Elevated humoral response to cytomegalovirus in HIV-infected individuals with poor CD4+ T-cell immune recovery
Identifieur interne : 002969 ( Pmc/Curation ); précédent : 002968; suivant : 002970Elevated humoral response to cytomegalovirus in HIV-infected individuals with poor CD4+ T-cell immune recovery
Auteurs : Elisabet G Mez-Mora [Espagne] ; Marta Massanella [Espagne, Canada] ; Elisabet García [Espagne] ; David Giles [Espagne] ; Marta Bernad [Espagne] ; Victor Urrea [Espagne] ; Jorge Carrillo [Espagne] ; Dan Ouchi [Espagne] ; Jordi Puig [Espagne] ; Eugenia Negredo [Espagne] ; Bonaventura Clotet [Espagne] ; Julià Blanco [Espagne] ; Cecilia Cabrera [Espagne]Source :
- PLoS ONE [ 1932-6203 ] ; 2017.
Abstract
Some HIV-infected c-ART-suppressed individuals show incomplete CD4+ T-cell recovery, abnormal T-cell activation and higher mortality. One potential source of immune activation could be coinfection with cytomegalovirus (CMV). IgG and IgM levels, immune activation, inflammation and T-cell death in c-ART-suppressed individuals with CD4+ T-cell counts >350 cells/μL (immunoconcordant, n = 133) or <350 cells/μL (immunodiscordant, n = 95) were analyzed to evaluate the effect of CMV humoral response on immune recovery. In total, 27 HIV-uninfected individuals were included as controls. In addition, the presence of CMV IgM antibodies was retrospectively analyzed in 58 immunoconcordant individuals and 66 immunodiscordant individuals. Increased CMV IgG levels were observed in individuals with poor immune reconstitution (p = 0.0002). Increased CMV IgG responses were significantly correlated with lower nadir and absolute CD4+ T-cell counts. In contrast, CMV IgG responses were positively correlated with activation (HLA-DR+) and death markers in CD4+ T-cells and activated memory CD8+ T-cells (CD45RA-CD38+). Longitudinal subanalysis revealed an increased frequency of IgM+ samples in individuals with poor CD4+ T-cell recovery, and an association was observed between retrospective IgM positivity and the current level of IgG. The magnitude of the humoral immune response to CMV is associated with nadir CD4+ T-cell counts, inflammation, immune activation and CD4+ T-cell death, thus suggesting that CMV infection may be a relevant driving force in the increased morbidity/mortality observed in HIV+ individuals with poor CD4+ T-cell recovery.
Url:
DOI: 10.1371/journal.pone.0184433
PubMed: 28934217
PubMed Central: 5608209
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T-cell immune recovery</title>
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T-cell immune recovery</title>
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<author><name sortKey="Cabrera, Cecilia" sort="Cabrera, Cecilia" uniqKey="Cabrera C" first="Cecilia" last="Cabrera">Cecilia Cabrera</name>
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<front><div type="abstract" xml:lang="en"><p>Some HIV-infected c-ART-suppressed individuals show incomplete CD4<sup>+</sup>
T-cell recovery, abnormal T-cell activation and higher mortality. One potential source of immune activation could be coinfection with cytomegalovirus (CMV). IgG and IgM levels, immune activation, inflammation and T-cell death in c-ART-suppressed individuals with CD4<sup>+</sup>
T-cell counts >350 cells/μL (immunoconcordant, n = 133) or <350 cells/μL (immunodiscordant, n = 95) were analyzed to evaluate the effect of CMV humoral response on immune recovery. In total, 27 HIV-uninfected individuals were included as controls. In addition, the presence of CMV IgM antibodies was retrospectively analyzed in 58 immunoconcordant individuals and 66 immunodiscordant individuals. Increased CMV IgG levels were observed in individuals with poor immune reconstitution (p = 0.0002). Increased CMV IgG responses were significantly correlated with lower nadir and absolute CD4<sup>+</sup>
T-cell counts. In contrast, CMV IgG responses were positively correlated with activation (HLA-DR<sup>+</sup>
) and death markers in CD4<sup>+</sup>
T-cells and activated memory CD8<sup>+</sup>
T-cells (CD45RA<sup>-</sup>
CD38<sup>+</sup>
). Longitudinal subanalysis revealed an increased frequency of IgM<sup>+</sup>
samples in individuals with poor CD4<sup>+</sup>
