Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Ann Clin Transl Neurol. 2024 Oct;11(10):2563-2571. doi: 10.1002/acn3.52169. Epub 2024 Sep 13.
Elevated levels of anti-amyloid-β (anti-Aβ) autoantibodies in cerebrospinal fluid (CSF) have been proposed as a diagnostic biomarker for cerebral amyloid angiopathy-related inflammation (CAA-RI). We aimed to independently validate the immunoassay for quantifying these antibodies and evaluate its diagnostic value for CAA-RI.
We replicated the immunoassay to detect CSF anti-Aβ autoantibodies using CSF from CAA-RI patients and non-CAA controls with unrelated disorders and further characterized its performance. Moreover, we conducted a literature review of CAA-RI case reports to investigate neuropathological and CSF evidence of the nature of the inflammatory reaction in CAA-RI.
The assay demonstrated a high background signal in CSF, which increased and corresponded with higher total immunoglobulin G (IgG) concentration in CSF (r = 0.51, p = 0.02). Assay levels were not elevated in CAA-RI patients (n = 6) compared to non-CAA controls (n = 20; p = 0.64). Literature review indicated only occasional presence of B-lymphocytes and plasma cells (i.e., antibody-producing cells), alongside the abundant presence of activated microglial cells, T-cells, and other monocyte lineage cells. CSF analysis did not convincingly indicate intrathecal IgG production.
We were unable to reproduce the reported elevation of anti-Aβ autoantibody concentration in CSF of CAA-RI patients. Our findings instead support nonspecific detection of IgG levels in CSF by the assay. Reviewed CAA-RI case reports suggested a widespread cerebral inflammatory reaction. In conclusion, our findings do not support anti-Aβ autoantibodies as a diagnostic biomarker for CAA-RI.
脑脊髓液（CSF）中抗淀粉样蛋白-β（anti-Aβ）自身抗体水平升高被认为是脑淀粉样血管病相关炎症（CAA-RI）的一种诊断生物标志物。我们旨在独立验证用于定量检测这些抗体的免疫分析，并评估其对 CAA-RI 的诊断价值。
我们使用 CAA-RI 患者和具有无关疾病的非 CAA 对照的 CSF 复制了该免疫分析，以检测 CSF 中的抗 Aβ 自身抗体，并进一步对其性能进行了特征描述。此外，我们对 CAA-RI 病例报告进行了文献综述，以研究 CAA-RI 中炎症反应的性质的神经病理学和 CSF 证据。
该检测在 CSF 中表现出高背景信号，该信号随着 CSF 中总免疫球蛋白 G（IgG）浓度的升高而增加（r=0.51，p=0.02）。与非 CAA 对照组（n=20）相比，CAA-RI 患者（n=6）的检测水平并未升高（p=0.64）。文献综述表明，除了大量存在活化的小胶质细胞、T 细胞和其他单核细胞谱系细胞外，仅偶尔存在 B 淋巴细胞和浆细胞（即产生抗体的细胞）。CSF 分析并没有令人信服地表明鞘内 IgG 产生。
我们无法复制报告的 CAA-RI 患者 CSF 中抗 Aβ 自身抗体浓度升高的结果。相反，我们的发现支持该检测方法对 CSF 中 IgG 水平的非特异性检测。综述的 CAA-RI 病例报告表明存在广泛的脑炎症反应。总之，我们的研究结果不支持抗 Aβ 自身抗体作为 CAA-RI 的诊断生物标志物。
