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Toxoplasmosis-associated IRIS involving the CNS: a case report with longitudinal analysis of T cell subsets

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Resumo:Background: 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. Case presentation: 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. Conclusion: 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.
Autores principais:Silva, Rita Catarina Assunção Ribeiro
Outros Autores:Nóbrega, Cláudia; Reiriz, Eugénia; Almeida, Soraia; Castro, Rui Manuel Rosário Sarmento; Neves, Margarida Correia; Horta, Ana Maria Lacerda Morgado Fernandes Carvalho Aboim
Assunto:Human immunodeficiency virus Immune reconstitution inflammatory syndrome Toxoplasmosis T cell subsets Regulatory T cells
Ano:2017
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso aberto
Instituição associada:Universidade do Minho
Idioma:inglês
Origem:RepositóriUM - Universidade do Minho
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author Silva, Rita Catarina Assunção Ribeiro
author2 Nóbrega, Cláudia
Reiriz, Eugénia
Almeida, Soraia
Castro, Rui Manuel Rosário Sarmento
Neves, Margarida Correia
Horta, Ana Maria Lacerda Morgado Fernandes Carvalho Aboim
author2_role author
author
author
author
author
author
author_facet Silva, Rita Catarina Assunção Ribeiro
Nóbrega, Cláudia
Reiriz, Eugénia
Almeida, Soraia
Castro, Rui Manuel Rosário Sarmento
Neves, Margarida Correia
Horta, Ana Maria Lacerda Morgado Fernandes Carvalho Aboim
author_role author
contributor_name_str_mv Universidade do Minho
country_str PT
creators_json_txt [{\"Person.name\":\"Silva, Rita Catarina Assunção Ribeiro\"},{\"Person.name\":\"Nóbrega, Cláudia\"},{\"Person.name\":\"Reiriz, Eugénia\"},{\"Person.name\":\"Almeida, Soraia\"},{\"Person.name\":\"Castro, Rui Manuel Rosário Sarmento\"},{\"Person.name\":\"Neves, Margarida Correia\"},{\"Person.name\":\"Horta, Ana Maria Lacerda Morgado Fernandes Carvalho Aboim\"}]
datacite.contributors.contributor.contributorName.fl_str_mv Universidade do Minho
datacite.creators.creator.creatorName.fl_str_mv Silva, Rita Catarina Assunção Ribeiro
Nóbrega, Cláudia
Reiriz, Eugénia
Almeida, Soraia
Castro, Rui Manuel Rosário Sarmento
Neves, Margarida Correia
Horta, Ana Maria Lacerda Morgado Fernandes Carvalho Aboim
datacite.date.Accepted.fl_str_mv 2017-01-01T00:00:00Z
datacite.date.available.fl_str_mv 2017-12-21T16:02:20Z
datacite.date.embargoed.fl_str_mv 2017-12-21T16:02:20Z
datacite.rights.fl_str_mv http://purl.org/coar/access_right/c_abf2
datacite.subjects.subject.fl_str_mv Human immunodeficiency virus
Immune reconstitution inflammatory syndrome
Toxoplasmosis
T cell subsets
Regulatory T cells
datacite.titles.title.fl_str_mv Toxoplasmosis-associated IRIS involving the CNS: a case report with longitudinal analysis of T cell subsets
dc.contributor.none.fl_str_mv Universidade do Minho
dc.creator.none.fl_str_mv Silva, Rita Catarina Assunção Ribeiro
Nóbrega, Cláudia
Reiriz, Eugénia
Almeida, Soraia
Castro, Rui Manuel Rosário Sarmento
Neves, Margarida Correia
Horta, Ana Maria Lacerda Morgado Fernandes Carvalho Aboim
dc.date.Accepted.fl_str_mv 2017-01-01T00:00:00Z
dc.date.available.fl_str_mv 2017-12-21T16:02:20Z
dc.date.embargoed.fl_str_mv 2017-12-21T16:02:20Z
dc.format.none.fl_str_mv application/pdf
dc.identifier.none.fl_str_mv https://hdl.handle.net/1822/48519
dc.language.none.fl_str_mv eng
dc.publisher.none.fl_str_mv BioMed Central (BMC)
dc.rights.none.fl_str_mv http://purl.org/coar/access_right/c_abf2
dc.subject.none.fl_str_mv Human immunodeficiency virus
Immune reconstitution inflammatory syndrome
Toxoplasmosis
T cell subsets
Regulatory T cells
dc.title.fl_str_mv Toxoplasmosis-associated IRIS involving the CNS: a case report with longitudinal analysis of T cell subsets
dc.type.none.fl_str_mv http://purl.org/coar/resource_type/c_6501
description Background: 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. Case presentation: 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. Conclusion: 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.