T-cell recovery, and an association was observed between retrospective IgM positivity and the current level of IgG. The magnitude of the humoral immune response to CMV is associated with nadir CD4<sup>+</sup>
T-cell counts, inflammation, immune activation and CD4<sup>+</sup>
T-cell death, thus suggesting that CMV infection may be a relevant driving force in the increased morbidity/mortality observed in HIV<sup>+</sup>
individuals with poor CD4<sup>+</sup>
T-cell recovery.</p>
</div>
</front>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id>
<journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id>
<journal-id journal-id-type="publisher-id">plos</journal-id>
<journal-id journal-id-type="pmc">plosone</journal-id>
<journal-title-group><journal-title>PLoS ONE</journal-title>
</journal-title-group>
<issn pub-type="epub">1932-6203</issn>
<publisher><publisher-name>Public Library of Science</publisher-name>
<publisher-loc>San Francisco, CA USA</publisher-loc>
</publisher>
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<article-meta><article-id pub-id-type="pmid">28934217</article-id>
<article-id pub-id-type="pmc">5608209</article-id>
<article-id pub-id-type="doi">10.1371/journal.pone.0184433</article-id>
<article-id pub-id-type="publisher-id">PONE-D-17-19485</article-id>
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<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Cell Biology</subject>
<subj-group><subject>Cellular Types</subject>
<subj-group><subject>Animal Cells</subject>
<subj-group><subject>Blood Cells</subject>
<subj-group><subject>White Blood Cells</subject>
<subj-group><subject>T Cells</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Cell Biology</subject>
<subj-group><subject>Cellular Types</subject>
<subj-group><subject>Animal Cells</subject>
<subj-group><subject>Immune Cells</subject>
<subj-group><subject>White Blood Cells</subject>
<subj-group><subject>T Cells</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Immunology</subject>
<subj-group><subject>Immune Cells</subject>
<subj-group><subject>White Blood Cells</subject>
<subj-group><subject>T Cells</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject>
<subj-group><subject>Immunology</subject>
<subj-group><subject>Immune Cells</subject>
<subj-group><subject>White Blood Cells</subject>
<subj-group><subject>T Cells</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and life sciences</subject>
<subj-group><subject>Cell biology</subject>
<subj-group><subject>Cellular types</subject>
<subj-group><subject>Animal cells</subject>
<subj-group><subject>Blood cells</subject>
<subj-group><subject>White blood cells</subject>
<subj-group><subject>T cells</subject>
<subj-group><subject>Cytotoxic T cells</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and life sciences</subject>
<subj-group><subject>Cell biology</subject>
<subj-group><subject>Cellular types</subject>
<subj-group><subject>Animal cells</subject>
<subj-group><subject>Immune cells</subject>
<subj-group><subject>White blood cells</subject>
<subj-group><subject>T cells</subject>
<subj-group><subject>Cytotoxic T cells</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and life sciences</subject>
<subj-group><subject>Immunology</subject>
<subj-group><subject>Immune cells</subject>
<subj-group><subject>White blood cells</subject>
<subj-group><subject>T cells</subject>
<subj-group><subject>Cytotoxic T cells</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Medicine and health sciences</subject>
<subj-group><subject>Immunology</subject>
<subj-group><subject>Immune cells</subject>
<subj-group><subject>White blood cells</subject>
<subj-group><subject>T cells</subject>
<subj-group><subject>Cytotoxic T cells</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Cell Biology</subject>
<subj-group><subject>Cell Processes</subject>
<subj-group><subject>Cell Death</subject>
<subj-group><subject>Apoptosis</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Physiology</subject>
<subj-group><subject>Immune Physiology</subject>
<subj-group><subject>Antibodies</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject>
<subj-group><subject>Physiology</subject>
<subj-group><subject>Immune Physiology</subject>
<subj-group><subject>Antibodies</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Immunology</subject>
<subj-group><subject>Immune System Proteins</subject>
