Guillaume Martin-Blondel1, Jan Bauer, Victor Cuvinciuc, Emmanuelle Uro-Coste, Alexa Debard, Patrice Massip, Marie-Bernadette Delisle, Hans Lassmann, Bruno Marchou, Lennart T Mars, Roland S Liblau. 1. From the Departments of Infectious and Tropical Diseases (G.M.-B., A.D., P.M., B.M.), Neuroradiology (V.C.), and Pathology (E.U.-C., M.-B.D.), Toulouse University Hospital; INSERM U1043-CNRS UMR 5282 (G.M.-B., L.T.M., R.S.L.), Centre de Physiopathologie Toulouse-Purpan; Université Toulouse III (G.M.-B., V.C., E.U.-C., P.M., M.-B.D., B.M., L.T.M., R.S.L.), France; Center for Brain Research (J.B., H.L.), Medical University of Vienna, Austria; INSERM (E.U.-C., M.-B.D.), CRCT U1087, Toulouse; and CNRS, LCC (B.M.), Université de Toulouse, France.
Abstract
OBJECTIVE: To determine the pathophysiologic features of progressive multifocal leukoencephalopathy (PML) associated with immune reconstitution inflammatory syndrome (PML-IRIS) in HIV-infected patients. METHODS: In a cross-sectional study, we retrospectively analyzed 11 HIV-infected patients with a firm diagnosis of PML-IRIS. Brain biopsies were collected from 5 patients and their histopathologic features were compared to those of 4 HIV-infected patients with classic PML. RESULTS: PML-IRIS developed soon after initiation of antiretroviral therapy in late-presenting HIV-infected patients. The lesions from the 5 biopsied PML-IRIS patients were characterized by a reduction in the density of JC virus (JCV)-infected cells when compared to the 4 patients with PML (11.1 ± 3.2/mm² vs 51.2 ± 4.3/mm², p = 0.01). Comparing the 5 patients with PML-IRIS vs the 4 patients with PML, this correlated with an increased accumulation of CD8+ T cells (818.2 ± 192.8/mm² vs 52.5 ± 10.6/mm², p = 0.01), CD20+ B cells (33.4 ± 13.5/mm² vs 0.5 ± 0.5/mm², p = 0.01), and CD138+ plasma cells (177 ± 84.1/mm² vs 0.25 ± 0.25/mm², p = 0.01), while the number of CD68+ macrophages/microglia did not differ. The ratio between CD8+ T cells and JCV-infected cells was 70 times higher in the 5 patients with PML-IRIS. These findings indicate a clear relationship between an enhanced recruitment of CD8+ T cells and the associated control of the JCV infection. CONCLUSIONS: Our data provide in situ evidence that PML-IRIS brain lesions are enriched in cytotoxic CD8+ T cells that engage JCV-infected oligodendrocytes. This leads to a better control of JCV dissemination, but at the cost of oligodendrocyte cell death and demyelination.
OBJECTIVE: To determine the pathophysiologic features of progressive multifocal leukoencephalopathy (PML) associated with immune reconstitution inflammatory syndrome (PML-IRIS) in HIV-infectedpatients. METHODS: In a cross-sectional study, we retrospectively analyzed 11 HIV-infectedpatients with a firm diagnosis of PML-IRIS. Brain biopsies were collected from 5 patients and their histopathologic features were compared to those of 4 HIV-infectedpatients with classic PML. RESULTS: PML-IRIS developed soon after initiation of antiretroviral therapy in late-presenting HIV-infectedpatients. The lesions from the 5 biopsied PML-IRIS patients were characterized by a reduction in the density of JC virus (JCV)-infected cells when compared to the 4 patients with PML (11.1 ± 3.2/mm² vs 51.2 ± 4.3/mm², p = 0.01). Comparing the 5 patients with PML-IRIS vs the 4 patients with PML, this correlated with an increased accumulation of CD8+ T cells (818.2 ± 192.8/mm² vs 52.5 ± 10.6/mm², p = 0.01), CD20+ B cells (33.4 ± 13.5/mm² vs 0.5 ± 0.5/mm², p = 0.01), and CD138+ plasma cells (177 ± 84.1/mm² vs 0.25 ± 0.25/mm², p = 0.01), while the number of CD68+ macrophages/microglia did not differ. The ratio between CD8+ T cells and JCV-infected cells was 70 times higher in the 5 patients with PML-IRIS. These findings indicate a clear relationship between an enhanced recruitment of CD8+ T cells and the associated control of the JCV infection. CONCLUSIONS: Our data provide in situ evidence that PML-IRIS brain lesions are enriched in cytotoxic CD8+ T cells that engage JCV-infected oligodendrocytes. This leads to a better control of JCV dissemination, but at the cost of oligodendrocyte cell death and demyelination.
Authors: Aabha Oza; Michael P Rettig; Phil Powell; Kathryn O'Brien; David B Clifford; Julie Ritchey; Leah Gehrs; Julia Hollaway; Eugene Major; Todd A Fehniger; Christopher A Miller; Patrick Soon-Shiong; Amy Rock; John F DiPersio Journal: Blood Adv Date: 2020-06-09
Authors: Guillaume Martin-Blondel; David Brassat; Jan Bauer; Hans Lassmann; Roland S Liblau Journal: Nat Rev Neurol Date: 2016-01-18 Impact factor: 42.937