Ab and those with low levels. SSc patients with high levels exhibited lower frequency of male and decreased C-reactive protein levels relative to those with low levels. Immunoblotting showed that anti-caspase-8 PD Ab was present in all SSc patients examined, while it was also detected in 75% of CTL. Caspase-8 activity was inhibited by IgG isolated from sera of SSc patients and CTL, although inhibitory effect was greater in SSc patients than CTL. Conclusion: These results suggest that immune response to caspase-8 occurs in healthy individuals, although it is greater in patients with systemic autoimmune diseases including SSc. Furthermore, high levels of anti-caspase-8 PD Ab may be a serological indicator for a milder SSc subset.

Original languageEnglish
Pages (from-to)998-1004
Number of pages7
JournalClinical and Experimental Rheumatology
Volume26
Issue number6
Publication statusPublished - 11-2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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