Open Access Research article

Natural autoantibodies reactive with glycosaminoglycans in rheumatoid arthritis

Bence György1, László Tóthfalusi2, György Nagy13, Mária Pásztói1, Pál Géher3, Zsolt Lörinc4, Anna Polgár5, Bernadett Rojkovich3, Ilona Ujfalussy3, Gyula Poór5, Péter Pócza1, Zoltán Wiener1, Petra Misják1, Agnes Koncz6, András Falus17 and Edit I Buzás1*

Author Affiliations

1 Department of Genetics, Cell- and Immunobiology, Semmelweis University, Nagyvarad ter 4, H-1089, Budapest, Hungary

2 Department of Pharmacodynamics, Semmelweis University, Nagyvarad ter 4, H-1089, Budapest, Hungary

3 Department of Rheumatology, Semmelweis University, Frankel Leó utca 54, H-1027, Budapest, Hungary

4 Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, Karolina út 29, H-1518, Budapest, Hungary

5 National Institute of Rheumatology and Physiotherapy, Frankel Leó utca 25-29, H-1023, Budapest, Hungary

6 Heim Pal Hospital, Ülloi út 86, H-1089, Budapest, Hungary

7 Research Group for Inflammation Biology and Immunogenomics, Hungarian Academy of Sciences, Nagyvarad ter 4, H-1089, Budapest, Hungary

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Arthritis Research & Therapy 2008, 10:R110  doi:10.1186/ar2507

Published: 12 September 2008

Abstract

Introduction

Although natural autoantibodies make up the majority of circulating immunoglobulins and are also present in high numbers in therapeutically used intravenous immunoglobulin preparations, they have received little attention and their precise role remains largely unknown. An increasing awareness of the importance of posttranslational autoantigen modifications and glycobiology led us to explore carbohydrate-reactive natural autoantibodies in patients with rheumatoid arthritis. This study examined systematic antibodies reactive to glycosaminoglycans (GAGs), the carbohydrate components of proteoglycans that are released in large amounts from degrading cartilage.

Methods

To measure antibodies reactive to six different types of GAGs, a specialised ELISA was used in which the carbohydrates were covalently linked to the plastic surface through a 2 nm spacer. Sera from rheumatoid arthritis patients (n = 66), umbilical cord serum samples (n = 11) and adult controls (n = 54) were studied. In order to explore cross-reactivity with microbial antigens, bacterial peptidoglycans and fungal polysaccharides were used. Sera and synovial fluid samples were also tested using a GlycoChip carbohydrate array to characterise individual carbohydrate recognition patterns. We followed a multistep statistical screening strategy for screening GAG-reactive antibodies as predictive disease markers.

Results

While anti-GAG antibodies were absent in the umbilical cord sera, they were readily detectable in adult controls and were significantly elevated in patients with rheumatoid arthritis (p < 0.001). Anti-GAG antibodies showed significant cross-reactivity among different types of GAGs. They also reacted with bacterial peptidoglycans and fungal polysaccharides. Interestingly, anti-chondroitin sulphate C IgM antibody levels showed inverse correlation both with the Disease Activity Score (DAS) 28 scores and C-reactive protein (CRP) levels in rheumatoid arthritis.

Conclusion

The highly abundant and cross-reactive, GAG-specific natural autoantibodies in serum may serve as novel disease-state markers in patients with rheumatoid arthritis.