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BDNF in RA: Downregulated in plasma following anti-TNF treatment but no correlation with inflammatory parameters

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Abstract

The involvement of brain-derived neurotrophic factor (BDNF) in rheumatoid arthritis (RA) is largely unknown. The distribution of BDNF and its associated receptors, TrkB and p75, in the synovial tissue of patients with RA was examined and contrasted with that in patients with osteoarthritis (OA). Additionally, levels of BDNF in both synovial tissue and synovial fluid were measured. Furthermore, the effects of anti-tumour necrosis factor (anti-TNF; infliximab) treatment on BDNF levels in the plasma of RA patients were analysed. Cells in the synovium showed immunoreactivity for BDNF and BDNF-, p75- and TrkB-receptor immunoreactions were seen in nerve fibres of nerve fascicles and in association with sensory corpuscles. The levels of BDNF in synovial tissue were not correlated with the number of inflammatory cells observed microscopically or with levels of TNFα. Nor did the BDNF levels in synovial fluid correlate with erythrocyte sedimentation rate (ESR) or white blood cell counts. Anti-TNF treatment lead to a decrease in plasma levels of BDNF 14 weeks after the initiation of anti-TNF therapy, i.e., 8 weeks after the last infusion. Higher levels of BDNF were observed in RA patients at baseline compared with those for healthy individuals. However, the levels of BDNF in plasma of patients treated with anti-TNF did not correlate with the changes in ESR or a disease activity score. The clinical significance of this study is that anti-TNF treatment influences plasma levels of BDNF although there was no evidence that BDNF levels correlate with inflammatory parameters in either infliximab-treated or non-infliximab-treated patients with RA. Instead it is likely that sources other than inflammatory cells, including nerve structures, are important sources of BDNF and that the effects of anti-TNF treatment on BDNF levels may be related to effects on circulating and various local cells and/or BDNF-containing neurons.

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Acknowledgements

We thank Ms Ulla Hedlund and Ms Lena Jonsson for excellent technical assistance. The authors are also grateful to MD Solveig Wållberg-Jonsson for contributing to the collection of samples. We thank Dr. Brian Ellis for linguistic revision of the manuscript. The study was supported by the Faculty of Medicine, Umeå University.

Disclosure

Ola Grimsholm: None; Solbritt Rantapaa-Dahlqvist: None; Tore Dalen: None; Sture Forsgren: None.

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Authors and Affiliations

  1. Department of Integrative Medical Biology, Section for Anatomy, Umeå University, Umeå, Sweden

    Ola Grimsholm & Sture Forsgren

  2. Department of Rheumatology, Umeå University Hospital, Umeå, Sweden

    Solbritt Rantapää-Dahlqvist

  3. Department of Orthopaedics, Umeå University Hospital, Umeå, Sweden

    Tore Dalén

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  1. Ola Grimsholm
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  2. Solbritt Rantapää-Dahlqvist
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  3. Tore Dalén
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  4. Sture Forsgren
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Correspondence to Ola Grimsholm.

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Grimsholm, O., Rantapää-Dahlqvist, S., Dalén, T. et al. BDNF in RA: Downregulated in plasma following anti-TNF treatment but no correlation with inflammatory parameters. Clin Rheumatol 27, 1289–1297 (2008). https://doi.org/10.1007/s10067-008-0910-4

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  • DOI: https://doi.org/10.1007/s10067-008-0910-4

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