{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T22:33:49Z","timestamp":1759962829951,"version":"3.37.3"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T00:00:00Z","timestamp":1567900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Impact Fund of Children's of Alabama"},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R24 AI067039"],"award-info":[{"award-number":["R24 AI067039"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008333","name":"University of Alabama at Birmingham","doi-asserted-by":"publisher","award":["P30 AI027767"],"award-info":[{"award-number":["P30 AI027767"]}],"id":[{"id":"10.13039\/100008333","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007812","name":"University of Washington","doi-asserted-by":"publisher","award":["P30 AI027757"],"award-info":[{"award-number":["P30 AI027757"]}],"id":[{"id":"10.13039\/100007812","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005595","name":"University of California San Diego","doi-asserted-by":"publisher","award":["P30 AI036214"],"award-info":[{"award-number":["P30 AI036214"]}],"id":[{"id":"10.13039\/100005595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005595","name":"University of California San Francisco","doi-asserted-by":"publisher","award":["P30 AI027763"],"award-info":[{"award-number":["P30 AI027763"]}],"id":[{"id":"10.13039\/100005595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008136","name":"Case Western Reserve University","doi-asserted-by":"publisher","award":["P30 AI036219"],"award-info":[{"award-number":["P30 AI036219"]}],"id":[{"id":"10.13039\/100008136","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007880","name":"Johns Hopkins University","doi-asserted-by":"publisher","award":["P30 AI094189","U01 DA036935"],"award-info":[{"award-number":["P30 AI094189","U01 DA036935"]}],"id":[{"id":"10.13039\/100007880","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007880","name":"Fenway Health\/Harvard","doi-asserted-by":"publisher","award":["P30 AI060354"],"award-info":[{"award-number":["P30 AI060354"]}],"id":[{"id":"10.13039\/100007880","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006808","name":"University of North Carolina Chapel Hill","doi-asserted-by":"publisher","award":["P30 AI50410"],"award-info":[{"award-number":["P30 AI50410"]}],"id":[{"id":"10.13039\/100006808","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,11,15]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The complement system is now a therapeutic target for the management of serious and life-threatening conditions such as paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, glomerulonephritis and other diseases caused by complement deficiencies or genetic variants. As complement therapeutics expand into more clinical conditions, monitoring complement activation is increasingly important, as is the baseline levels of complement activation fragments in blood or other body fluid levels. Although baseline complement levels have been reported in the literature, the majority of these data were generated using non-standard assays and with variable sample handling, potentially skewing results. In this study, we examined the plasma and serum levels of the soluble membrane attack complex of complement (sMAC). sMAC is formed in the fluid phase when complement is activated through the terminal pathway. It binds the regulatory proteins vitronectin and\/or clusterin and cannot insert into cell membranes, and can serve as a soluble diagnostic marker in infectious disease settings, as previously shown for intraventricular shunt infections. Here we show that in healthy adults, serum sMAC levels were significantly higher than those in plasma, that plasma sMAC levels were similar between in African Americans and Caucasians and that plasma sMAC levels increase with age. Plasma sMAC levels were significantly higher in virally suppressed people living with HIV (PLWH) compared to non-HIV infected healthy donors. More specifically, PLWH with CD4+ T cell counts below 200 had even greater sMAC levels, suggesting diagnostic value in monitoring sMAC levels in this group.<\/jats:p>","DOI":"10.1111\/cei.13366","type":"journal-article","created":{"date-parts":[[2019,8,28]],"date-time":"2019-08-28T22:42:47Z","timestamp":1567032167000},"page":"359-366","source":"Crossref","is-referenced-by-count":8,"title":["Plasma levels of soluble membrane attack complex are elevated despite viral suppression in HIV patients with poor immune reconstitution"],"prefix":"10.1093","volume":"198","author":[{"given":"T N","family":"Schein","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T E","family":"Blackburn","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S L","family":"Heath","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Disease, University of Alabama at Birmingham, Birmingham, Alabama, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7373-6778","authenticated-orcid":false,"given":"S