title: Antibodies recognising sulfated carbohydrates are prevalent in systemic sclerosis and associated with pulmonary vascular disease.
abstract: BACKGROUND
  Glycosylation represents an important modification that regulates biological processes in tissues relevant for disease pathogenesis in systemic sclerosis (SSc), including the endothelium and extracellular matrix. Whether patients with SSc develop antibodies to carbohydrates is not known.
  
  
  OBJECTIVE
  To determine the prevalence and clinical phenotype associated with serum IgG antibodies recognising distinct glycans in patients with SSc.
  
  
  METHODS
  Pooled serum samples from patients with SSc and controls were screened for the presence of specific anticarbohydrate antibodies using a novel array containing over 300 glycans. Antibody titres to 4-sulfated N-acetyl-lactosamine (4S-LacNAc, (4OSO3)Galβ1-4GlcNAc) were determined in 181 individual serum samples from patients with SSc by ELISA and associated with disease phenotype.
  
  
  RESULTS
  4S-LacNAc was identified as a target in pooled SSc serum. Anti-4S-LAcNAc antibodies were detected in 27/181 patients with SSc (14.9%) compared with 1/40 healthy controls (2.5%). Sulfation at position C4 of galactose (4S-LacNAc) was found to be critical for immunogenicity. Anti-4S-LacNAc antibody-positive patients with SSc had a higher prevalence of pulmonary hypertension by echocardiography than anti-4S-LacNAc-negative patients (15/27 (55.7%) vs 49/154 (31.8%), p=0.02) with an OR of 2.6 (95% CI 1.1 to 6.3). Anti-4S-LacNAc-positive patients accounted for 23.4% of all patients with pulmonary hypertension.
  
  
  CONCLUSIONS
  Serum from patients with SSc contains IgG antibodies targeting distinct sulfated carbohydrates. The presence of anti-4S-LacNAc antibodies is associated with a high prevalence of pulmonary hypertension. These results suggest that specific post-translational carbohydrate modifications may act as important immunogens in SSc and may contribute to disease pathogenesis.
authors.affiliation: Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. tgrader1@jhmi.edu
authors.forename: Thomas
authors.initials: T
authors.lastname: Grader-Beck
authors.forename: Francesco
authors.initials: F
authors.lastname: Boin
authors.forename: Stephan
authors.initials: S
authors.lastname: von Gunten
authors.forename: David
authors.initials: D
authors.lastname: Smith
authors.forename: Antony
authors.initials: A
authors.lastname: Rosen
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Bochner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000606:Amino Sugars / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D005690:Galactose / Q000276:immunology; D006031:Glycosylation; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D011134:Polysaccharides / Q000737:chemistry / Q000276:immunology*; D012595:Scleroderma, Systemic / Q000150:complications / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000276:immunology; D055815:Young Adult
chemical_list: C569197:4-sulfated N-acetyl-lactosamine; D000606:Amino Sugars; D001323:Autoantibodies; D007074:Immunoglobulin G; D011134:Polysaccharides; D005690:Galactose