Abstract
BackgroundLevels 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.MethodsWe 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 Nε-(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.ResultsLevels 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 Nε-(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.ConclusionsWe 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.
Highlights
Levels of pentosidine in sera of patients with rheumatoid arthritis are increased when compared with sera of other diagnoses or healthy controls
All studies aimed at measuring advanced glycation end-products (AGE) levels in serum or plasma of patients with rheumatoid arthritis (RA) have been limited to exclusively measuring pentosidine using high-performance liquid chromatography (HPLC) [4,5,6,7,8,9,10,11,12]
Takahashi et al [4] concluded that the level of pentosidine in sera of RA patients reflects the activity of the disease, as the serum level of pentosidine correlated with clinical indices of RA activity, as well as with levels of serum markers of inflammation (CRP, ESR) and the level of rheumatoid factor (RF)
Summary
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. Pentosidine levels in plasma of RA patients were compared with levels in plasma of patients with OA, with levels in plasma of patients with diabetes, and with levels in plasma of normal subjects [12] Each of these studies reported an increased mean level of pentosidine in RA serum/plasma. Takahashi et al [4] concluded that the level of pentosidine in sera of RA patients reflects the activity of the disease, as the serum level of pentosidine correlated with clinical indices of RA activity, as well as with levels of serum markers of inflammation (CRP, ESR) and the level of rheumatoid factor (RF)
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