title: Toxoplasmosis-associated IRIS involving the CNS: a case report with longitudinal analysis of T cell subsets.
abstract: HIV-infected patients may present an unforeseen clinical worsening after initiating antiretroviral therapy known as immune reconstitution inflammatory syndrome (IRIS). This syndrome is characterized by a heightened inflammatory response toward infectious or non-infectious triggers, and it may affect different organs. Diagnosis of IRIS involving the central nervous system (CNS-IRIS) is challenging due to heterogeneous manifestations, absence of biomarkers to identify this condition, risk of long-term sequelae and high mortality. Hence, a deeper knowledge of CNS-IRIS pathogenesis is needed.
  
  
  
  A 37-year-old man was diagnosed with AIDS and cerebral toxoplasmosis. Anti-toxoplasma treatment was initiated immediately, followed by active antiretroviral therapy (HAART) 1 month later. At 2 months of HAART, he presented with progressive hyposensitivity of the right lower limb associated with brain and dorsal spinal cord lesions, compatible with paradoxical toxoplasmosis-associated CNS-IRIS, a condition with very few reported cases. A stereotactic biopsy was planned but was postponed based on its inherent risks. Patient showed clinical improvement with no requirement of corticosteroid therapy. Routine laboratorial analysis was complemented with longitudinal evaluation of blood T cell subsets at 0, 1, 2, 3 and 6 months upon HAART initiation. A control group composed by 9 HIV-infected patients from the same hospital but with no IRIS was analysed for comparison. The CNS-IRIS patient showed lower percentage of memory CD4+T cells and higher percentage of activated CD4+T cells at HAART initiation. The percentage of memory CD4+T cells drastically increased at 1 month after HAART initiation and became higher in comparison to the control group until clinical recovery onset; the percentage of memory CD8+T cells was consistently lower throughout follow-up. Interestingly, the percentage of regulatory T cells (Treg) on the CNS-IRIS patient reached a minimum around 1 month before symptoms onset.
  
  
  
  Although both stereotactic biopsies and steroid therapy might be of use in CNS-IRIS cases and should be considered for these patients, they might be unnecessary to achieve clinical improvement as shown in this case. Immunological characterization of more CNS-IRIS cases is essential to shed some light on the pathogenesis of this condition.
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal.|ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Rita
authors.initials: R
authors.lastname: Rb-Silva
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal.|ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Claudia
authors.initials: C
authors.lastname: Nobrega
authors.affiliation: Department of Infectious Diseases of Centro Hospitalar do Porto, Hospital Joaquim Urbano Unit, Porto, Portugal.
authors.forename: Eugénia
authors.initials: E
authors.lastname: Reiriz
authors.affiliation: Department of Infectious Diseases of Centro Hospitalar do Porto, Hospital Joaquim Urbano Unit, Porto, Portugal.
authors.forename: Soraia
authors.initials: S
authors.lastname: Almeida
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal.|ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal.|Department of Infectious Diseases of Centro Hospitalar do Porto, Hospital Joaquim Urbano Unit, Porto, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Sarmento-Castro
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal. mcorreianeves@med.uminho.pt.|ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal. mcorreianeves@med.uminho.pt.
authors.forename: Margarida
authors.initials: M
authors.lastname: Correia-Neves
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal.|ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal.|Department of Infectious Diseases of Centro Hospitalar do Porto, Hospital Joaquim Urbano Unit, Porto, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Horta
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects; D000981:Antiprotozoal Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D001921:Brain / Q000000981:diagnostic imaging; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002493:Central Nervous System Diseases / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000276:immunology*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D013116:Spinal Cord / Q000000981:diagnostic imaging; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014057:Tomography, X-Ray Computed; D016781:Toxoplasmosis, Cerebral / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000276:immunology*
chemical_list: D019380:Anti-HIV Agents; D000981:Antiprotozoal Agents
keywords: Human immunodeficiency virus; Immune reconstitution inflammatory syndrome; Regulatory T cells; T cell subsets; Toxoplasmosis