Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
Department of Laboratory Medicine, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
Clin Rheumatol. 2020 Jun;39(6):1803-1811. doi: 10.1007/s10067-020-04971-2. Epub 2020 Feb 8.
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).
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.
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.
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.
抗中性粒细胞胞质抗体（ANCA）相关肥厚性硬脑膜炎（HP）是最常见的免疫介导性 HP。我们研究了与 ANCA 相关 HP（ANCA-HP）发病机制相关的脑脊液（CSF）生物标志物。
比较了 12 例 ANCA-HP 患者、12 例其他类型免疫介导性 HP（其他 HP）、14 例多发性硬化症（MS）和 10 例非炎症性神经疾病（NIND）患者的 CSF 中 B 细胞激活因子肿瘤坏死因子家族（BAFF）、增殖诱导配体（APRIL）和转化生长因子β 1（TGF-β1）水平。此外，我们评估了 CSF 中是否会检测到 ANCA。
ANCA-HP 和其他 HP 的 CSF 中 BAFF、APRIL 和 TGF-β1 水平均显著升高。特别是，BAFF 和 APRIL 水平与 ANCA-HP 的 IgG 指数显著相关。在其他 HP 中，BAFF 和 APRIL 水平与 CSF 中的细胞计数和蛋白水平显著相关。在 12 例 ANCA-HP 患者中，7 例（58%）患者的 CSF 检测到髓过氧化物酶（MPO）或蛋白酶 3（PR3）-ANCA 阳性，而其他 HP、MS 或 NIND 患者的 CSF 样本均未检测到阳性。
BAFF、APRIL 和 TGF-β1 水平可作为评估免疫介导性 HP 疾病活动的有用 CSF 标志物。此外，CSF 中的 BAFF 和 APRIL 可能通过促进自身反应性 B 细胞参与 ANCA-HP 的发病机制，而在一些 ANCA-HP 患者的 CSF 中可检测到 MPO 或 PR3-ANCA。
CSF BAFF、APRIL 和 TGF-β1 水平在免疫介导性 HP 中显著升高。
CSF BAFF 和 APRIL 水平与 ANCA-HP 中的 IgG 指数显著相关。
在一些 ANCA-HP 患者的 CSF 中检测到 MPO 或 PR3-ANCA。
CSF 中的 BAFF、APRIL 和 ANCA 可能与 ANCA-HP 的发病机制有关。
