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Decreased IgG4 ACPA levels in responders and increased CD1c+ classical dendritic cells in non-responders of patients with rheumatoid arthritis under therapy

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Abstract

The treatment options for patients suffering from rheumatoid arthritis expanded over the last years. However, reliable biomarkers to guide therapy decisions are still warranted. Therefore, we here evaluated the value of antibodies against citrullinated peptide antigens (ACPA) IgG subclasses and peripheral blood antigen presenting cells as biomarkers to monitor and predict therapy response of patients with rheumatoid arthritis. Thirty-four ACPA-positive RA patients were enrolled and monitored for 3 months after therapy begin. ACPA IgG1 and IgG4 serum levels were quantified by ELISA. Phenoty** of the B cell, monocytic, and dendritic cell lineages was performed via flow cytometry. Three months after therapy begin, the responders showed a significant decrease in IgG4 ACPA levels, and this was independent of the individual treatment regimen. The non-responders showed a significant increase in CD1c+ classical dendritic cells (cDC). Furthermore, the baseline disease activity score 28 and the baseline percentage of cDC allowed for some prediction of future therapy responses. We here suggest IgG4 ACPA levels as biomarkers to monitor therapy response in RA. The increase in CD1c+ cDC among non-responders to therapy remains enigmatic and requires future elucidation of the underlying mechanisms.

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Acknowledgements

We thank Matthias Richter for providing patient samples and data.

Funding

This work was supported by the Pfizer Inc. under grant number WI170970. The funding agency had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Institute of Immunology, Rostock University Medical Center, Schillingallee 70, 18057, Rostock, Germany

    Robby Engelmann, Sven Nekarda, Daniela Kuthning & Brigitte Müller-Hilke

  2. Klinikum Südstadt Rostock, Südring 81, 18059, Rostock, Germany

    Christian Kneitz

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  1. Robby Engelmann
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Correspondence to Robby Engelmann.

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Conflict of interest

This work was supported by the Pfizer Inc. The funding agency had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. C.K. received consulting and lecture fees from Pfizer Inc. All other authors have no further financial relationship with the sponsor and declare no additional conflicts of interest.

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Engelmann, R., Nekarda, S., Kuthning, D. et al. Decreased IgG4 ACPA levels in responders and increased CD1c+ classical dendritic cells in non-responders of patients with rheumatoid arthritis under therapy. Clin Rheumatol 37, 1783–1790 (2018). https://doi.org/10.1007/s10067-018-4053-y

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  • DOI: https://doi.org/10.1007/s10067-018-4053-y

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