Antibodies recognising sulfated carbohydrates are prevalent in systemic sclerosis and associated with pulmonary vascular disease

Thomas Grader Beck, Francesco Boin, Stephan Von Gunten, David Smith, Antony Rosen, Bruce S. Bochner

Research output: Contribution to journalArticle

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)Galaβ1-4GlcNAc) 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.

Original languageEnglish (US)
Pages (from-to)2218-2224
Number of pages7
JournalAnnals of the Rheumatic Diseases
Volume70
Issue number12
DOIs
StatePublished - Dec 2011

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Systemic Scleroderma
Vascular Diseases
Lung Diseases
Carbohydrates
Antibodies
Pulmonary Hypertension
Serum
Polysaccharides
Immunoglobulin G
Glycosylation
Echocardiography
4-sulfated N-acetyl-lactosamine
Phenotype
Biological Phenomena
Galactose
Post Translational Protein Processing
Endothelium
Extracellular Matrix
Tissue
Enzyme-Linked Immunosorbent Assay

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Allergy

Cite this

Antibodies recognising sulfated carbohydrates are prevalent in systemic sclerosis and associated with pulmonary vascular disease. / Grader Beck, Thomas; Boin, Francesco; Von Gunten, Stephan; Smith, David; Rosen, Antony; Bochner, Bruce S.

In: Annals of the Rheumatic Diseases, Vol. 70, No. 12, 12.2011, p. 2218-2224.

Research output: Contribution to journalArticle

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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)Galaβ1-4GlcNAc) 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.",
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AU - Boin, Francesco

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AU - Rosen, Antony

AU - Bochner, Bruce S.

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