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Cerebrospinal fluid biomarkers implicated in the pathogenesis of anti-neutrophil cytoplasmic antibody-related hypertrophic pachymeningitis

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Abstract

Objective

Hypertrophic pachymeningitis (HP) related to anti-neutrophil cytoplasmic antibody (ANCA) is the most frequently seen immune-mediated HP. We investigated cerebrospinal fluid (CSF) biomarkers related to the pathogenesis of ANCA-related HP (ANCA-HP).

Methods

The levels of B cell activation factor of the tumor necrosis factor family (BAFF), a proliferation-inducing ligand (APRIL), and transforming growth factor beta 1 (TGF-β1) in the CSF were compared between patients with ANCA-HP (n = 12), other types of immune-mediated HP (other HP; n = 12), multiple sclerosis (MS; n = 14), and non-inflammatory neurological disorders (NIND; n = 10). In addition, we evaluated whether ANCA would be detected in CSF.

Results

CSF levels of BAFF, APRIL, and TGF-β1 were significantly increased in ANCA-HP and other HP. In particular, BAFF and APRIL levels were significantly correlated with the IgG index in ANCA-HP. In other HP, BAFF and APRIL levels were significantly correlated with cell counts and protein levels in CSF. Of 12 patients with ANCA-HP, the CSF of 7 patients (58%) tested positive for myeloperoxidase (MPO)- or proteinase 3 (PR3)-ANCA, while none of the CSF samples from other HP, MS, or NIND patients tested positive.

Conclusion

The levels of BAFF, APRIL, and TGF-β1 may serve as useful CSF biomarkers for assessing the disease activity of immune-mediated HP. Moreover, BAFF and APRIL in the CSF may be implicated in the pathogenesis of ANCA-HP via promoting autoreactive B cells, while detecting MPO- or PR3-ANCA in the CSF may be found in some patients with ANCA-HP.

Key Points

• CSF BAFF, APRIL, and TGF-β1 levels increase significantly in immune-mediated HP.

• CSF BAFF and APRIL levels are significantly correlated with IgG index in ANCA-HP.

• Detection of MPO- or PR3-ANCA in the CSF is found in some patients with ANCA-HP.

• BAFF, APRIL, and ANCA in the CSF may be implicated in the pathogenesis of ANCA-HP.

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Acknowledgments

We wish to thank the members of the Department of Medicine (Neurology and Rheumatology) for their efforts providing medical care, Dr. Mitsutoshi Sugano (Department of Laboratory Medicine, Shinshu University Hospital) for their cooperation with the laboratory analysis, and Dr. Masayoshi Koinuma (Center for Clinical Research, Shinshu University Hospital) for his statistical advice.

Funding

This study was supported by a Health and Labour Sciences Research Grant on Rare and Intractable Diseases (Evidence-based Early Diagnosis and Treatment Strategies for Neuroimmunological Diseases) from the Ministry of Health, Labor and Welfare of Japan.

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Authors and Affiliations

  1. Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan

    Junji Ikeda, Yasuhiro Shimojima, Ken-ichi Ueno, Dai Kishida & Yoshiki Sekijima

  2. Department of Laboratory Medicine, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, 390-8621, Japan

    Yoko Usami

  3. Institute for Biomedical Sciences, Shinshu University, 3-1-1 Asahi, Matsumoto, 390-8621, Japan

    Yoshiki Sekijima

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  1. Junji Ikeda
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Correspondence to Yasuhiro Shimojima.

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The present study was approved by the Local Ethics Committee of Shinshu University. Written informed consent was obtained from all participants.

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Ikeda, J., Shimojima, Y., Usami, Y. et al. Cerebrospinal fluid biomarkers implicated in the pathogenesis of anti-neutrophil cytoplasmic antibody-related hypertrophic pachymeningitis. Clin Rheumatol 39, 1803–1811 (2020). https://doi.org/10.1007/s10067-020-04971-2

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