{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T23:48:02Z","timestamp":1790034482211,"version":"4.0.1"},"reference-count":26,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,7,4]],"date-time":"2018-07-04T00:00:00Z","timestamp":1530662400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20 GM104317"],"award-info":[{"award-number":["P20 GM104317"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000061","name":"Fogarty International Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000061","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 AI027757"],"award-info":[{"award-number":["P30 AI027757"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Spontaneous interferon\u2010\u03b3 (IFN\u03b3) released detected by enzyme\u2010linked immunospot (ELISpot) assays may be a biological phenomenon. Markers of immune activation levels were assessed as correlates of high background among individuals in Kenya.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Couples concordantly seronegative for HIV\u20101 were enrolled. IFN\u2010\u03b3 ELISpot assays were conducted and negative control wells were categorized as having either high or low background (\u226550 and &lt;50\u2009SFU\/10<jats:sup>6<\/jats:sup> peripheral blood mononuclear cells [PBMC], respectively). PBMC were stained for CD4, CD8, and immune activation markers (CD38 and HLA\u2010DR) and analyzed using flow cytometry. Proportions of activated T\u2010cells were compared between those with low and high background by Mann\u2013Whitney U test. Correlates of background SFU and immune activation were assessed using regression models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 58 individuals, 14 (24%) had high background. Frequencies of CD4<jats:sup>+<\/jats:sup>CD38<jats:sup>+<\/jats:sup>HLA\u2010DR<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup>CD38<jats:sup>+<\/jats:sup>HLA\u2010DR<jats:sup>+<\/jats:sup> cells were higher in individuals with high background compared to those with low background (<jats:italic>P\u2009<\/jats:italic>=\u20090.02). Higher background SFU was associated with history of sexually transmitted infections (<jats:italic>P\u2009<\/jats:italic>=\u20090.03), and illness in the past 3 months (<jats:italic>P\u2009<\/jats:italic>=\u20090.005), in addition to increased levels of activated CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> cells (<jats:italic>P<\/jats:italic> range\u2009=\u20090.008\u20130.03). Female gender and male circumcision decreased levels of CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> immune activation (<jats:italic>P<\/jats:italic> range\u2009=\u20090.002\u20130.03). Additionally, higher background SFU and activated CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> cells were individually associated with positive ELISpot responses to HIV\u20101 peptide pools (<jats:italic>P<\/jats:italic> range\u2009=\u20090.01\u20130.03).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings suggest that increased basal immune responses may be a biological mechanism contributing to higher background ELISpot SFU. Systematic exclusion of data from individuals with increased background in IFN\u2010\u03b3 release assays may bias results in population\u2010based studies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.231","type":"journal-article","created":{"date-parts":[[2018,7,5]],"date-time":"2018-07-05T03:58:07Z","timestamp":1530763087000},"page":"392-401","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["High background in ELISpot assays is associated with elevated levels of immune activation in HIV\u20101\u2010seronegative individuals in Nairobi"],"prefix":"10.1002","volume":"6","author":[{"given":"Amy Y.","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Epidemiology University of Washington Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen C.","family":"De Rosa","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine University of Washington Seattle Washington USA"},{"name":"Vaccine and Infectious Disease Division Fred Hutchinson Cancer Research Center Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon L.","family":"Guthrie","sequence":"additional","affiliation":[{"name":"Department of Epidemiology University of Washington Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert Y.","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Washington Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rose","family":"Kerubo\u2010Bosire","sequence":"additional","affiliation":[{"name":"Centre for Public Health Research Kenya Medical Research Institute Nairobi Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbra A.","family":"Richardson","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division Fred Hutchinson Cancer Research Center Seattle Washington USA"},{"name":"Department of Global Health University of Washington Seattle Washington USA"},{"name":"Department of Biostatistics University of Washington Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Kiarie","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology Kenyatta National Hospital Nairobi Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carey","family":"Farquhar","sequence":"additional","affiliation":[{"name":"Department of Epidemiology University of Washington Seattle Washington USA"},{"name":"Department of Medicine University of Washington Seattle Washington USA"},{"name":"Department of Global Health University of Washington Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5244-8681","authenticated-orcid":false,"given":"Barbara","family":"Lohman\u2010Payne","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Washington Seattle Washington USA"},{"name":"Department of Global Health University of Washington Seattle Washington USA"},{"name":"Department of Paediatrics and Child Health University of Nairobi Nairobi Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,7,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(97)00184-1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(00)00305-7"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.7"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2005.21.68"},{"key":"e_1_2_9_6_1","unstructured":"Oxford Immunotec. 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