Article Text

other Versions

PDF
Extended report
Antibodies recognising sulfated carbohydrates are prevalent in systemic sclerosis and associated with pulmonary vascular disease
  1. Thomas Grader-Beck1,
  2. Francesco Boin1,
  3. Stephan von Gunten2,3,
  4. David Smith4,
  5. Antony Rosen1,
  6. Bruce S Bochner2
  1. 1Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  2. 2Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  3. 3Institute of Pharmacology, University of Bern, Bern, Switzerland
  4. 4Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA
  1. Correspondence to Thomas Grader-Beck, Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine, 5200 Eastern Avenue, Suite 4100, Mason Lord Center Tower, Baltimore, MD 21224, USA; tgrader1{at}jhmi.edu

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.

Objectives 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.

Conclusion 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.

Statistics from Altmetric.com

Footnotes

  • Funding DS's work, including glycan array analyses, was supported by the NIH (grant GM-62116). FB was supported by the Scleroderma Research Foundation and the NIH (grant AR-055667). TG-B was supported by the NIH (grants AI-071072 and AR-053503).

  • Ethics approval This study was conducted with the approval of the Johns Hopkins Institutional Review Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.