The Kynurenine Pathway of Tryptophan Catabolism and AIDS-associated Kaposi's Sarcoma in Africa
Identifieur interne : 001942 ( Pmc/Corpus ); précédent : 001941; suivant : 001943The Kynurenine Pathway of Tryptophan Catabolism and AIDS-associated Kaposi's Sarcoma in Africa
Auteurs : Helen Byakwaga ; Peter W. Hunt ; Miriam Laker-Oketta ; David V. Glidden ; Yong Huang ; Bosco M. Bwana ; A. Rain Mocello ; John Bennett ; Victoria Walusansa ; Sheila C. Dollard ; David R. Bangsberg ; Edward K. Mbidde ; Jeffrey N. MartinSource :
- Journal of acquired immune deficiency syndromes (1999) [ 1525-4135 ] ; 2015.
Abstract
Other than Kaposi's sarcoma (KS)-associated herpesvirus and CD4+ T cell lymphopenia, the mechanisms responsible for KS in the context of HIV are poorly understood. One recently explored pathway of HIV pathogenesis involves induction of the enzyme indoleamine 2,3 dioxygenase-1 (IDO), which catabolizes tryptophan into kynurenine and several other immunologically active metabolites that suppress T cell proliferation. We investigated the role of IDO in the development of KS in HIV disease.
In a case-control study among untreated HIV-infected Ugandans, cases were adults with KS and controls were without KS. IDO activity was assessed by the ratio of plasma kynurenine to tryptophan levels (KT ratio), measured by liquid chromatography tandem mass spectrometry.
We studied 631 HIV-infected subjects: 222 KS cases and 409 controls. Non-KS controls had a higher median plasma KT ratio (130, IQR: 90 to190 nM/μM) than cases (110, IQR: 90 to 150 nM/μM) (p = 0.004). After adjustment for age, sex, CD4 count and plasma HIV RNA level, subjects with the highest (fourth quartile) plasma KT ratios had a 59% reduction (95% CI: 27% to 77%) in the odds of KS compared to those with the lowest (first quartile) levels. KS was also independently associated with lower CD4+ count, higher plasma HIV RNA, and men.
Among HIV-infected individuals, greater activity of the kynurenine pathway of tryptophan catabolism, as evidenced by higher levels of plasma KT ratio, was associated with lower occurrence of KS. Some consequences of immune activation in HIV infection might actually suppress certain cancers.
Url:
DOI: 10.1097/QAI.0000000000000747
PubMed: 26181812
PubMed Central: 4607630
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Hunt</name><affiliation><nlm:aff id="A2"> University of California, San Francisco</nlm:aff></affiliation></author><author><name sortKey="Laker Oketta, Miriam" sort="Laker Oketta, Miriam" uniqKey="Laker Oketta M" first="Miriam" last="Laker-Oketta">Miriam Laker-Oketta</name><affiliation><nlm:aff id="A2"> University of California, San Francisco</nlm:aff></affiliation><affiliation><nlm:aff id="A3"> Infectious Diseases Institute, Kampala, Uganda</nlm:aff></affiliation></author><author><name sortKey="Glidden, David V" sort="Glidden, David V" uniqKey="Glidden D" first="David V." last="Glidden">David V. Glidden</name><affiliation><nlm:aff id="A2"> University of California, San Francisco</nlm:aff></affiliation></author><author><name sortKey="Huang, Yong" sort="Huang, Yong" uniqKey="Huang Y" first="Yong" last="Huang">Yong Huang</name><affiliation><nlm:aff id="A2"> University of California, San Francisco</nlm:aff></affiliation></author><author><name sortKey="Bwana, Bosco M" sort="Bwana, Bosco M" uniqKey="Bwana B" first="Bosco M" last="Bwana">Bosco M. Bwana</name><affiliation><nlm:aff id="A1"> Mbarara University of Science and Technology, Mbarara, Uganda</nlm:aff></affiliation></author><author><name sortKey="Mocello, A Rain" sort="Mocello, A Rain" uniqKey="Mocello A" first="A. Rain" last="Mocello">A. Rain Mocello</name><affiliation><nlm:aff id="A2"> University of California, San Francisco</nlm:aff></affiliation></author><author><name sortKey="Bennett, John" sort="Bennett, John" uniqKey="Bennett J" first="John" last="Bennett">John Bennett</name><affiliation><nlm:aff id="A2"> University of California, San Francisco</nlm:aff></affiliation></author><author><name sortKey="Walusansa, Victoria" sort="Walusansa, Victoria" uniqKey="Walusansa V" first="Victoria" last="Walusansa">Victoria Walusansa</name><affiliation><nlm:aff id="A4"> Uganda Cancer Institute, Kampala, Uganda</nlm:aff></affiliation></author><author><name sortKey="Dollard, Sheila