title: Autoantibody against a protease domain of caspase-8 in patients with systemic sclerosis.
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, anit-caspase-8 PD Ab levels in limited cutaneous SSc (ISSc) 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 level exhibited lower frequency of male and decreased C-reactive protein levels relative to those with low levels. Immunoblotting showed the anit-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.
  
  
  CONCLUSIONS
  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 level of anti-caspase-8 PD Ab may be a serological indicator for a milder SSc subset.
authors.affiliation: Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yamaoka
authors.forename: F
authors.initials: F
authors.lastname: Ogawa
authors.forename: E
authors.initials: E
authors.lastname: Muroi
authors.forename: T
authors.initials: T
authors.lastname: Hara
authors.forename: K
authors.initials: K
authors.lastname: Komura
authors.forename: Y
authors.initials: Y
authors.lastname: Iwata
authors.forename: M
authors.initials: M
authors.lastname: Takenaka
authors.forename: K
authors.initials: K
authors.lastname: Shimizu
authors.forename: M
authors.initials: M
authors.lastname: Hasegawa
authors.forename: M
authors.initials: M
authors.lastname: Fujimoto
authors.forename: S
authors.initials: S
authors.lastname: Sato
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D015551:Autoimmunity; D053181:Caspase 8 / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D004789:Enzyme Activation / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D008875:Middle Aged; D017434:Protein Structure, Tertiary; D012595:Scleroderma, Systemic / Q000276:immunology* / Q000378:metabolism; D012720:Severity of Illness Index
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C505530:CASP8 protein, human; D053181:Caspase 8