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 (anti...

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Authors: 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
Format: Article
Status:Published version
Publication date:2021
Country:España
Institution:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repository:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p4802
Online Access:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4802
https://ddd.uab.cat/record/271995
Access Level:Open access
Keyword:Rheumatoid arthritis
Treatment response
Anti-TNF therapy
Autoantibodies
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author Julia, A
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author_browse Alperi, M
Blanco, F
Castellanos-Moreira, R
Diaz-Torne, C
Erra, A
Fernandez-Nebro, A
Gomez, A
Gonzalez, I
Haro, I
Julia, A
Lastra, R
Llados, J
Lopez-Lasanta, M
Marsal, S
Mas, AJ
Monfort, J
Palau, N
Sanchez-Fernandez, S
Sanmarti, R
Vivar, MLG
author_facet 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
author_role author
collection r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
description 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.
eu_rights_str_mv openAccess
format article
id ES_3c625f0ea386d6bb8dc51d55ea2d1fdc
institution Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
network_acronym_str ES
network_name_str España
oai_identifier_str oai:iibsantpau.fundanetsuite.com:p4802
publishDate 2021
publishDateSort 2021
publisher BMC
publisherStr BMC
reponame_str r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
spelling Interactions between rheumatoid arthritis antibodies are associated with the response to anti-tumor necrosis factor therapy 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 Rheumatoid arthritis Treatment response Anti-TNF therapy Autoantibodies 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. BMC https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4802 https://ddd.uab.cat/record/271995
spellingShingle Interactions between rheumatoid arthritis antibodies are associated with the response to anti-tumor necrosis factor therapy
Julia, A
Rheumatoid arthritis
Treatment response
Anti-TNF therapy
Autoantibodies
status_str publishedVersion
title Interactions between rheumatoid arthritis antibodies are associated with the response to anti-tumor necrosis factor therapy
title_full Interactions between rheumatoid arthritis antibodies are associated with the response to anti-tumor necrosis factor therapy
title_fullStr Interactions between rheumatoid arthritis antibodies are associated with the response to anti-tumor necrosis factor therapy
title_full_unstemmed Interactions between rheumatoid arthritis antibodies are associated with the response to anti-tumor necrosis factor therapy
title_short Interactions between rheumatoid arthritis antibodies are associated with the response to anti-tumor necrosis factor therapy
title_sort Interactions between rheumatoid arthritis antibodies are associated with the response to anti-tumor necrosis factor therapy
topic Rheumatoid arthritis
Treatment response
Anti-TNF therapy
Autoantibodies
topic_facet Rheumatoid arthritis
Treatment response
Anti-TNF therapy
Autoantibodies
url https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4802
https://ddd.uab.cat/record/271995