C" sort="Dollard, Sheila C" uniqKey="Dollard S" first="Sheila C." last="Dollard">Sheila C. Dollard</name><affiliation><nlm:aff id="A5"> Centers for Disease Control and Prevention, Atlanta, Georgia</nlm:aff></affiliation></author><author><name sortKey="Bangsberg, David R" sort="Bangsberg, David R" uniqKey="Bangsberg D" first="David R." last="Bangsberg">David R. Bangsberg</name><affiliation><nlm:aff id="A6"> Massachusetts General Hospital, Center for Global Health, Harvard Medical School, Boston, Massachusetts</nlm:aff></affiliation></author><author><name sortKey="Mbidde, Edward K" sort="Mbidde, Edward K" uniqKey="Mbidde E" first="Edward K." last="Mbidde">Edward K. Mbidde</name><affiliation><nlm:aff id="A3"> Infectious Diseases Institute, Kampala, Uganda</nlm:aff></affiliation><affiliation><nlm:aff id="A7"> Uganda Virus Research Institute, Entebbe, Uganda</nlm:aff></affiliation></author><author><name sortKey="Martin, Jeffrey N" sort="Martin, Jeffrey N" uniqKey="Martin J" first="Jeffrey N." last="Martin">Jeffrey N. Martin</name><affiliation><nlm:aff id="A2"> University of California, San Francisco</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26181812</idno><idno type="pmc">4607630</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4607630</idno><idno type="RBID">PMC:4607630</idno><idno type="doi">10.1097/QAI.0000000000000747</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">001942</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001942</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The Kynurenine Pathway of Tryptophan Catabolism and AIDS-associated Kaposi's Sarcoma in Africa</title><author><name sortKey="Byakwaga, Helen" sort="Byakwaga, Helen" uniqKey="Byakwaga H" first="Helen" last="Byakwaga">Helen Byakwaga</name><affiliation><nlm:aff id="A1"> Mbarara University of Science and Technology, Mbarara, Uganda</nlm:aff></affiliation><affiliation><nlm:aff id="A2"> University of California, San Francisco</nlm:aff></affiliation></author><author><name sortKey="Hunt, Peter W" sort="Hunt, Peter W" uniqKey="Hunt P" first="Peter W." last="Hunt">Peter W. Hunt</name><affiliation><nlm:aff id="A2"> University of California, San Francisco</nlm:aff></affiliation></author><author><name sortKey="Laker Oketta, Miriam" sort="Laker Oketta, Miriam" uniqKey="Laker Oketta M" first="Miriam" last="Laker-Oketta">Miriam Laker-Oketta</name><affiliation><nlm:aff id="A2"> University of California, San Francisco</nlm:aff></affiliation><affiliation><nlm:aff id="A3"> Infectious Diseases Institute, Kampala, Uganda</nlm:aff></affiliation></author><author><name sortKey="Glidden, David V" sort="Glidden, David V" uniqKey="Glidden D" first="David V." last="Glidden">David V. Glidden</name><affiliation><nlm:aff id="A2"> University of California, San Francisco</nlm:aff></affiliation></author><author><name sortKey="Huang, Yong" sort="Huang, Yong" uniqKey="Huang Y" first="Yong" last="Huang">Yong Huang</name><affiliation><nlm:aff id="A2"> University of California, San Francisco</nlm:aff></affiliation></author><author><name sortKey="Bwana, Bosco M" sort="Bwana, Bosco M" uniqKey="Bwana B" first="Bosco M" last="Bwana">Bosco M. Bwana</name><affiliation><nlm:aff id="A1"> Mbarara University of Science and Technology, Mbarara, Uganda</nlm:aff></affiliation></author><author><name sortKey="Mocello, A Rain" sort="Mocello, A Rain" uniqKey="Mocello A" first="A. Rain" last="Mocello">A. Rain Mocello</name><affiliation><nlm:aff id="A2"> University of California, San Francisco</nlm:aff></affiliation></author><author><name sortKey="Bennett, John" sort="Bennett, John" uniqKey="Bennett J" first="John" last="Bennett">John Bennett</name><affiliation><nlm:aff id="A2"> University of California, San Francisco</nlm:aff></affiliation></author><author><name sortKey="Walusansa, Victoria" sort="Walusansa, Victoria" uniqKey="Walusansa V" first="Victoria" last="Walusansa">Victoria Walusansa</name><affiliation><nlm:aff id="A4"> Uganda Cancer Institute, Kampala, Uganda</nlm:aff></affiliation></author><author><name sortKey="Dollard, Sheila C" sort="Dollard, Sheila C" uniqKey="Dollard S" first="Sheila C." last="Dollard">Sheila C. Dollard</name><affiliation><nlm:aff id="A5"> Centers for Disease Control and Prevention, Atlanta, Georgia</nlm:aff></affiliation></author><author><name