Background/Purpose: Hypertrophic pachymeningitis (HP), which becomes the cause of chronic headache, seizure, and cranial neuropathy, is an inflammatory disorder demonstrating focal and diffuse thickening of dura mater. It has been recognized that ANCA-associated vasculitis is the underlying disease as the common cause of HP whose histopathology indicates inflammatory cells infiltration and granulomatous lesion as well as fibrosis; meanwhile, definite immune-mediated mechanism is still elusive. In this study, we demonstrated the useful cerebrospinal fluid (CSF) biomarkers in ANCA-related HP (ANCA-HP).

Methods: We reviewed the clinical records of 22 Japanese patients with immune-mediated HP (mean age, 65 years; 9 women and 13 men). They were divided into patients with ANCA-HP (n = 11), or those with other autoimmune disorders related HP (other HP) including IgG4-related disease/multifocal fibrosclerosis (n = 4), relapsing polychondritis (n = 1), sarcoidosis (n = 2), and idiopathic HP (n = 4). HP associated with infection and/or neoplasm was excluded in this study. As the controls, 11 patients with multiple sclerosis (MS) and 8 with non-inflammatory neurological disorders (NIND) were enrolled. The routine laboratory examinations of serum C-reactive protein (CRP) levels and CSF, including cell counts, protein levels, and IgG-index were detected. In addition, B-cell activation factor of the TNF family (BAFF) and a proliferation-inducing ligand (APRIL) in the CSF and serum samples were measured using commercially available ELISA kits. To determine the characteristics of ANCA-HP, the laboratory data from them were statistically compared between patients with ANCA-HP, other HP, and controls.

Results: CSF levels of BAFF and APRIL were significantly higher in patients with both ANCA-HP and other HP than in patients with MS and NIND (p < 0.05). Serum levels of BAFF and APRIL were significantly higher in patients with both ANCA-HP and other HP than in patients with NIND (p < 0.05). In patients with both ANCA-HP and other HP, neither BAFF nor APRIL expression indicated no correlation between in the CSF and serum, suggesting that BAFF and APRIL were locally produced within the central nervous system (CNS). Meanwhile, both BAFF and APRIL expression in the CSF significantly demonstrated the correlation with IgG-index in patients with ANCA-HP (p < 0.05). In patients with other HP, BAFF and APRIL expression in the CSF had significant correlation with cell counts and protein levels (p < 0.05).

Conclusion: BAFF and APRIL expression in the CSF is associated with disease activity as the immunological biomarker in immune-mediated HP. Furthermore, it was suggested that increased levels of BAFF and APRIL produced in the CNS may impact on developing ANCA-HP by promoting the B cell lineage.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/cerebrospinal-fluid-biomarker-of-disease-activity-significance-in-anca-related-hypertrophic-pachymeningitis/