关键词: AIDS IFN-γ release assay JC virus effector T cells effector memory T cells multiple sclerosis natalizumab progressive multifocal leukoencephalopathy

Mesh : Humans Leukoencephalopathy, Progressive Multifocal / immunology diagnosis etiology Interferon-gamma Male JC Virus / immunology Female Middle Aged Adult Memory T Cells / immunology metabolism Natalizumab / therapeutic use Aged Multiple Sclerosis / immunology drug therapy

来  源:   DOI:10.3389/fimmu.2024.1416074   PDF(Pubmed)

Abstract:
UNASSIGNED: Progressive Multifocal Leukoencephalopathy (PML) is a rare and deadly demyelinating disease caused by JC virus (JCV) replication in the central nervous system. PML occurs exclusively in patients with severe underlying immune deficiencies, including AIDS and hematological malignancies. PML has also emerged as a significant threat to patients on potent new immunosuppressive biologics, including natalizumab in multiple sclerosis.
UNASSIGNED: Here, we developed an IFN-γ release assay (IGRA) that mainly detects JCV-specific effector memory T cells and effectors T cells in the blood.
UNASSIGNED: This assay was frequently positive in patients with active PML (with a positive JCV PCR in CSF) of various underlying immunosuppression causes (84% sensitivity). Only 3% of healthy donors had a positive response (97% specificity). The frequency of positivity also increased in multiple sclerosis patients according to the time on natalizumab (up to 36% in patients treated for more than 48 months, who are considered at a higher risk of PML).
UNASSIGNED: The results show this assay\'s frequent or increased positivity in patients with PML or an increased risk of PML, respectively. The assay may help to stratify the risk of PML.
摘要:
进行性多灶性白质脑病(PML)是由JC病毒(JCV)在中枢神经系统中复制引起的一种罕见且致命的脱髓鞘疾病。PML仅发生在患有严重潜在免疫缺陷的患者中。包括艾滋病和血液恶性肿瘤。PML也已成为对患者有效的新免疫抑制生物制剂的重大威胁,包括那他珠单抗治疗多发性硬化症。
这里,我们开发了一种IFN-γ释放试验(IGRA),主要检测血液中JCV特异性效应记忆T细胞和效应T细胞。
该测定在具有各种潜在免疫抑制原因的活动性PML(在CSF中具有阳性JCVPCR)的患者中通常为阳性(84%的灵敏度)。只有3%的健康供体具有阳性反应(97%特异性)。根据使用那他珠单抗的时间,多发性硬化症患者的阳性频率也增加了(治疗超过48个月的患者高达36%,被认为患PML的风险较高)。
结果显示,在患有PML或PML的风险增加的患者中,该测定频繁或增加阳性,分别。该测定可能有助于对PML的风险进行分层。
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