<subj-group><subject>Antibodies</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject>
<subj-group><subject>Immunology</subject>
<subj-group><subject>Immune System Proteins</subject>
<subj-group><subject>Antibodies</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Biochemistry</subject>
<subj-group><subject>Proteins</subject>
<subj-group><subject>Immune System Proteins</subject>
<subj-group><subject>Antibodies</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Immunology</subject>
<subj-group><subject>Immunity</subject>
<subj-group><subject>Immune Activation</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject>
<subj-group><subject>Immunology</subject>
<subj-group><subject>Immunity</subject>
<subj-group><subject>Immune Activation</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Immunology</subject>
<subj-group><subject>Immune Response</subject>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject>
<subj-group><subject>Immunology</subject>
<subj-group><subject>Immune Response</subject>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Immunology</subject>
<subj-group><subject>Immunity</subject>
<subj-group><subject>Humoral Immunity</subject>
<subj-group><subject>Humoral Immune Response</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject>
<subj-group><subject>Immunology</subject>
<subj-group><subject>Immunity</subject>
<subj-group><subject>Humoral Immunity</subject>
<subj-group><subject>Humoral Immune Response</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and life sciences</subject>
<subj-group><subject>Organisms</subject>
<subj-group><subject>Viruses</subject>
<subj-group><subject>DNA viruses</subject>
<subj-group><subject>Herpesviruses</subject>
<subj-group><subject>Human Cytomegalovirus</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Microbiology</subject>
<subj-group><subject>Medical Microbiology</subject>
<subj-group><subject>Microbial Pathogens</subject>
<subj-group><subject>Viral Pathogens</subject>
<subj-group><subject>Herpesviruses</subject>
<subj-group><subject>Human Cytomegalovirus</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject>
<subj-group><subject>Pathology and Laboratory Medicine</subject>
<subj-group><subject>Pathogens</subject>
<subj-group><subject>Microbial Pathogens</subject>
<subj-group><subject>Viral Pathogens</subject>
<subj-group><subject>Herpesviruses</subject>
<subj-group><subject>Human Cytomegalovirus</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Organisms</subject>
<subj-group><subject>Viruses</subject>
<subj-group><subject>Viral Pathogens</subject>
<subj-group><subject>Herpesviruses</subject>
<subj-group><subject>Human Cytomegalovirus</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</article-categories>
<title-group><article-title>Elevated humoral response to cytomegalovirus in HIV-infected individuals with poor CD4<sup>+</sup>
T-cell immune recovery</article-title>
<alt-title alt-title-type="running-head">CMV IgG and IgM response and immune recovery</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Gómez-Mora</surname>
<given-names>Elisabet</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Formal analysis</role>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Visualization</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Massanella</surname>
<given-names>Marta</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Formal analysis</role>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Visualization</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff002"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>García</surname>
<given-names>Elisabet</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Giles</surname>
<given-names>David</given-names>
</name>
<role content-type="http://credit.casrai.org/">Investigation</role>
<xref ref-type="aff" rid="aff003"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bernadó</surname>
<given-names>Marta</given-names>
</name>
<role content-type="http://credit.casrai.org/">Investigation</role>
<xref ref-type="aff" rid="aff003"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Urrea</surname>
<given-names>Victor</given-names>
</name>
<role content-type="http://credit.casrai.org/">Formal analysis</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Carrillo</surname>
