{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T03:57:51Z","timestamp":1789531071281,"version":"build-2803163510"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"25","license":[{"start":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T00:00:00Z","timestamp":1591660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Division of Intramural Research, National Human Genome Research Institute","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Rheumatology, Boston, Children's Hospital","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"The Childhood Arthritis and Rheumatology Research Alliance","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Private donation from family of child with PFAPA","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"National Institutes of Health Director Challenge Fund","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Istanbul University Research Fund","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,6,23]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    In this report we identify genetic susceptibility variants for periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome, the most common periodic fever syndrome in children. PFAPA shares risk loci at\n                    <jats:italic>IL12A<\/jats:italic>\n                    ,\n                    <jats:italic>STAT4, IL10<\/jats:italic>\n                    , and\n                    <jats:italic>CCR1-CCR3<\/jats:italic>\n                    with Beh\u00e7et\u2019s disease and recurrent aphthous stomatitis, defining a family of Beh\u00e7et\u2019s spectrum disorders. Differential\n                    <jats:italic>HLA<\/jats:italic>\n                    associations along this spectrum may determine where individual phenotypes fall among the Beh\u00e7et\u2019s spectrum disorders.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2002051117","type":"journal-article","created":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T16:25:14Z","timestamp":1591719914000},"page":"14405-14411","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":109,"title":["Common genetic susceptibility loci link PFAPA syndrome, Beh\u00e7et\u2019s disease, and recurrent aphthous stomatitis"],"prefix":"10.1073","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6451-8173","authenticated-orcid":false,"given":"Kalpana","family":"Manthiram","sequence":"first","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Preite","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;"},{"name":"National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma","family":"Dedeoglu","sequence":"additional","affiliation":[{"name":"Division of Immunology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4320-8632","authenticated-orcid":false,"given":"Selcan","family":"Demir","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology, Hacettepe University Faculty of Medicine, 06100 Ankara, Turkey;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2883-7868","authenticated-orcid":false,"given":"Seza","family":"Ozen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology, Hacettepe University Faculty of Medicine, 06100 Ankara, Turkey;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3912-9832","authenticated-orcid":false,"given":"Kathryn M.","family":"Edwards","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8452-9937","authenticated-orcid":false,"given":"Sivia","family":"Lapidus","sequence":"additional","affiliation":[{"name":"Division of Pediatric Rheumatology, Joseph M. Sanzari Children\u2019s Hospital, Hackensack Meridian Health, Hackensack, NJ 07601;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9706-9490","authenticated-orcid":false,"given":"Alexander E.","family":"Katz","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The Genomic Ascertainment Cohort","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Henry M.","family":"Feder","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Connecticut Children\u2019s Medical Center, Hartford, CT 06106;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maranda","family":"Lawton","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Communication Enhancement, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg R.","family":"Licameli","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Communication Enhancement, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter F.","family":"Wright","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Le","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6925-6130","authenticated-orcid":false,"given":"Karyl S.","family":"Barron","sequence":"additional","affiliation":[{"name":"National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda K.","family":"Ombrello","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverly","family":"Barham","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Romeo","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Jones","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6714-4170","authenticated-orcid":false,"given":"Hemalatha","family":"Srinivasalu","sequence":"additional","affiliation":[{"name":"Division of Pediatric Rheumatology, Children\u2019s National Hospital, The George Washington University School of Medicine and Health Sciences, Washington, DC 20010;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela A.","family":"Mudd","sequence":"additional","affiliation":[{"name":"Division of Pediatric Otolaryngology, Children\u2019s National Hospital, The George Washington University School of Medicine and Health Sciences, Washington, DC 20010;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta L.","family":"DeBiasi","sequence":"additional","affiliation":[{"name":"Division of Pediatric Infectious Diseases, Children\u2019s National Hospital, The George Washington University School of Medicine and Health Sciences, Washington, DC 20010;"},{"name":"Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC 20010;"},{"name":"Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC 20010;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmet","family":"G\u00fcl","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology, Istanbul Faculty of Medicine, Istanbul University, 34093 Istanbul, Turkey;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary S.","family":"Marshall","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Louisville School of Medicine, Louisville, KY 40202;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olcay Y.","family":"Jones","sequence":"additional","affiliation":[{"name":"Division of Pediatric Rheumatology, Walter Reed National Military Medical Center, Bethesda, MD 20889;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Settara C.","family":"Chandrasekharappa","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuriy","family":"Stepanovskiy","sequence":"additional","affiliation":[{"name":"Department of Pediatric Infectious Diseases and Pediatric Immunology, Shupyk National Medical Academy of Postgraduate Education, 04112 Kiev, Ukraine;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polly J.","family":"Ferguson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela L.","family":"Schwartzberg","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;"},{"name":"National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine F.","family":"Remmers","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel L.","family":"Kastner","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"Ascher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie G.","family":"Biesecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscilla","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas P.","family":"Conrads","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer J.","family":"Johnston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander E.","family":"Katz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie L.","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. Larry","family":"Maxwell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Paschall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henoke","family":"Shiferaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyra G.","family":"Wolfsberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy S.W.","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suiyuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,6,9]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(87)80285-8"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.25.022106.141627"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2011.06.004"},{"key":"e_1_3_3_4_2","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1111\/j.1651-2227.2009.01554.x","article-title":"A clinical review of 105 patients with PFAPA (a periodic fever syndrome)","volume":"99","author":"Feder H. M.","year":"2010","unstructured":"H. M. Feder, J. C. Salazar, A clinical review of 105 patients with PFAPA (a periodic fever syndrome). Acta Paediatr. 99, 178\u2013184 (2010).","journal-title":"Acta Paediatr."},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2015-4572"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep10200"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.625"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2520"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3786"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.624"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1406575111"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-08923-6"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.9.4640"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq248"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2016.48"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1600760"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06258"},{"key":"e_1_3_3_18_2","first-page":"1078","article-title":"Criteria for diagnosis of Beh\u00e7et\u2019s disease","volume":"335","author":"International Study Group for Beh\u00e7et\u2019s Disease","year":"1990","unstructured":"International Study Group for Beh\u00e7et\u2019s Disease, Criteria for diagnosis of Beh\u00e7et\u2019s disease. Lancet 335, 1078\u20131080 (1990).","journal-title":"Lancet"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1906593116"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-015-2890-5"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/ced.12524"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1525-1470.2010.01247.x"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.24642"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.011"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1952"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06306"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3554"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12979"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201445217"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2004.00211.x"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-018-1613-0"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3885"},{"key":"e_1_3_3_33_2","first-page":"90","article-title":"Cytokine profile in PFAPA syndrome suggests continuous inflammation and reduced anti-inflammatory response","volume":"17","author":"Stojanov S.","year":"2006","unstructured":"S. Stojanov ., Cytokine profile in PFAPA syndrome suggests continuous inflammation and reduced anti-inflammatory response. Eur. Cytokine Netw. 17, 90\u201397 (2006).","journal-title":"Eur. Cytokine Netw."},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1103681108"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.07.043"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-014-2542-1"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2015.01.004"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0904-2512.2004.00089.x"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2011.04543.x"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1111\/jop.12182"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2005.01.002"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.05.029"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.134.7.827"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1408684"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1816594"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1901987"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2014.05.014"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00559.x"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.2002051117","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2002051117","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T04:30:56Z","timestamp":1723005056000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.2002051117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,9]]},"references-count":48,"journal-issue":{"issue":"25","published-print":{"date-parts":[[2020,6,23]]}},"alternative-id":["10.1073\/pnas.2002051117"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2002051117","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,9]]},"assertion":[{"value":"2020-06-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}