R","family":"Barnum","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,9,8]]},"reference":[{"key":"2022011418395992100_cei13366-bib-0001","doi-asserted-by":"crossref","first-page":"262","DOI":"10.3389\/fimmu.2015.00262","article-title":"Complement System Part I - Molecular Mechanisms of Activation and Regulation","volume":"6","author":"Merle","year":"2015","journal-title":"Front Immunol"},{"key":"2022011418395992100_cei13366-bib-0002","doi-asserted-by":"crossref","first-page":"257","DOI":"10.3389\/fimmu.2015.00257","article-title":"Complement System Part II: Role in Immunity","volume":"6","author":"Merle","year":"2015","journal-title":"Front Immunol"},{"key":"2022011418395992100_cei13366-bib-0003","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.pharmthera.2016.11.014","article-title":"Complement: a primer for the coming therapeutic revolution","volume":"172","author":"Barnum","year":"2017","journal-title":"Pharmacol Ther"},{"key":"2022011418395992100_cei13366-bib-0004","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.molimm.2017.05.012","article-title":"Intracellular complement \u2013 the complosome \u2013 in immune cell regulation","volume":"89","author":"Arbore","year":"2017","journal-title":"Mol Immunol"},{"key":"2022011418395992100_cei13366-bib-0005","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fimmu.2017.00001","article-title":"Keeping it all going-complement meets metabolism","volume":"8","author":"Kolev","year":"2017","journal-title":"Front Immunol"},{"key":"2022011418395992100_cei13366-bib-0006","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1111\/j.1600-065X.2008.00641.x","article-title":"The spectrum of complement alternative pathway-mediated diseases","volume":"223","author":"Holers","year":"2008","journal-title":"Immunol Rev"},{"key":"2022011418395992100_cei13366-bib-0007","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1016\/j.imbio.2012.07.021","article-title":"Complement dysregulation and disease: from genes and proteins to diagnostics and drugs","volume":"217","author":"de Cordoba","year":"2012","journal-title":"Immunobiology"},{"key":"2022011418395992100_cei13366-bib-0008","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s00281-017-0663-8","article-title":"Diseases of complement dysregulation \u2013 an overview","volume":"40","author":"Wong","year":"2018","journal-title":"Semin Immunopathol"},{"key":"2022011418395992100_cei13366-bib-0009","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1038\/nrd4657","article-title":"Complement, a target for therapy in inflammatory and degenerative diseases","volume":"14","author":"Morgan","year":"2015","journal-title":"Nat Rev Drug Discovery"},{"key":"2022011418395992100_cei13366-bib-0010","article-title":"Complement as a diagnostic tool in immunopathology","author":"Lopez-Lera","year":"2018","journal-title":"Semin Cell Dev Biol"},{"key":"2022011418395992100_cei13366-bib-0011","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.molimm.2018.06.001","article-title":"Complement analysis in the era of targeted therapeutics","volume":"102","author":"Prohaszka","year":"2018","journal-title":"Mol Immunol"},{"key":"2022011418395992100_cei13366-bib-0012","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1016\/j.imbio.2016.06.008","article-title":"Complement analysis 2016: Clinical indications, laboratory diagnostics and quality control","volume":"221","author":"Prohaszka","year":"2016","journal-title":"Immunobiology"},{"key":"2022011418395992100_cei13366-bib-0013","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1084\/jem.138.2.438","article-title":"The membrane attack mechanism of complement. Verification of a stable C5\u20139 complex in free solution","volume":"138","author":"Kolb","year":"1973","journal-title":"J Exp Med"},{"key":"2022011418395992100_cei13366-bib-0014","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.4049\/jimmunol.120.6.1841","article-title":"The C5b\u20136 complex: formation, isolation, and inhibition of its activity by lipoprotein and the S-protein of human serum","volume":"120","author":"Podack","year":"1978","journal-title":"J Immunol"},{"key":"2022011418395992100_cei13366-bib-0015","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.celrep.2012.02.003","article-title":"Assembly and regulation of the membrane attack complex based on structures of C5b6 and sC5b9","volume":"1","author":"Hadders","year":"2012","journal-title":"Cell Rep"},{"key":"2022011418395992100_cei13366-bib-0016","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1111\/j.1365-3083.1985.tb01871.x","article-title":"Quantification of the terminal complement complex in human plasma by an enzyme-linked immunosorbent assay based on monoclonal antibodies against a neoantigen of the complex","volume":"22","author":"Mollnes","year":"1985","journal-title":"Scand J Immunol"},{"key":"2022011418395992100_cei13366-bib-0017","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1111\/j.1365-3083.1985.tb01870.x","article-title":"Monoclonal