In rheumatoid arthritis, changes in autoantibody levels reflect intensity of immunosuppression, not subsequent treatment response

Arthritis Research & Therapy

Leroy R. Lard¹  Gerard Collée¹  Tom W. J. Huizinga²  Diane van der Woude²  Sofia Ramiro²  René E. M. Toes²  Cornelia F. Allaart²  Emma C. de Moel²  Veerle F. A. M. Derksen²  Leendert A. Trouw²  Holger Bang³ 

[1] Haaglanden Medical Center Antoniushove;Leiden University Medical Center;Orgentec Diagnostika GmbH;

关键词: Rheumatoid arthritis;    Autoantibodies;    Ant-CCP2;    Rheumatoid factor;    Anti-carbamylated protein antibodies;    Disease activity;   

DOI  :  10.1186/s13075-019-1815-0

来源: DOAJ

【 摘 要 】

Abstract Background Rheumatoid arthritis (RA) is characterized by the presence of autoantibodies like rheumatoid factor (RF), anti-cyclic citrullinated peptide-2 (anti-CCP2), and anti-carbamylated protein (anti-CarP) antibodies. It is currently unclear whether changes in autoantibody levels are associated with disease activity/treatment outcomes and whether they are modified by treatment intensity. Therefore, we determined longitudinal changes in RA-autoantibody levels, the association between these changes and activity score (DAS) and treatment outcomes, and the effect of intensity of immunosuppressive treatment on levels. Methods In 381 seropositive RA patients from the IMPROVED study, we measured IgG, IgM, and IgA of anti-CCP2 and anti-CarP; IgM and IgA of RF; and IgG against four citrullinated and two acetylated peptides at 4-month intervals over the first year of treatment. Following initial prednisone and methotrexate (MTX), treatment was changed every 4 months aiming for DAS < 1.6. We investigated changes in autoantibody levels following treatment escalation versus tapering, and the association of levels with DAS over time, EULAR response, and drug-free remission (DFR) ≥ 1 year. Results For all 14 autoantibodies, levels decreased from 0 to 4 months and then rose until 12 months. Following treatment escalation, autoantibody levels dropped markedly, while they rose following tapering: RF IgM levels, a representative autoantibody, dropped 10% after restarting prednisone and rose 15% aU/mL after tapering MTX (p < 0.0001). There was no association between autoantibody levels and DAS over time or EULAR response. Greater relative changes between 0 and 12 months did not predict DFR (0–12-month relative change RF IgM, − 39% for no DFR (n = 126) and − 16% for DFR (n = 18)). Conclusions Changes in RA-autoantibody levels are not associated with DAS or long-term treatment response, but reflect intensity of immunosuppression. This suggests that autoantibody levels are modifiable by current therapies, but that modifying levels is in itself of limited clinical relevance. Trial registration ISRCTN11916566. Registered on 7 November 2006

【 授权许可】

Unknown