title: Plasma complement and vascular complement deposition in patients with coronary artery disease with and without inflammatory rheumatic diseases.
abstract: OBJECTIVE
  Inflammatory rheumatic diseases (IRD) are associated with accelerated coronary artery disease (CAD), which may result from both systemic and vascular wall inflammation. There are indications that complement may be involved in the pathogenesis of CAD in Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA). This study aimed to evaluate the associations between circulating complement and complement activation products with mononuclear cell infiltrates (MCI, surrogate marker of vascular inflammation) in the aortic media and adventitia in IRDCAD and non-IRDCAD patients undergoing coronary artery bypass grafting (CABG). Furthermore, we compared complement activation product deposition patterns in rare aorta adventitial and medial biopsies from SLE, RA and non-IRD patients.
  
  
  METHODS
  We examined plasma C3 (p-C3) and terminal complement complexes (p-TCC) in 28 IRDCAD (SLE = 3; RA = 25), 52 non-IRDCAD patients, and 32 IRDNo CAD (RA = 32) from the Feiring Heart Biopsy Study. Aortic biopsies taken from the CAD only patients during CABG were previously evaluated for adventitial MCIs. The rare aortic biopsies from 3 SLE, 3 RA and 3 non-IRDCAD were assessed for the presence of C3 and C3d using immunohistochemistry.
  
  
  RESULTS
  IRDCAD patients had higher p-TCC than non-IRDCAD or IRDNo CAD patients (p<0.0001), but a similar p-C3 level (p = 0.42). Circulating C3 was associated with IRD duration (ρ, p-value: 0.46, 0.03). In multiple logistic regression analysis, IRD remained significantly related to the presence and size of MCI (p<0.05). C3 was present in all tissue samples. C3d was detected in the media of all patients and only in the adventitia of IRD patients (diffuse in all SLE and focal in one RA).
  
  
  CONCLUSIONS
  The independent association of IRD status with MCI and the observed C3d deposition supports the unique relationship between rheumatic disease, and, in particular, SLE with the complement system. Exaggerated systemic and vascular complement activation may accelerate CVD, serve as a CVD biomarker, and represent a target for new therapies.
authors.affiliation: Lupus Center of Excellence, Autoimmunity Institute, Department of Medicine, Allegheny Health Network, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Kelly J
authors.identifier: http://orcid.org/0000-0002-5699-7773
authors.initials: KJ
authors.lastname: Shields
authors.affiliation: Department of Immunology, Oslo University Hospital, and K.G. Jebsen IRC, University of Oslo, Oslo, Norway.|Research Laboratory, Nordland Hospital, Bodø, and Faculty of Health Sciences, K.G. Jebsen TREC, University of Tromsø, Tromsø, Norway.|Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Tom Eirik
authors.initials: TE
authors.lastname: Mollnes
authors.affiliation: Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
authors.forename: Jon Roger
authors.initials: JR
authors.lastname: Eidet
authors.affiliation: Department of Rheumatology, Lillehammer Hospital for Rheumatic Diseases, Lillehammer, Norway.
authors.forename: Knut
authors.initials: K
authors.lastname: Mikkelsen
authors.affiliation: Department of Cardiothoracic and Vascular Surgery, University Hospital of North Norway, Tromsø, Norway.
authors.forename: Sven M
authors.initials: SM
authors.lastname: Almdahl
authors.affiliation: Humanitas Clinical and Research Center, Rozzano, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bottazzi
authors.affiliation: Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
authors.forename: Torstein
authors.initials: T
authors.lastname: Lyberg
authors.affiliation: Lupus Center of Excellence, Autoimmunity Institute, Department of Medicine, Allegheny Health Network, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Susan
authors.initials: S
authors.lastname: Manzi
authors.affiliation: Lupus Center of Excellence, Autoimmunity Institute, Department of Medicine, Allegheny Health Network, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Ahearn
authors.affiliation: Department of Rheumatology, Lillehammer Hospital for Rheumatic Diseases, Lillehammer, Norway.|Research Department, Innlandet Hospital Trust, Brumunddal, Norway.|Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.|School of Medicine, Harvard University, Boston, Massachusetts, United States of America.
authors.forename: Ivana
authors.initials: I
authors.lastname: Hollan
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D003176:Complement C3 / Q000378:metabolism; D015933:Complement C3d / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000097:blood*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007249:Inflammation / Q000097:blood*; D008180:Lupus Erythematosus, Systemic / Q000097:blood; D008297:Male; D008875:Middle Aged; D012216:Rheumatic Diseases / Q000097:blood*; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D003176:Complement C3; D015933:Complement C3d; D003165:Complement System Proteins