Multiple sclerosis and amyloid deposits in the white matter of the brain.

We present the neuropathological findings in a female patient with clinically definite multiple sclerosis (MS), who at autopsy had multifocal amyloid deposits in the white matter of the brain without other signs of amyloidosis. The patient had relapsing/remitting MS between the ages of 26 and 45, and during her last 14 years she had a secondary chronic progressive form of MS. Previous reports of amyloid deposits in MS are reviewed and the possible relationship between amyloid deposits and the increased production of immunoglobulin free light chains in MS is discussed.

Cell association of HIV in AIDS-related encephalopathy and dementia.

The presence of HIV gag and env proteins (HIV Ag) and virus replicating cells was studied by immunohistochemistry and in situ hybridization, respectively, in brain specimens from five HIV infected patients. HIV antigens were detected in 3 of 5 brains in micronodular areas characterized by increased cellularity and the presence of multinuclear giant cells. By double immunostaining, HIV Ag positive cells were shown to express markers common to macrophages and microglia i.e. Leu M5+, My4+, HLA-Dr+, RCA-1+, and to a lesser extent CD4+ (Leu3+). Another macrophage specific marker, KiM6, was found only on HIV+ cells in HIV infected specimens and not in uninfected, control brains. Medium-sized, virus replicating cells were found exclusively in micronodular areas, but in much smaller quantities than HIV Ag+ cells. Our observations provide further evidence to support the hypothesis that macrophages play an important role in CNS infection by HIV and additionally support the concept that reactive microglial originate from activated macrophages infiltrating the brain. Both direct effects of viral components and cell mediated reactions can be implicated from our findings as mechanisms involved in the pathogenesis of the CNS lesions.

HIV encephalopathy and lymphadenopathy: cells associated with viral antigens.

HIV associated subacute, micronodular encephalitis and lymphadenopathy were compared with regard to demonstrable HIV antigens and characterization of HIV antigen expressing cells. In the brain, both gag- and env-coded antigens were confined to cells of micronodular lesions with immunophenotype of monocyte/macrophages (KiM6+, 9.4+, CD4+/-). The micronodular lesions were also infiltrated by some lymphoid cells, predominantly CD8+. In lymphadenopathic nodes, gag-encoded antigens were demonstrable almost exclusively in follicles/germinal centres in association with follicular dendritic cells, whereas env-antigens usually were not found. Follicular involution was related to destruction of follicular dendritic cells and infiltration of CD8+ lymphocytes within the germinal centres. During follicular involution, HIV-gag antigens diminished in parallel with destruction of the network of dendritic reticulum cells. These findings indicate important tissue related differences in HIV expression. In addition, a possible participation of CD8+ cells in the pathogenesis of HIV induced tissue lesions is suggested.

Human herpesvirus-6 (HHV-6, HBLV) in sarcoidosis and lymphoproliferative disorders.

Serologic studies were done to estimate the antibody prevalence against human herpesvirus 6 (HHV-6) in patients with malignant lymphomas, Sjögren's syndrome and sarcoidosis. Serologic studies showed IgG antibody titers against HHV-6 in up to 41% of patients with sarcoidosis, 50-70% with malignant lymphomas and in 36% with Sjögren's syndrome. In situ hybridization on lymph node biopsies was positive for HHV-6 genome in 1 out of 5 sarcoidosis lymph nodes.