Increased concentration of two different advanced glycation end-products detected by enzyme immunoassays with new monoclonal antibodies in sera of patients with rheumatoid arthritis.
BACKGROUND
Levels of pentosidine (representative of advanced glycation end-products) in sera of patients with rheumatoid arthritis are increased when compared with sera of other diagnoses or healthy controls. These levels have been reported to correlate with clinical indices of rheumatoid arthritis activity and with laboratory markers of inflammation. The purpose of this study was to find out if these findings pertain to other advanced glycation end-products.


METHODS
We have developed two immunoassays based on new monoclonal antibodies to advanced glycation end-products. Antibody 103-E3 reacts with an unidentified antigen, formed in the reaction of proteins with ribose, while antibody 8-C1 responds to Nepsilon-(carboxyethyl)lysine. We have used these monoclonal antibodies to measure levels of advanced glycation end-products in sera of patients with rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, and healthy controls. We calculated the correlations between advanced glycation end-product levels in rheumatoid arthritis sera and the Disease Activity Score 28 (DAS28), age, disease duration, CRP, anti-CCP, rheumatoid factor and treatment with corticosteroids, respectively.


RESULTS
Levels of both glycation products were significantly higher in sera of patients with rheumatoid arthritis when compared with sera of patients with systemic lupus erythematosus, osteoarthritis, or the healthy controls. Neither the level of Nepsilon-(carboxyethyl)lysine nor the level of the 103-E3 antigen in rheumatoid arthritis sera correlated with the DAS28-scored rheumatoid arthritis activity. The levels of both antigens in rheumatoid arthritis sera did not correlate with age, gender, corticosteroid treatment, or levels of CRP, anti-CCP antibodies, and rheumatoid factor in sera.


CONCLUSIONS
We report highly specific increases in the levels of two advanced glycation end-products in sera of patients with rheumatoid arthritis. This increase could be explained neither by rheumatoid arthritis activity nor by inflammation. We propose a working hypothesis that presumes the existence of a link between advanced glycation end-product formation and induction of autoimmunity.
Vytásek
Richard
R
Department of Medical Chemistry and Biochemistry, 2nd Faculty of Medicine, Charles University, V Uvalu 84, Praha, CZ-150 06, Czech Rep.
Sedová
Liliana
L
Vilím
Vladimír
V
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000302:isolation & purification; D000941:Antigens / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000276:immunology* / Q000503:physiopathology; D005260:Female; D017127:Glycation End Products, Advanced / Q000032:analysis* / Q000097:blood*; D006801:Humans; D007124:Immunoenzyme Techniques / Q000379:methods*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000175:diagnosis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000097:blood / Q000175:diagnosis / Q000276:immunology; D017063:Outcome Assessment, Health Care; D011237:Predictive Value of Tests; D012217:Rheumatoid Factor / Q000032:analysis / Q000097:blood; D012720:Severity of Illness Index
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D000941:Antigens; D017127:Glycation End Products, Advanced; D012217:Rheumatoid Factor