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institution Universidade do Minho
instname_str Universidade do Minho
language eng
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oai_identifier_str oai:repositorium.uminho.pt:1822/48519
organization_str_mv urn:organizationAcronym:repositorium
person_str_mv Silva, Rita Catarina Assunção Ribeiro
Nóbrega, Cláudia
Reiriz, Eugénia
Almeida, Soraia
Castro, Rui Manuel Rosário Sarmento
Neves, Margarida Correia
Horta, Ana Maria Lacerda Morgado Fernandes Carvalho Aboim
publishDate 2017
publisher.none.fl_str_mv BioMed Central (BMC)
reponame_str RepositóriUM - Universidade do Minho
repository_id_str urn:repositoryAcronym:rum
service_str_mv urn:repositoryAcronym:rum
spelling engBioMed Central (BMC)porBackground: 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. Case presentation: 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. Conclusion: 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.application/pdfporToxoplasmosis-associated IRIS involving the CNS: a case report with longitudinal analysis of T cell subsetsSilva, Rita Catarina Assunção RibeiroNóbrega, CláudiaReiriz, EugéniaAlmeida, SoraiaCastro, Rui Manuel Rosário SarmentoNeves, Margarida CorreiaHorta, Ana Maria Lacerda Morgado Fernandes Carvalho AboimHostingInstitutionOrganizationalUniversidade do Minhoe-mailmailto:repositorium@usdb.uminho.ptrepositorium@usdb.uminho.ptISSNIsPartOf1471-2334DOIIsPartOf10.1186/s12879-016-2159-x2017-12-21T16:02:20Z20172017-12-15T16:59:20Z2017-01-01T00:00:00ZHandlehttps://hdl.handle.net/1822/48519http://purl.org/coar/access_right/c_abf2open accessHuman immunodeficiency virusImmune reconstitution inflammatory syndromeToxoplasmosisT cell subsetsRegulatory T cells2022502 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://prod-dspace.uminho.pt/bitstreams/17a43816-c93a-45ab-909e-0fde709ab9ea/download
spellingShingle Toxoplasmosis-associated IRIS involving the CNS: a case report with longitudinal analysis of T cell subsets
Silva, Rita Catarina Assunção Ribeiro
Human immunodeficiency virus
Immune reconstitution inflammatory syndrome
Toxoplasmosis
T cell subsets
Regulatory T cells
status SINGLETON
subject.fl_str_mv Human immunodeficiency virus
Immune reconstitution inflammatory syndrome
Toxoplasmosis
T cell subsets
Regulatory T cells
title Toxoplasmosis-associated IRIS involving the CNS: a case report with longitudinal analysis of T cell subsets
title_full Toxoplasmosis-associated IRIS involving the CNS: a case report with longitudinal analysis of T cell subsets
title_fullStr Toxoplasmosis-associated IRIS involving the CNS: a case report with longitudinal analysis of T cell subsets
title_full_unstemmed Toxoplasmosis-associated IRIS involving the CNS: a case report with longitudinal analysis of T cell subsets
title_short Toxoplasmosis-associated IRIS involving the CNS: a case report with longitudinal analysis of T cell subsets
title_sort Toxoplasmosis-associated IRIS involving the CNS: a case report with longitudinal analysis of T cell subsets
topic Human immunodeficiency virus
Immune reconstitution inflammatory syndrome
Toxoplasmosis
T cell subsets
Regulatory T cells
topic_facet Human immunodeficiency virus
Immune reconstitution inflammatory syndrome
Toxoplasmosis
T cell subsets
Regulatory T cells
url https://hdl.handle.net/1822/48519
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