CD4(+) T cells predominate in cerebrospinal fluid and leptomeningeal and parenchymal infiltrates in cerebral amyloid β-related angiitis

Abstract

Background: In amyloid (Aβ)-related angiitis (ABRA)of the central nervous system (CNS), cerebral amyloid angiopathy occurs in association with primary vasculitis of small- and medium-sized leptomeningeal and cortical arteries. It has been suggested that ABRA is triggered by vascular deposition of A followed by an Aβ-directed (auto)immune response.

Objective: To provide a detailed description of the cellular composition of the inflammatory infiltrates in the cerebrospinal fluid (CSF) and CNS and their response to immunotherapy in a typical case of ABRA.

Design: Report of a single case.

Setting: Neurologic referral center.

Patient: 67-year-old white woman.

Main outcome measures: Neurologic examination,magnetic resonance imaging, lumbar puncture, flow cytometry,leptomeningeal biopsy, and histopathologic analysis.

Results: In a typical case of ABRA, we demonstrate for the first time the presence of a vast majority of partially activated CD4(+) T cells in CSF and leptomeningeal and parenchymal (peri)vascular infiltrates, which were frequently found in close proximity to major histocompatibility complex (MHC) class II-expressing microglia, epithelioid macrophages, and multinucleated giant cells containing intracellular deposits of Aβ.

Conclusion: Our findings support the notion of adaptive Aß-directed autoimmunity as the underlying pathogenic mechanism in ABRA.