Abstract
BackgroundBlocking of the Tumor Necrosis Factor (TNF) activity is a successful therapeutic approach for 50–60% of rheumatoid arthritis (RA) patients. However, there are yet no biomarkers to stratify patients for anti-TNF therapy. Rheumatoid factor (RF) and anti-cyclic-citrullinated antibodies (anti-CCP) have been evaluated as biomarkers of response but the results have shown limited consistency. Anti-carbamylated protein (anti-CarP) and anti-peptidylarginine deiminase type 4 (anti-PAD4) antibodies have been much less studied. Despite being linked to common immune processes, the interaction between these markers has not been evaluated yet. Our aim was to analyze the interaction between these four antibodies in relation to the response to anti-TNF therapy.MethodsFor this objective, a prospective cohort of n = 80 RA patients starting anti-TNF therapy was recruited. Serum determinations at baseline were performed for RF, anti-CCP, anti-CarP and anti-PAD4 antibodies using enzyme-linked immunosorbent assays (ELISA). The clinical response to anti-TNF therapy was determined at week 12 using the change in DAS28 score. Association was performed using multivariate linear regression adjusting for baseline DAS28, sex and age.ResultsThe interaction between pairs of antibodies was tested by the addition of an interaction term. We found two highly significant antibody interactions associated with treatment response: anti-CarP with anti-PAD4 (p = 0.0062), and anti-CCP with RF (p = 0.00068). The latter antibody interaction was replicated in an independent retrospective cohort of RA patients (n = 199, p = 0.04).ConclusionsThe results of this study suggest that antibody interaction effects are important factors in the response to anti-TNF therapy in RA.
Highlights
Blocking of the Tumor Necrosis Factor (TNF) activity is a successful therapeutic approach for 50–60% of rheumatoid arthritis (RA) patients
The four autoantibody titers were determined in 100% of the patients. 65% of the RA patients were positive for Rheumatoid factor (RF) and 72% of for anti-CCP
An average reduction of 1.96 (+/− 1.33) points in the Disease Activity Score for 28 joints (DAS28) score was observed for the global cohort, which is consistent with previous studies [15]
Summary
Blocking of the Tumor Necrosis Factor (TNF) activity is a successful therapeutic approach for 50–60% of rheumatoid arthritis (RA) patients. Rheumatoid factor (RF) and anti-cyclic-citrullinated antibodies (anti-CCP) have been evaluated as biomarkers of response but the results have shown limited consistency. Tumor necrosis factor (TNF) is a proinflammatory cytokine that is central to the inflammatory process of RA Systemic blocking of this cytokine has proven to be a highly efficacious approach to control the disease activity [1]. Antibodies against the Fc portion of immunoglobulin G –rheumatoid factor (RF)and against cyclic citrullinated peptides (anti-CCP) are currently the two most relevant diagnostic tests for RA [2]. Both autoantibodies have been clearly associated to unfavorable prognosis [3]. Interest has shifted in analyzing more recently discovered antibodies as potential biomarkers for treatment response
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