Chen Jiamin, Du Yanni, Sun Lei, Dai Yuyang, Zhang Liang, Ding Xinghuan, Liu Ting, Yang Kun, Han Xiaoyi, Li Man, Zhou Xingang
Department of Pathology, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
Department of Radiology, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
Front Cell Infect Microbiol. 2025 Jun 27;15:1607428. doi: 10.3389/fcimb.2025.1607428. eCollection 2025.
Progressive multifocal leukoencephalopathy (PML), caused by John Cunningham (JC) virus reactivation, represents a critical neurological complication in AIDS-related immunosuppression. This single-center study conducted a clinicopathological analysis of 19 confirmed PML cases in an AIDS cohort (16 biopsy; 3 surgical specimens), employing comprehensive neuropathological evaluation. Immunohistochemical testing included SV40, NF, NeuN, P53, Ki-67, GFAP, Oligo-2, and CD68. Myelin architecture was evaluated through Luxol fast blue staining, complemented by molecular diagnostics incorporating quantitative JC viral load PCR and metagenomic next-generation sequencing (mNGS).
Notably, 63.2% (12/19) of them had blood CD4+ T-cell counts < 200 cells/μl, and 36.8% (7/19) had ≥ 200 cells/μl. 52.9% (9/17) of the patients had elevated CSF protein, 5.3% (1/19) had decreased CSF glucose. Statistical analysis revealed significant correlations between mass effect and both blood CD4+ T-cell counts ( = 0.022) and CSF protein levels ( < 0.001). It also demonstrated significant positive correlations between the duration of HIV diagnosis and the degree of inflammatory infiltration ( = 0.038) and perivascular inflammatory infiltration ( = 0.005), as well as plasma cell infiltration ( = 0.011). The degree of inflammatory infiltration was significantly positively correlated with antiretroviral therapy (ART) ( = 0.036). The degree of inflammatory infiltration, the presence of plasma cells, and perivascular lymphocytic cuffing were significantly associated with contrast enhancement on imaging studies ( = 0.044, = 0.011, and = 0.018, respectively). These cases display characteristics that deviate from the classic PML previously reported, exhibiting a tendency towards MRI enhancement and histologically indicating a more severe inflammatory response, especially for patients following ART treatment.
Our findings suggest that PML and PML-immune reconstitution inflammatory syndrome (IRIS) represent a continuous pathological spectrum, potentially bridged by an intermediate stage with distinct clinicopathological features. This transitional phase may constitute a critical link in the continuum between classic PML and fully developed PML-IRIS. Importantly, it implicates synergistic mechanisms of viral oncogenesis and immune reconstitution, which could redefine therapeutic strategies for this emerging PML variant.
由约翰·坎宁安（JC）病毒再激活引起的进行性多灶性白质脑病（PML）是艾滋病相关免疫抑制中的一种严重神经并发症。这项单中心研究对一个艾滋病队列中的19例确诊PML病例（16例活检；3例手术标本）进行了临床病理分析，采用了全面的神经病理学评估。免疫组织化学检测包括SV40、NF、NeuN、P53、Ki-67、GFAP、Oligo-2和CD68。通过Luxol固蓝染色评估髓鞘结构，并辅以结合定量JC病毒载量PCR和宏基因组下一代测序（mNGS）的分子诊断。
值得注意的是，其中63.2%（12/19）的患者血液CD4+T细胞计数<200个细胞/μl，36.8%（7/19）的患者≥200个细胞/μl。52.9%（9/17）的患者脑脊液蛋白升高，5.3%（1/19）的患者脑脊液葡萄糖降低。统计分析显示占位效应与血液CD4+T细胞计数（=0.022）和脑脊液蛋白水平（<0.001）之间存在显著相关性。它还表明HIV诊断持续时间与炎症浸润程度（=0.038）、血管周围炎症浸润（=0.005）以及浆细胞浸润（=0.011）之间存在显著正相关。炎症浸润程度与抗逆转录病毒治疗（ART）显著正相关（=0.036）。炎症浸润程度、浆细胞的存在以及血管周围淋巴细胞套袖与影像学研究中的对比增强显著相关（分别为=0.044、=0.011和=0.018）。这些病例表现出与先前报道的经典PML不同的特征，表现出MRI增强的趋势，并且组织学上显示炎症反应更严重，尤其是接受ART治疗的患者。
我们的研究结果表明，PML和PML免疫重建炎症综合征（IRIS）代表了一个连续的病理谱，可能由具有独特临床病理特征的中间阶段连接。这个过渡阶段可能构成经典PML和完全发展的PML-IRIS之间连续统一体的关键环节。重要的是，它暗示了病毒致癌和免疫重建的协同机制，这可能重新定义这种新兴PML变体的治疗策略。
