title: Anti-ApoA-1 IgG serum levels predict worse poststroke outcomes.
abstract: BACKGROUND
  Autoantibodies to apolipoprotein A-1 (anti-ApoA-1 IgG) were shown to predict major adverse cardiovascular events and promote atherogenesis. However, their potential relationship with clinical disability and ischaemic lesion volume after acute ischaemic stroke (AIS) remains unexplored.
  
  
  METHODS
  We included n = 76 patients admitted for AIS and we investigated whether baseline serum anti-ApoA-1 IgG levels could predict (i) AIS-induced clinical disability [assessed by the modified Rankin Scale (mRS)], and (ii) AIS-related ischaemic lesion volume [assessed by Computed Tomography (CT)]. We also evaluated the possible pro-apoptotic and pro-necrotic effects of anti-ApoA-1 IgG on human astrocytoma cell line (U251) using flow cytometry.
  
  
  RESULTS
  High levels of anti-ApoA-1 IgG were retrieved in 15·8% (12/76) of patients. Increased baseline levels of anti-ApoA-1 IgG were independently correlated with worse mRS [β = 0·364; P = 0·002; adjusted odds ratio (OR): 1·05 (95% CI 1·01-1·09); P = 0·017] and CT-assessed ischaemic lesion volume [β = 0·333; P < 0·001; adjusted OR: 1·06 (95% CI 1·01-1·12); P = 0·048] at 3 months. No difference in baseline clinical, biochemical and radiological characteristics was observed between patients with high vs. low levels of anti-ApoA-1 IgG. Incubating human astrocytoma cells with anti-ApoA-1 IgG dose dependently induced necrosis and apoptosis of U251 cells in vitro.
  
  
  CONCLUSIONS
  Anti-ApoA-1 IgG serum levels at AIS onset are associated with poorer clinical recovery and worse brain lesion volume 3 months after AIS. These observations could be partly explained by the deleterious effect of anti-ApoA-1 IgG on human brain cell survival in vitro and may have clinical implication in the prediction of poor outcome in AIS.
authors.affiliation: First Clinic of Internal Medicine, Department of Internal Medicine, School of Medicine, University of Genoa, Genoa, Italy.
authors.forename: Federico
authors.identifier: http://orcid.org/0000-0003-2957-4078
authors.initials: F
authors.lastname: Carbone
authors.affiliation: Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Satta
authors.affiliation: First Clinic of Internal Medicine, Department of Internal Medicine, School of Medicine, University of Genoa, Genoa, Italy.|IRCCS AOU San Martino - IST, Genoa, Italy.|Centre of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Montecucco
authors.affiliation: Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Julien
authors.initials: J
authors.lastname: Virzi
authors.affiliation: Division of Cardiology, Department of Medical Specialties, Foundation for Medical Researches, University of Geneva, Geneva, Switzerland.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Burger
authors.affiliation: Division of Cardiology, Department of Medical Specialties, Foundation for Medical Researches, University of Geneva, Geneva, Switzerland.
authors.forename: Aline
authors.initials: A
authors.lastname: Roth
authors.affiliation: Department of Biological, Psychiatric and Psychological Science, Azienda Ospedaliera-Universitaria, Arcispedale S. Anna, Ferrara, Italy.
authors.forename: Gloria
authors.initials: G
authors.lastname: Roversi
authors.affiliation: Department of Biological, Psychiatric and Psychological Science, Azienda Ospedaliera-Universitaria, Arcispedale S. Anna, Ferrara, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Tamborino
authors.affiliation: Department of Biological, Psychiatric and Psychological Science, Azienda Ospedaliera-Universitaria, Arcispedale S. Anna, Ferrara, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Casetta
authors.affiliation: Institute for Maternal and Child Health 'IRCCS Burlo Garofolo', Trieste, Italy.
authors.forename: Silva
authors.initials: S
authors.lastname: Seraceni
authors.affiliation: Section of Medical Biochemistry, Molecular Biology and Genetics, Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Trentini
authors.affiliation: Section of Medical Biochemistry, Molecular Biology and Genetics, Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Padroni
authors.affiliation: First Clinic of Internal Medicine, Department of Internal Medicine, School of Medicine, University of Genoa, Genoa, Italy.|IRCCS AOU San Martino - IST, Genoa, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Dallegri
authors.affiliation: Division of Neurology, Department of Clinical Neurosciences, Geneva University Hospital, Geneva, Switzerland.
authors.forename: Patrice H
authors.initials: PH
authors.lastname: Lalive
authors.affiliation: Division of Cardiology, Department of Medical Specialties, Foundation for Medical Researches, University of Geneva, Geneva, Switzerland.
authors.forename: François
authors.initials: F
authors.lastname: Mach
authors.affiliation: Neuroradiology Unit, Department of Neurosciences and Rehabilitation, Azienda Ospedaliera-Universitaria, Arcispedale S. Anna, Ferrara, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Fainardi
authors.affiliation: Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vuilleumier
mesh_terms: D000368:Aged; D016632:Apolipoprotein A-I / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001323:Autoantibodies / Q000276:immunology* / Q000494:pharmacology; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D005904:Glial Fibrillary Acidic Protein / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D066298:In Vitro Techniques; D018950:Lipopolysaccharide Receptors / Q000187:drug effects / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009336:Necrosis; D016017:Odds Ratio; D010865:Pilot Projects; D011379:Prognosis; D011446:Prospective Studies; D020127:Recovery of Function; D012720:Severity of Illness Index; D020521:Stroke / Q000000981:diagnostic imaging / Q000276:immunology* / Q000503:physiopathology; D051195:Toll-Like Receptor 2 / Q000187:drug effects / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000187:drug effects / Q000378:metabolism; D014057:Tomography, X-Ray Computed
chemical_list: D016632:Apolipoprotein A-I; D001323:Autoantibodies; D005904:Glial Fibrillary Acidic Protein; D007074:Immunoglobulin G; D018950:Lipopolysaccharide Receptors; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4
keywords: Acute ischaemic stroke; anti-ApoA-1 IgG; computed tomography; modified Rankin Scale