<given-names>Jorge</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ouchi</surname>
<given-names>Dan</given-names>
</name>
<role content-type="http://credit.casrai.org/">Formal analysis</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Puig</surname>
<given-names>Jordi</given-names>
</name>
<role content-type="http://credit.casrai.org/">Resources</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff004"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Negredo</surname>
<given-names>Eugenia</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Project administration</role>
<role content-type="http://credit.casrai.org/">Resources</role>
<role content-type="http://credit.casrai.org/">Supervision</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff004"><sup>4</sup>
</xref>
<xref ref-type="aff" rid="aff005"><sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Clotet</surname>
<given-names>Bonaventura</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Funding acquisition</role>
<role content-type="http://credit.casrai.org/">Supervision</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff004"><sup>4</sup>
</xref>
<xref ref-type="aff" rid="aff005"><sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Blanco</surname>
<given-names>Julià</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Funding acquisition</role>
<role content-type="http://credit.casrai.org/">Project administration</role>
<role content-type="http://credit.casrai.org/">Supervision</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff005"><sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author"><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-9941-6828</contrib-id>
<name><surname>Cabrera</surname>
<given-names>Cecilia</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Formal analysis</role>
<role content-type="http://credit.casrai.org/">Funding acquisition</role>
<role content-type="http://credit.casrai.org/">Project administration</role>
<role content-type="http://credit.casrai.org/">Supervision</role>
<role content-type="http://credit.casrai.org/">Visualization</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
<xref ref-type="corresp" rid="cor001">*</xref>
</contrib>
</contrib-group>
<aff id="aff001"><label>1</label>
<addr-line>IrsiCaixa AIDS Research Institute, Institut de Recerca Germans Trias i Pujol (IGTP), Hospital Universitari Germans Trias i Pujol, Universitat Autonoma de Barcelona, Badalona, Barcelona, Spain</addr-line>
</aff>
<aff id="aff002"><label>2</label>
<addr-line>Université de Montréal, Faculté de Médecine, Department of Microbiology, Infectiology and Immunology, Centre de Recherche du CHUM, Montréal, QC, Canada</addr-line>
</aff>
<aff id="aff003"><label>3</label>
<addr-line>Biokit, Lliçà d’Amunt, Barcelona, Spain</addr-line>
</aff>
<aff id="aff004"><label>4</label>
<addr-line>Fundació Lluita contra la SIDA, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain</addr-line>
</aff>
<aff id="aff005"><label>5</label>
<addr-line>Universitat de Vic-Central de Catalunya, UVIC-UCC, Vic, Spain</addr-line>
</aff>
<contrib-group><contrib contrib-type="editor"><name><surname>Spencer</surname>
<given-names>Juliet V.</given-names>
</name>
<role>Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1"><addr-line>University of San Francisco, UNITED STATES</addr-line>
</aff>
<author-notes><fn fn-type="COI-statement" id="coi001"><p><bold>Competing Interests: </bold>
EGM, MM, EG, VU, DO, JP, EN, JB and CC report no disclosures. BC has served as a consultant to and/or has received research grant support from Gilead, Janssen, MSD, ViiV and BMS. DG and MB are employees of Biokit. This does not alter our adherence to PLOS ONE policies on sharing data and materials.</p>
</fn>
<corresp id="cor001">* E-mail: <email>ccabrera@irsicaixa.es</email>
</corresp>
</author-notes>
<pub-date pub-type="epub"><day>21</day>
<month>9</month>
<year>2017</year>
</pub-date>
<pub-date pub-type="collection"><year>2017</year>
</pub-date>
<volume>12</volume>
<issue>9</issue>
<elocation-id>e0184433</elocation-id>
<history><date date-type="received"><day>21</day>
<month>5</month>
<year>2017</year>
</date>
<date date-type="accepted"><day>23</day>
<month>8</month>
<year>2017</year>
</date>
</history>
