Fulminant inflammatory leukoencephalopathy associated with HAART-induced immune restoration in AIDS-related progressive multifocal leukoencephalopathy.
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.
Vendrely
Aurélie
A
Service Central d'Anatomie et de Cytologie Pathologiques, AP-HP Hôpital Lariboisière, 2 rue Ambroise Paré, 75475 Paris, France.
Bienvenu
Boris
B
Gasnault
Jacques
J
Thiebault
Jean Baptiste
JB
Salmon
Dominique
D
Gray
Françoise
F
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D015703:Antigens, CD / Q000378:metabolism; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count / Q000379:methods; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D007577:JC Virus / Q000502:physiology; D007968:Leukoencephalopathy, Progressive Multifocal / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D019562:Viral Load / Q000379:methods
D015703:Antigens, CD