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

2017-01-13Journal article Open access
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dc.contributor.authorRb-Silva, R.
dc.contributor.authorNobrega, C.
dc.contributor.authorReiriz, E.
dc.contributor.authorAlmeida, S.
dc.contributor.authorSarmento-Castro, R.
dc.contributor.authorCorreia-Neves, M.
dc.contributor.authorHorta, A.
dc.date.accessioned2017-08-31T12:25:35Z
dc.date.available2017-08-31T12:25:35Z
dc.date.issued2017-01-13
dc.description.abstractBACKGROUND: 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.pt_PT
dc.description.sponsorshipThis work was funded by the Portuguese Foundation for Science and Technology (FCT; PIC/IC/83313/2007) and co-financed by the Portuguese North Regional Operational Program (ON.2 - O Novo Norte) under the National Strategic Reference Framework (QREN) through the European Regional Development Fund (FEDER). A FCT fellowship was attributed to RRS (PD/BD/106047/2015; Inter-University Doctoral Program in Ageing and Chronic Disease) and to CN [SFRH/BPD/65380/2009; Programa Operacional Potencial Humano (POPH) through the Fundo Social Europeu (FSE)].pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationBMC Infect Dis. 2017 Jan 13;17(1):66pt_PT
dc.identifier.doi10.1186/s12879-016-2159-xpt_PT
dc.identifier.issn1471-2334
dc.identifier.urihttp://hdl.handle.net/10400.16/2174
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherBioMed Centralpt_PT
dc.relationRECONSTITUTION AND HOMEOSTHASIS OF THE IMMUNE SYSTEM FOLLOWING HIV-INFECTION
dc.relation.publisherversionhttps://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-016-2159-xpt_PT
dc.subjectHuman immunodeficiency viruspt_PT
dc.subjectImmune reconstitution inflammatory syndromept_PT
dc.subjectRegulatory T cellspt_PT
dc.subjectT cell subsetspt_PT
dc.subjectToxoplasmosispt_PT
dc.titleToxoplasmosis-associated IRIS involving the CNS: a case report with longitudinal analysis of T cell subsetspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleRECONSTITUTION AND HOMEOSTHASIS OF THE IMMUNE SYSTEM FOLLOWING HIV-INFECTION
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876-PPCDTI/PIC%2FIC%2F83313%2F2007/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBPD%2F65380%2F2009/PT
oaire.citation.conferencePlaceEnglandpt_PT
oaire.citation.issue1pt_PT
oaire.citation.startPage66pt_PT
oaire.citation.titleBMC Infectious Diseasespt_PT
oaire.citation.volume17pt_PT
oaire.fundingStream5876-PPCDTI
oaire.fundingStreamSFRH
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublicatione71ee952-c9eb-4e63-8e68-57f34d8f6ab4
relation.isProjectOfPublicationd5b62ec9-6025-4009-a626-17f6bc20a81a
relation.isProjectOfPublication.latestForDiscoveryd5b62ec9-6025-4009-a626-17f6bc20a81a

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