title: Natural autoantibodies reactive with glycosaminoglycans in rheumatoid arthritis.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  The highly abundant and cross-reactive, GAG-specific natural autoantibodies in serum may serve as novel disease-state markers in patients with rheumatoid arthritis.
authors.affiliation: Department of Genetics, Cell- and Immunobiology, Semmelweis University, Nagyvarad ter 4, H-1089, Budapest, Hungary. bonobo97@gmail.com
authors.forename: Bence
authors.initials: B
authors.lastname: György
authors.forename: László
authors.initials: L
authors.lastname: Tóthfalusi
authors.forename: György
authors.initials: G
authors.lastname: Nagy
authors.forename: Mária
authors.initials: M
authors.lastname: Pásztói
authors.forename: Pál
authors.initials: P
authors.lastname: Géher
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Lörinc
authors.forename: Anna
authors.initials: A
authors.lastname: Polgár
authors.forename: Bernadett
authors.initials: B
authors.lastname: Rojkovich
authors.forename: Ilona
authors.initials: I
authors.lastname: Ujfalussy
authors.forename: Gyula
authors.initials: G
authors.lastname: Poór
authors.forename: Péter
authors.initials: P
authors.lastname: Pócza
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Wiener
authors.forename: Petra
authors.initials: P
authors.lastname: Misják
authors.forename: Agnes
authors.initials: A
authors.lastname: Koncz
authors.forename: András
authors.initials: A
authors.lastname: Falus
authors.forename: Edit I
authors.initials: EI
authors.lastname: Buzás
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006025:Glycosaminoglycans / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012217:Rheumatoid Factor / Q000097:blood; D013582:Synovial Fluid / Q000276:immunology
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D006025:Glycosaminoglycans; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D002097:C-Reactive Protein; D012217:Rheumatoid Factor
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