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

BMC Musculoskeletal Disorders

Raimon Sanmartí¹  Raúl Castellanos-Moreira¹  Simón Sánchez-Fernández²  Antonio Fernández-Nebro³  Ma Luz García Vivar⁴  Mercedes Alperi⁵  Isidoro González⁶  Antonio Juan Mas⁷  César Díaz-Torné⁸  Jordi Monfort⁹  Francisco Blanco^1,10  Núria Palau^1,11  Antonio Julià^1,11  Sara Marsal^1,11  Antonio Gómez^1,11  María López-Lasanta^1,11  Alba Erra^1,11  Raquel Lastra^1,11  Jordi Lladós^1,11  Isabel Haro^1,12 

[1] Rheumatology Department, Fundació Clínic Recerca Biomèdica, Barcelona, Spain;Rheumatology Department, Hospital General La Mancha Centro, Ciudad Real, Spain;Rheumatology Department, Hospital Regional Universitario de Málaga, Málaga, Spain;Rheumatology Department, Hospital Universitario Basurto, Bilbao, Spain;Rheumatology Department, Hospital Universitario Central de Asturias, Oviedo, Spain;Rheumatology Department, Hospital Universitario La Princesa, Madrid, Spain;Rheumatology Department, Hospital Universitario Son Llàtzer, Mallorca, Spain;Rheumatology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain;Rheumatology Department, Hospital del Mar, Barcelona, Spain;Rheumatology Department, INIBIC-Hospital Universitario A Coruña, A Coruña, Spain;Rheumatology Research Group, Vall d’Hebron University Hospital Research Institute, 08035, Barcelona, Spain;Unitat de Síntesi i Aplicacions Biomèdiques de Pèptids, IQAC-CSIC, Barcelona, Spain;

关键词: Rheumatoid arthritis;    Treatment response;    Anti-TNF therapy;    Autoantibodies;   

DOI  :  10.1186/s12891-021-04248-y

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY