Vendrely Aurélie, Bienvenu Boris, Gasnault Jacques, Thiebault Jean Baptiste, Salmon Dominique, Gray Françoise
Service Central d'Anatomie et de Cytologie Pathologiques, AP-HP Hôpital Lariboisière, 2 rue Ambroise Paré, 75475 Paris, France.
Acta Neuropathol. 2005 Apr;109(4):449-55. doi: 10.1007/s00401-005-0983-y. Epub 2005 Mar 1.
HAART-induced immune restoration is beneficial for patients with AIDS-related progressive multifocal leukoencephalopathy (PML). However, in rare instances, an immune-reconstitution inflammatory syndrome (IRIS) may cause paradoxical clinical deterioration. We report the neuropathological study of an AIDS patient who presented with progressive cognitive deterioration; CD4(+) count was 117 and the HIV viral load >10(4); imaging showed non-enhancing lesions consistent with PML. Following initiation of HAART, CD4(+) was 300 and HIV viral load <10(3), but his neurological symptoms continued to deteriorate. Imaging revealed an increase in the size and number of lesions and enhancement of all the lesions. A stereotactic biopsy showed severe inflammatory and demyelinating lesions with marked infiltration by macrophages and T lymphocytes in the absence of a detectable infectious agent. Despite high doses of steroids, the patient died 3 months after admission. Autopsy showed two types of lesions: (1) active inflammatory PML changes with abundant JC virus, and intraparenchymal and perivascular infiltration by T lymphocytes, and (2) acute perivenous leukoencephalitis devoid of JC virus. Most lymphocytes were CD8(+) lymphocytes; CD4(+) lymphocytes were virtually absent. Two pathological reactions were associated with the paradoxical clinical deterioration related to dysregulation of the immune response characteristic of IRIS in PML: (1) an accentuation of JCV infection, and (2) a nonspecific acute perivenous leukoencephalitis. We suggest that both these types of lesions are due to an imbalance of CD8(+)/CD4(+) T cells, with massive infiltration of the cerebral parenchyma by CD8(+) cytotoxic T lymphocytes in the absence of sufficient CD4(+) response. Better understanding of the mechanisms of the IRIS may enable prevention or cure of this severe, sometimes fatal complication of HAART.
高效抗逆转录病毒治疗（HAART）诱导的免疫恢复对艾滋病相关的进行性多灶性白质脑病（PML）患者有益。然而，在罕见情况下，免疫重建炎症综合征（IRIS）可能导致矛盾的临床恶化。我们报告了一名艾滋病患者的神经病理学研究，该患者出现进行性认知衰退；CD4(+)计数为117，HIV病毒载量>10(4)；影像学显示与PML一致的无强化病变。开始HAART治疗后，CD4(+)为300，HIV病毒载量<10(3)，但他的神经症状持续恶化。影像学显示病变大小和数量增加，所有病变均有强化。立体定向活检显示严重的炎症和脱髓鞘病变，巨噬细胞和T淋巴细胞明显浸润，未检测到感染因子。尽管使用了高剂量的类固醇，患者在入院后3个月死亡。尸检显示两种类型的病变：（1）伴有大量JC病毒的活动性炎症性PML改变，以及T淋巴细胞的实质内和血管周围浸润，（2）无JC病毒的急性静脉周围性白质脑炎。大多数淋巴细胞为CD8(+)淋巴细胞；几乎没有CD4(+)淋巴细胞。两种病理反应与PML中IRIS特征性免疫反应失调相关的矛盾临床恶化有关：（1）JCV感染加重，（2）非特异性急性静脉周围性白质脑炎。我们认为这两种类型的病变都是由于CD8(+)/CD4(+) T细胞失衡，在没有足够CD4(+)反应的情况下，CD8(+)细胞毒性T淋巴细胞大量浸润脑实质。更好地理解IRIS的机制可能有助于预防或治愈HAART这种严重的、有时致命的并发症。