<permissions><copyright-statement>© 2017 Gómez-Mora et al</copyright-statement>
<copyright-year>2017</copyright-year>
<copyright-holder>Gómez-Mora et al</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>
, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
</license>
</permissions>
<self-uri content-type="pdf" xlink:href="pone.0184433.pdf"></self-uri>
<abstract><p>Some HIV-infected c-ART-suppressed individuals show incomplete CD4<sup>+</sup>
T-cell recovery, abnormal T-cell activation and higher mortality. One potential source of immune activation could be coinfection with cytomegalovirus (CMV). IgG and IgM levels, immune activation, inflammation and T-cell death in c-ART-suppressed individuals with CD4<sup>+</sup>
T-cell counts >350 cells/μL (immunoconcordant, n = 133) or <350 cells/μL (immunodiscordant, n = 95) were analyzed to evaluate the effect of CMV humoral response on immune recovery. In total, 27 HIV-uninfected individuals were included as controls. In addition, the presence of CMV IgM antibodies was retrospectively analyzed in 58 immunoconcordant individuals and 66 immunodiscordant individuals. Increased CMV IgG levels were observed in individuals with poor immune reconstitution (p = 0.0002). Increased CMV IgG responses were significantly correlated with lower nadir and absolute CD4<sup>+</sup>
T-cell counts. In contrast, CMV IgG responses were positively correlated with activation (HLA-DR<sup>+</sup>
) and death markers in CD4<sup>+</sup>
T-cells and activated memory CD8<sup>+</sup>
T-cells (CD45RA<sup>-</sup>
CD38<sup>+</sup>
). Longitudinal subanalysis revealed an increased frequency of IgM<sup>+</sup>
samples in individuals with poor CD4<sup>+</sup>
T-cell recovery, and an association was observed between retrospective IgM positivity and the current level of IgG. The magnitude of the humoral immune response to CMV is associated with nadir CD4<sup>+</sup>
T-cell counts, inflammation, immune activation and CD4<sup>+</sup>
T-cell death, thus suggesting that CMV infection may be a relevant driving force in the increased morbidity/mortality observed in HIV<sup>+</sup>
individuals with poor CD4<sup>+</sup>
T-cell recovery.</p>
</abstract>
<funding-group><award-group id="award001"><funding-source><institution-wrap><institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/501100003751</institution-id>
<institution>Ministerio de Sanidad, Servicios Sociales e Igualdad</institution>
</institution-wrap>
</funding-source>
<award-id>EC11-045</award-id>
<principal-award-recipient><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-9941-6828</contrib-id>
<name><surname>Cabrera</surname>
<given-names>Cecilia</given-names>
</name>
</principal-award-recipient>
</award-group>
<award-group id="award002"><funding-source><institution>Spanish AIDS network Red Temática Cooperativa de Investigación en SIDA’</institution>
</funding-source>
<award-id>RD12/0017/0002</award-id>
<principal-award-recipient><name><surname>Clotet</surname>
<given-names>Bonaventura</given-names>
</name>
</principal-award-recipient>
</award-group>
<funding-statement>This work was supported by the EC11-045 project (Ministerio de Sanidad y Política Social) and the Spanish AIDS network ‘Red Temática Cooperativa de Investigación en SIDA’ (RD12/0017/0002). Grant RD12/0017/0002 is co-funded by the Spanish Instituto de Salud Carlos III (ISCIII) and the European Fund for Regional Development (FEDER). C.C. and J.B. are supported by the ISCIII and the Health Department of the Catalan Government (Generalitat de Catalunya). DG and MB are employees of Biokit. Biokit provided support in the form of salaries for the authors [DG and MB], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.</funding-statement>
</funding-group>
<counts><fig-count count="4"></fig-count>
<table-count count="4"></table-count>
<page-count count="17"></page-count>
</counts>
<custom-meta-group><custom-meta id="data-availability"><meta-name>Data Availability</meta-name>
<meta-value>All relevant data are within the paper and its Supporting Information files.</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
<notes><title>Data Availability</title>
<p>All relevant data are within the paper and its Supporting Information files.</p>
</notes>
</front>
</pmc>
</record>
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