title: Plasma C3 and C3a levels in cryptogenic and large-vessel disease stroke: associations with outcome.
abstract: OBJECTIVE
  Inflammation seems to be a key player in the pathophysiology of stroke. In this study, we compared plasma C3 and C3a levels in cryptogenic and large-vessel disease (LVD) subtypes of ischemic stroke and control subjects and evaluated their association to outcome at 3 months and 2 years.
  
  
  METHODS
  C3 and C3a levels in plasma of 79 cryptogenic stroke and 73 LVD stroke patients, sampled within 10 days and at 3 months after stroke, and age- and sex-matched control subjects from the Sahlgrenska Academy Study on Ischemic Stroke were measured by ELISA. Functional outcome was assessed with the modified Rankin Scale.
  
  
  RESULTS
  Plasma C3 was increased in both stroke groups at both time points. Systemic elevation of C3a was limited to the acute phase in the cryptogenic stroke group, whereas plasma C3a levels in the LVD group were also elevated at the 3-month follow-up. In the LVD group, plasma C3 levels in the upper third at the 3-month follow-up were associated with an unfavorable outcome after 3 months independently of age and sex: odds ratio (OR) 5.56; 95% confidence interval (CI) 1.03-29.93; p = 0.045; as well as after 2 years: OR 4.75; 95% CI 1.11-20.30; p = 0.036. In the cryptogenic stroke group, high plasma C3a levels in the acute phase were associated with an unfavorable outcome after 3 months: OR 3.75; 95% CI 1.01-13.96; p = 0.049 in univariate analysis but not after adjustment for age and sex (p = 0.050).
  
  
  CONCLUSIONS
  Plasma C3 and C3a levels are elevated in cryptogenic and LVD stroke and the predictive value of these markers may depend on stroke subtype. Further studies on the role of the complement system in ischemic stroke outcome based on larger patient populations and controlling for the effect of infections, are clearly warranted.
authors.affiliation: Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation, The Sahlgrenska Academy at University of Gothenburg, Medicinaregatan 9a, Göteborg, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Stokowska
authors.forename: Sandra
authors.initials: S
authors.lastname: Olsson
authors.forename: Lukas
authors.initials: L
authors.lastname: Holmegaard
authors.forename: Katarina
authors.initials: K
authors.lastname: Jood
authors.forename: Christian
authors.initials: C
authors.lastname: Blomstrand
authors.forename: Christina
authors.initials: C
authors.lastname: Jern
authors.forename: Marcela
authors.initials: M
authors.lastname: Pekna
mesh_terms: D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D003176:Complement C3 / Q000378:metabolism*; D015926:Complement C3a / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012720:Severity of Illness Index; D020521:Stroke / Q000097:blood / Q000145:classification* / Q000175:diagnosis*
chemical_list: D015415:Biomarkers; D003176:Complement C3; D015926:Complement C3a; D002097:C-Reactive Protein