title: Antibodies against carbamylated proteins and cyclic citrullinated peptides in systemic lupus erythematosus: results from two well-defined European cohorts.
abstract: Articular manifestations are common in systemic lupus erythematosus (SLE) whereas erosive disease is not. Antibodies to cyclic citrullinated peptide (anti-CCP) are citrulline-dependent in rheumatoid arthritis (RA), whereas the opposite is suggested in SLE, as reactivity with cyclic arginine peptide (CAP) is typically present. Antibodies targeting carbamylated proteins (anti-CarP) may occur in anti-CCP/rheumatoid factor (RF)-negative cases long before clinical onset of RA. We analysed these antibody specificities in sera from European patients with SLE in relation to phenotypes, smoking habits and imaging data.
  
  
  
  Cases of SLE (n = 441) from Linköping, Sweden, and Leiden, the Netherlands, were classified according to American College of Rheumatology (ACR) and/or Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) criteria. IgG anti-CCP, anti-CAP and anti-CarP were analysed by immunoassays. Radiographic data from 102 Swedish patients were available.
  
  
  
  There were 16 Linköping (6.8%) and 11 Leiden patients (5.4%) who were anti-CCP-positive, of whom approximately one third were citrulline-dependent: 40/441 (9.1%) were anti-CarP-positive, and 33% of the anti-CarP-positive patients were identified as anti-CCP-positive. No associations were found comparing anti-CCP or anti-CarP with ACR-defined phenotypes, immunologic abnormalities or smoking habits. Radiographically confirmed erosions were found in 10 patients, and were significantly associated with anti-CCP, anti-CarP and RF. Musculoskeletal ultrasonography scores were higher in anti-CCP-positive compared to anti-CCP-negative patients.
  
  
  
  In the hitherto largest anti-CarP study in SLE, we demonstrate that anti-CarP is more prevalent than anti-CCP and that the overlap is limited. We obtained some evidence that both autoantibodies seem to be associated with erosivity. Similar pathogenetic mechanisms to those seen in RA may be relevant in a subgroup of SLE cases with a phenotype dominated by arthritis.
authors.affiliation: Rheumatology/AIR, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Ziegelasch
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, C1-R, LUMC, PO Box 9600, Leiden, 2300, RC, The Netherlands.
authors.forename: Myrthe A M
authors.initials: MA
authors.lastname: van Delft
authors.affiliation: Rheumatology/AIR, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Philip
authors.initials: P
authors.lastname: Wallin
authors.affiliation: Rheumatology/AIR, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Skogh
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, C1-R, LUMC, PO Box 9600, Leiden, 2300, RC, The Netherlands.
authors.forename: César
authors.initials: C
authors.lastname: Magro-Checa
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, C1-R, LUMC, PO Box 9600, Leiden, 2300, RC, The Netherlands.
authors.forename: Gerda M
authors.initials: GM
authors.lastname: Steup-Beekman
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, C1-R, LUMC, PO Box 9600, Leiden, 2300, RC, The Netherlands.
authors.forename: Leendert A
authors.initials: LA
authors.lastname: Trouw
authors.affiliation: Rheumatology/AIR, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Alf
authors.initials: A
authors.lastname: Kastbom
authors.affiliation: Rheumatology/AIR, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. christopher.sjowall@liu.se.|Rheumatology Unit, University Hospital, Linköping, SE-581 85, Sweden. christopher.sjowall@liu.se.
authors.forename: Christopher
authors.identifier: 0000-0003-0900-2048
authors.initials: C
authors.lastname: Sjöwall
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D015331:Cohort Studies; D005060:Europe; D005260:Female; D006801:Humans; D007118:Immunoassay; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D011506:Proteins; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D010456:Peptides, Cyclic; D011506:Proteins; C487763:cyclic citrullinated peptide
keywords: Anti-CCP; Anti-CarP; Rheumatoid arthritis; Rheumatoid factor; Systemic lupus erythematosus; Ultrasonography