Natural autoantibodies reactive with glycosaminoglycans in rheumatoid arthritis.
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.
György
Bence
B
Department of Genetics, Cell- and Immunobiology, Semmelweis University, Nagyvarad ter 4, H-1089, Budapest, Hungary. bonobo97@gmail.com
Tóthfalusi
László
L
Nagy
György
G
Pásztói
Mária
M
Géher
Pál
P
Lörinc
Zsolt
Z
Polgár
Anna
A
Rojkovich
Bernadett
B
Ujfalussy
Ilona
I
Poór
Gyula
G
Pócza
Péter
P
Wiener
Zoltán
Z
Misják
Petra
P
Koncz
Agnes
A
Falus
András
A
Buzás
Edit I
EI
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
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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