sortKey="Bangsberg, David R" sort="Bangsberg, David R" uniqKey="Bangsberg D" first="David R." last="Bangsberg">David R. Bangsberg</name><affiliation><nlm:aff id="A6"> Massachusetts General Hospital, Center for Global Health, Harvard Medical School, Boston, Massachusetts</nlm:aff></affiliation></author><author><name sortKey="Mbidde, Edward K" sort="Mbidde, Edward K" uniqKey="Mbidde E" first="Edward K." last="Mbidde">Edward K. Mbidde</name><affiliation><nlm:aff id="A3"> Infectious Diseases Institute, Kampala, Uganda</nlm:aff></affiliation><affiliation><nlm:aff id="A7"> Uganda Virus Research Institute, Entebbe, Uganda</nlm:aff></affiliation></author><author><name sortKey="Martin, Jeffrey N" sort="Martin, Jeffrey N" uniqKey="Martin J" first="Jeffrey N." last="Martin">Jeffrey N. Martin</name><affiliation><nlm:aff id="A2"> University of California, San Francisco</nlm:aff></affiliation></author></analytic><series><title level="j">Journal of acquired immune deficiency syndromes (1999)</title><idno type="ISSN">1525-4135</idno><idno type="eISSN">1944-7884</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background</title><p id="P1">Other than Kaposi's sarcoma (KS)-associated herpesvirus and CD4+ T cell lymphopenia, the mechanisms responsible for KS in the context of HIV are poorly understood. One recently explored pathway of HIV pathogenesis involves induction of the enzyme indoleamine 2,3 dioxygenase-1 (IDO), which catabolizes tryptophan into kynurenine and several other immunologically active metabolites that suppress T cell proliferation. We investigated the role of IDO in the development of KS in HIV disease.</p></sec><sec id="S2"><title>Methods</title><p id="P2">In a case-control study among untreated HIV-infected Ugandans, cases were adults with KS and controls were without KS. IDO activity was assessed by the ratio of plasma kynurenine to tryptophan levels (KT ratio), measured by liquid chromatography tandem mass spectrometry.</p></sec><sec id="S3"><title>Results</title><p id="P3">We studied 631 HIV-infected subjects: 222 KS cases and 409 controls. Non-KS controls had a higher median plasma KT ratio (130, IQR: 90 to190 nM/μM) than cases (110, IQR: 90 to 150 nM/μM) (p = 0.004). After adjustment for age, sex, CD4 count and plasma HIV RNA level, subjects with the highest (fourth quartile) plasma KT ratios had a 59% reduction (95% CI: 27% to 77%) in the odds of KS compared to those with the lowest (first quartile) levels. KS was also independently associated with lower CD4+ count, higher plasma HIV RNA, and men.</p></sec><sec id="S4"><title>Conclusions</title><p id="P4">Among HIV-infected individuals, greater activity of the kynurenine pathway of tryptophan catabolism, as evidenced by higher levels of plasma KT ratio, was associated with lower occurrence of KS. Some consequences of immune activation in HIV infection might actually suppress certain cancers.</p></sec></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">100892005</journal-id><journal-id journal-id-type="pubmed-jr-id">21821</journal-id><journal-id journal-id-type="nlm-ta">J Acquir Immune Defic Syndr</journal-id><journal-id journal-id-type="iso-abbrev">J. Acquir. Immune Defic. Syndr.</journal-id><journal-title-group><journal-title>Journal of acquired immune deficiency syndromes (1999)</journal-title></journal-title-group><issn pub-type="ppub">1525-4135</issn><issn pub-type="epub">1944-7884</issn></journal-meta><article-meta><article-id pub-id-type="pmid">26181812</article-id><article-id pub-id-type="pmc">4607630</article-id><article-id pub-id-type="doi">10.1097/QAI.0000000000000747</article-id><article-id pub-id-type="manuscript">NIHMS703194</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>The Kynurenine Pathway of Tryptophan Catabolism and AIDS-associated Kaposi's Sarcoma in Africa</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Byakwaga</surname><given-names>Helen</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Hunt</surname><given-names>Peter W.</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Laker-Oketta</surname><given-names>Miriam</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Glidden</surname><given-names>David V.