antibodies recognizing a neoantigen of poly(C9) detect the human terminal complement complex in tissue and plasma","volume":"22","author":"Mollnes","year":"1985","journal-title":"Scand J Immunol"},{"key":"2022011418395992100_cei13366-bib-0018","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.immuni.2016.08.003","article-title":"Complement-mediated regulation of metabolism and basic cellular process","volume":"45","author":"Hess","year":"2016","journal-title":"Immunity"},{"key":"2022011418395992100_cei13366-bib-0019","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/0022-1759(83)90088-1","article-title":"A simple immunoradiometric assay for the terminal SC5b-9 complex of human complement","volume":"57","author":"Bhakdi","year":"1983","journal-title":"J Immunol Methods"},{"key":"2022011418395992100_cei13366-bib-0020","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/0022-1759(87)90134-7","article-title":"Sensitive ELISA for quantitating the terminal membrane C5b-9 and fluid-phase SC5b-9 complex of human complement","volume":"99","author":"Hugo","year":"1987","journal-title":"J Immunol Methods"},{"key":"2022011418395992100_cei13366-bib-0021","first-page":"13","article-title":"Level of complement activity predicts cardiac dysfunction after acute myocardial infarction treated with primary percutaneous coronary intervention","volume":"21","author":"Haahr-Pedersen","year":"2009","journal-title":"J Invasive Cardiol"},{"key":"2022011418395992100_cei13366-bib-0022","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1309\/AJCPXPD7ZQXNTIAL","article-title":"Effect of blood sampling, processing, and storage on the measurement of complement activation biomarkers","volume":"143","author":"Yang","year":"2015","journal-title":"Am J Clin Pathol"},{"key":"2022011418395992100_cei13366-bib-0023","first-page":"484","article-title":"Effect of time, temperature and anticoagulants on in vitro complement activation: consequences for collection and preservation of samples to be examined for complement activation","volume":"73","author":"Mollnes","year":"1988","journal-title":"Clin Exp Immunol"},{"key":"2022011418395992100_cei13366-bib-0024","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.molimm.2013.05.221","article-title":"An international serum standard for application in assays to detect human complement activation products","volume":"56","author":"Bergseth","year":"2013","journal-title":"Mol Immunol"},{"key":"2022011418395992100_cei13366-bib-0025","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/0022-1759(86)90409-6","article-title":"An enzyme-linked immunoabsorbent assay for the quantitation of the terminal complement complex from cell membranes or in activated human sera","volume":"95","author":"Gawryl","year":"1986","journal-title":"J Immunol Methods"},{"key":"2022011418395992100_cei13366-bib-0026","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s11904-017-0356-x","article-title":"Inflammation, immune activation, and antiretroviral therapy in HIV","volume":"14","author":"Hileman","year":"2017","journal-title":"Curr HIV\/AIDS Rep"},{"key":"2022011418395992100_cei13366-bib-0027","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1097\/COH.0b013e3282f9ae9c","article-title":"The mucosal barrier and immune activation in HIV pathogenesis","volume":"3","author":"Brenchley","year":"2008","journal-title":"Curr Opin HIV AIDS"},{"key":"2022011418395992100_cei13366-bib-0028","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/mi.2007.1","article-title":"HIV infection and the gastrointestinal immune system","volume":"1","author":"Brenchley","year":"2008","journal-title":"Mucosal Immunol"},{"key":"2022011418395992100_cei13366-bib-0029","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1111\/imr.12065","article-title":"Immune activation and HIV persistence: implications for curative approaches to HIV infection","volume":"254","author":"Klatt","year":"2013","journal-title":"Immunol Rev"},{"key":"2022011418395992100_cei13366-bib-0030","doi-asserted-by":"crossref","first-page":"241","DOI":"10.3389\/fimmu.2017.00241","article-title":"HIV infection and compromised mucosal immunity: oral manifestations and systemic inflammation","volume":"8","author":"Heron","year":"2017","journal-title":"Front Immunol"},{"key":"2022011418395992100_cei13366-bib-0031","doi-asserted-by":"crossref","first-page":"5628","DOI":"10.4049\/jimmunol.0903678","article-title":"Molecular intercommunication between the complement and coagulation systems","volume":"185","author":"Amara","year":"2010","journal-title":"J Immunol"},{"key":"2022011418395992100_cei13366-bib-0032","first-page":"2664","article-title":"Age and sex-associated changes of complement activity and complement levels in a healthy Caucasian population. Front","volume":"9","author":"Gaya de Costa","year":"2018","journal-title":"Immunol"},{"key":"2022011418395992100_cei13366-bib-0033","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.molimm.2016.06.004","article-title":"Sex