No replicating evidence for anti-amyloid-β autoantibodies in cerebral amyloid angiopathy-related inflammation.

Autor: van den Berg E; Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands., Roelofs R; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands., Jäkel L; Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands., Greenberg SM; Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA., Charidimou A; Department of Neurology, Boston University Medical Center, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA., van Etten ES; Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands., Boche D; Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK., Klijn CJM; Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands., Schreuder FHBM; Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands., Kuiperij HB; Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands., Verbeek MM; 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.
Jazyk: angličtina
Zdroj: Annals of clinical and translational neurology [Ann Clin Transl Neurol] 2024 Oct; Vol. 11 (10), pp. 2563-2571. Date of Electronic Publication: 2024 Sep 13.
DOI: 10.1002/acn3.52169
Abstrakt: Objective: 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.
Methods: 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.
Results: The assay demonstrated a high background signal in CSF, which increased and corresponded with higher total immunoglobulin G (IgG) concentration in CSF (r sp  = 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.
Interpretation: 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.
(© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
Databáze: MEDLINE
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