</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Huang</surname><given-names>Yong</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Bwana</surname><given-names>Bosco M</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Mocello</surname><given-names>A. Rain</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Bennett</surname><given-names>John</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Walusansa</surname><given-names>Victoria</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Dollard</surname><given-names>Sheila C.</given-names></name><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Bangsberg</surname><given-names>David R.</given-names></name><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Mbidde</surname><given-names>Edward K.</given-names></name><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Martin</surname><given-names>Jeffrey N.</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib></contrib-group><aff id="A1"><label>1</label> Mbarara University of Science and Technology, Mbarara, Uganda</aff><aff id="A2"><label>2</label> University of California, San Francisco</aff><aff id="A3"><label>3</label> Infectious Diseases Institute, Kampala, Uganda</aff><aff id="A4"><label>4</label> Uganda Cancer Institute, Kampala, Uganda</aff><aff id="A5"><label>5</label> Centers for Disease Control and Prevention, Atlanta, Georgia</aff><aff id="A6"><label>6</label> Massachusetts General Hospital, Center for Global Health, Harvard Medical School, Boston, Massachusetts</aff><aff id="A7"><label>7</label> Uganda Virus Research Institute, Entebbe, Uganda</aff><author-notes><corresp id="CR1"><bold>Corresponding Author:</bold> Helen Byakwaga, PhD Mbarara University of Science and Technology P.O. Box 1397 Mbarara, Uganda <email>hbyakwaga@gmail.com</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>8</day><month>7</month><year>2015</year></pub-date><pub-date pub-type="ppub"><day>1</day><month>11</month><year>2015</year></pub-date><pub-date pub-type="pmc-release"><day>01</day><month>11</month><year>2016</year></pub-date><volume>70</volume><issue>3</issue><fpage>296</fpage><lpage>303</lpage><pmc-comment>elocation-id from pubmed: 10.1097/QAI.0000000000000747</pmc-comment>
<abstract><sec id="S1"><title>Background</title><p id="P1">Other than Kaposi's sarcoma (KS)-associated herpesvirus and CD4+ T cell lymphopenia, the mechanisms responsible for KS in the context of HIV are poorly understood. One recently explored pathway of HIV pathogenesis involves induction of the enzyme indoleamine 2,3 dioxygenase-1 (IDO), which catabolizes tryptophan into kynurenine and several other immunologically active metabolites that suppress T cell proliferation. We investigated the role of IDO in the development of KS in HIV disease.</p></sec><sec id="S2"><title>Methods</title><p id="P2">In a case-control study among untreated HIV-infected Ugandans, cases were adults with KS and controls were without KS. IDO activity was assessed by the ratio of plasma kynurenine to tryptophan levels (KT ratio), measured by liquid chromatography tandem mass spectrometry.</p></sec><sec id="S3"><title>Results</title><p id="P3">We studied 631 HIV-infected subjects: 222 KS cases and 409 controls. Non-KS controls had a higher median plasma KT ratio (130, IQR: 90 to190 nM/μM) than cases (110, IQR: 90 to 150 nM/μM) (p = 0.004). After adjustment for age, sex, CD4 count and plasma HIV RNA level, subjects with the highest (fourth quartile) plasma KT ratios had a 59% reduction (95% CI: 27% to 77%) in the odds of KS compared to those with the lowest (first quartile) levels. KS was also independently associated with lower CD4+ count, higher plasma HIV RNA, and men.</p></sec><sec id="S4"><title>Conclusions</title><p id="P4">Among HIV-infected individuals, greater activity of the kynurenine pathway of tryptophan catabolism, as evidenced by higher levels of plasma KT ratio, was associated with lower occurrence of KS. Some consequences of immune activation in HIV infection might actually suppress certain cancers.</p></sec></abstract><kwd-group><kwd>tryptophan</kwd><kwd>kynurenine</kwd><kwd>indoleamine 2,3-dioxygenase-1</kwd><kwd>HIV</kwd><kwd>Kaposi's sarcoma</kwd><kwd>plasma HIV RNA</kwd><kwd>Africa</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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