Interactions between rheumatoid arthritis antibodies are associated with the response to anti-tumor necrosis factor therapy

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 (ant...

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Autores: Julià Cano, Antonio|||0000-0001-6064-3620, López Lasanta, María|||0000-0002-8462-8406, Blanco-García, F.J.|||0000-0001-9821-7635, Gómez Moruno, Antonio|||0000-0001-5308-981X, Haro, Immaculada, Mas, Antonio Juan, Erra Duran, Alba|||0000-0001-7806-1098, García Vivar, María Luz|||0000-0001-8822-9843, Monfort, Jordi|||0000-0002-9103-661X, Sánchez-Fernández, Simón, González, Isidoro, Alperi-López, Mercedes, Castellanos-Moreira, Raúl|||0000-0002-4104-4101, Fernández-Nebro, Antonio|||0000-0002-2962-9844, Diaz-Torne, Cesar|||0000-0001-6275-7699, Palau, Núria, Lastra, Raquel, Lladós, Jordi, Sanmartí, Raimon|||0000-0002-8864-3806, Marsal, Sara|||0000-0001-5515-3854
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:271995
Acceso en línea:https://ddd.uab.cat/record/271995
https://dx.doi.org/urn:doi:10.1186/s12891-021-04248-y
Access Level:acceso abierto
Palabra clave:Rheumatoid arthritis
Treatment response
Anti-TNF therapy
Autoantibodies
Descripción
Sumario: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.

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