Leiden University Scholarly Publications

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Moel, E.C. de (2026)

The value of rheumatoid arthritis autoantibodies in disease pathogenesis and treatment prognosis

Doctoral Thesis
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the presence of diverse autoantibodies termed anti-modified protein antibodies (AMPAs) which can be detected years before disease onset and are associated with more severe disease. Their role in treatment prognosis and disease pathogenesis is however not yet known.

This thesis investigated the diversity, dynamics, and clinical relevance of autoantibody profiles in RA. We demonstrated that a broader AMPA profile is associated with a better early treatment response, but not with improved long-term outcomes or drug-free remission (DFR). Longitudinal analyses showed that changes in autoantibody levels largely reflect immunosuppressive treatment rather than underlying disease activity, and seroconversion to autoantibody negativity does indicate a form of immunological remission that is favorable for sustained DFR.

In addition, we showed that AMPA responses vary across populations but converge...Show moreRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the presence of diverse autoantibodies termed anti-modified protein antibodies (AMPAs) which can be detected years before disease onset and are associated with more severe disease. Their role in treatment prognosis and disease pathogenesis is however not yet known.

This thesis investigated the diversity, dynamics, and clinical relevance of autoantibody profiles in RA. We demonstrated that a broader AMPA profile is associated with a better early treatment response, but not with improved long-term outcomes or drug-free remission (DFR). Longitudinal analyses showed that changes in autoantibody levels largely reflect immunosuppressive treatment rather than underlying disease activity, and seroconversion to autoantibody negativity does indicate a form of immunological remission that is favorable for sustained DFR.

In addition, we showed that AMPA responses vary across populations but converge toward a common immunological endpoint, independent of genetic and environmental risk factors. Finally, studies in cancer patients treated with immune checkpoint inhibitors revealed that induced autoantibody responses differ from those observed in RA, suggesting distinct underlying mechanisms.

Overall, this work highlights that while autoantibodies are central to RA pathogenesis, they have limited value in predicting long-term disease control.
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Rheumatoid arthritis
Anti-modified protein antibodies
AMPA
Rheumatoid factor
RF
Anti-citrullinated
ACPA
Anti-carbamylated
Anti-CarP
Anti-acetylated
AAPA
Calprotectin
Anti-MAA
Immune checkpoint inhibitors
All authors
Moel, E.C. de
Supervisor
Woude, D. van der; Toes, R.E.M.
Committee
Huizinga, T.W.J.; Helm-van Mil, A.H.M. van der; Kooij, S.M. van der; Gelderman, K.A.
Qualification
Doctor (dr.)
Awarding Institution
Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Date
2026-04-07
ISBN (print)
9789465373164

Funding

Sponsorship
The research in this thesis was funded by the Dutch Research Council, ZonMw (the Netherlands Organisation for Health Research and Development; including the MODIRA consortium and a Veni grant), and Inova Diagnostics.