Interactions between rheumatoid arthritis antibodies are associated with the response to anti-tumor necrosis factor therapy
Por:
Julia, A, Lopez-Lasanta, M, Blanco, F, Gomez, A, Haro, I, Mas, AJ, Erra, A, Vivar, MLG, Monfort, J, Sanchez-Fernandez, S, Gonzalez, I, Alperi, M, Castellanos-Moreira, R, Fernandez-Nebro, A, Diaz-Torne, C, Palau, N, Lastra, R, Llados, J, Sanmarti, R, Marsal, S
Publicada:
21 abr 2021
Resumen:
Background Blocking 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. Methods For 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. Results The 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). Conclusions The results of this study suggest that antibody interaction effects are important factors in the response to anti-TNF therapy in RA.
Filiaciones:
Julia, A:
Vall dHebron Univ Hosp Res Inst, Rheumatol Res Grp, Barcelona 08035, Spain
Lopez-Lasanta, M:
Vall dHebron Univ Hosp Res Inst, Rheumatol Res Grp, Barcelona 08035, Spain
Blanco, F:
INIBIC Hosp Univ A Coruna, Rheumatol Dept, La Coruna, Spain
Gomez, A:
Vall dHebron Univ Hosp Res Inst, Rheumatol Res Grp, Barcelona 08035, Spain
Haro, I:
Vall dHebron Univ Hosp Res Inst, Rheumatol Res Grp, Barcelona 08035, Spain
IQAC CSIC, Unitat Sintesi & Aplicac Biomed Peptids, Barcelona, Spain
Mas, AJ:
Hosp Univ Son Llatzer, Rheumatol Dept, Mallorca, Spain
Erra, A:
Vall dHebron Univ Hosp Res Inst, Rheumatol Res Grp, Barcelona 08035, Spain
Vivar, MLG:
Hosp Univ Basurto, Rheumatol Dept, Bilbao, Spain
Monfort, J:
Hosp del Mar, Rheumatol Dept, Barcelona, Spain
Sanchez-Fernandez, S:
Hosp Gen La Mancha Ctr, Rheumatol Dept, Ciudad Real, Spain
Gonzalez, I:
Hosp Univ La Princesa, Rheumatol Dept, Madrid, Spain
Alperi, M:
Hosp Univ Cent Asturias, Rheumatol Dept, Oviedo, Spain
Castellanos-Moreira, R:
Fundacio Clin Recerca Biomed, Rheumatol Dept, Barcelona, Spain
Fernandez-Nebro, A:
Hosp Reg Univ Malaga, Rheumatol Dept, Malaga, Spain
Diaz-Torne, C:
Hosp Santa Creu & Sant Pau, Rheumatol Dept, Barcelona, Spain
Palau, N:
Vall dHebron Univ Hosp Res Inst, Rheumatol Res Grp, Barcelona 08035, Spain
Lastra, R:
Vall dHebron Univ Hosp Res Inst, Rheumatol Res Grp, Barcelona 08035, Spain
Llados, J:
Vall dHebron Univ Hosp Res Inst, Rheumatol Res Grp, Barcelona 08035, Spain
Sanmarti, R:
Fundacio Clin Recerca Biomed, Rheumatol Dept, Barcelona, Spain
Marsal, S:
Vall dHebron Univ Hosp Res Inst, Rheumatol Res Grp, Barcelona 08035, Spain
Green Published, gold, Green Submitted
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