matters: systemic complement activity of female C57BL\/6J and BALB\/cJ mice is limited by serum terminal pathway components","volume":"76","author":"Kotimaa","year":"2016","journal-title":"Mol Immunol"},{"key":"2022011418395992100_cei13366-bib-0034","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s10522-015-9578-8","article-title":"Inflammaging decreases adaptive and innate immune responses in mice and humans","volume":"17","author":"Frasca","year":"2016","journal-title":"Biogerontology"},{"key":"2022011418395992100_cei13366-bib-0035","doi-asserted-by":"crossref","DOI":"10.1016\/j.smim.2018.09.003","article-title":"The integration of inflammaging in age-related diseases","author":"Fulop","year":"2018","journal-title":"Semin Immunol"},{"key":"2022011418395992100_cei13366-bib-0036","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1159\/000236616","article-title":"HIV and complement: role of the complement system in HIV infection","volume":"103","author":"Marschang","year":"1994","journal-title":"Int Arch Allergy Immunol"},{"key":"2022011418395992100_cei13366-bib-0037","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1159\/000070211","article-title":"Complement in different stages of HIV infection and pathogenesis","volume":"130","author":"Speth","year":"2003","journal-title":"Int Arch Allergy Immunol"},{"issue":"Suppl 2","key":"2022011418395992100_cei13366-bib-0038","doi-asserted-by":"crossref","first-page":"S77","DOI":"10.1016\/S0264-410X(03)00203-2","article-title":"Role of complement in the control of HIV dynamics and pathogenesis","volume":"21","author":"Stoiber","year":"2003","journal-title":"Vaccine"},{"key":"2022011418395992100_cei13366-bib-0039","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.biopha.2006.07.087","article-title":"HIV and complement: hijacking an immune defense","volume":"60","author":"Datta","year":"2006","journal-title":"Biomed Pharmacother"},{"key":"2022011418395992100_cei13366-bib-0040","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.clim.2014.06.002","article-title":"The lectin pathway of complement: advantage or disadvantage in HIV pathogenesis?","volume":"154","author":"Ballegaard","year":"2014","journal-title":"Clin Immunol"},{"key":"2022011418395992100_cei13366-bib-0041","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1038\/cmi.2010.8","article-title":"The good and evil of complement activation in HIV-1 infection","volume":"7","author":"Yu","year":"2010","journal-title":"Cell Mol Immunol"},{"key":"2022011418395992100_cei13366-bib-0042","doi-asserted-by":"crossref","first-page":"e0166496","DOI":"10.1371\/journal.pone.0166496","article-title":"Gut homing CD4+ and CD8+ T-cell frequencies in HIV infected individuals on antiretroviral treatment","volume":"11","author":"Briceno","year":"2016","journal-title":"PLOS ONE"},{"key":"2022011418395992100_cei13366-bib-0043","doi-asserted-by":"crossref","first-page":"438","DOI":"10.3389\/fimmu.2016.00438","article-title":"CD4(+) T follicular helper and IgA(+) B cell numbers in gut biopsies from HIV-infected subjects on antiretroviral therapy are similar to HIV-uninfected individuals","volume":"7","author":"Zaunders","year":"2016","journal-title":"Front Immunol"},{"key":"2022011418395992100_cei13366-bib-0044","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1097\/QAI.0000000000000943","article-title":"Brief report: a high rate of beta7+ gut-homing lymphocytes in HIV-infected immunological nonresponders is associated with poor CD4 T-cell recovery during suppressive HAART","volume":"72","author":"Girard","year":"2016","journal-title":"J Acquir Immune Defic Syndr"},{"key":"2022011418395992100_cei13366-bib-0045","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/nrneph.2017.156","article-title":"The renaissance of complement therapeutics","volume":"14","author":"Ricklin","year":"2018","journal-title":"Nat Rev Nephrol"}],"container-title":["Clinical and Experimental Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cei.13366","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cei.13366","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/198\/3\/359\/42196305\/cei13366.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/198\/3\/359\/42196305\/cei13366.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T15:53:02Z","timestamp":1695138782000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cei\/article\/198\/3\/359\/6402568"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,8]]},"references-count":45,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,9,8]]},"published-print":{"date-parts":[[2019,11,15]]}},"URL":"https:\/\/doi.org\/10.1111\/cei.13366","relation":{},"ISSN":["0009-9104","1365-2249"],"issn-type":[{"type":"print","value":"0009-9104"},{"type":"electronic","value":"1365-2249"}],"subject":[],"published-other":{"date-parts":[[2019,12]]},"published":{"date-parts":[[2019,9,8]]}}}