{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T04:12:42Z","timestamp":1777349562686,"version":"3.51.4"},"reference-count":161,"publisher":"S. Karger AG","issue":"4","license":[{"start":{"date-parts":[[2009,1,1]],"date-time":"2009-01-01T00:00:00Z","timestamp":1230768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2009,1,1]],"date-time":"2009-01-01T00:00:00Z","timestamp":1230768000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int Arch Allergy Immunol"],"published-print":{"date-parts":[[2009]]},"abstract":"<jats:p>One of the great advances in clinical medicine was the recognition of the pleomorphism of the immune response and the multiple afferent and efferent limbs of antigen processing and responsiveness. A significant contribution to this understanding was derived from studies of human immunodeficiency states, including both inherited and acquired syndromes. Amongst these syndromes, one of the most common, and least understood, is common variable immune deficiency (CVID). CVID is a syndrome that leads to a reduction in serum immunoglobulins and complications including recurrent infections. Management includes immunoglobulin replacement therapy; however, patients with CVID are at risk for complications of exogenous immunoglobulin administration as well as CVID-associated diseases such as autoimmune processes and malignancies. To assess the current state of knowledge in the field, we performed a literature review of a total of 753 publications covering the period of 1968 until 2008. From this list, 189 publications were selected for discussion. In this review, we demonstrate that while the molecular basis of CVID in many cases remains incompletely understood, significant strides have been made and it is now clear that there is involvement of several pathways of immune activation, with contributions from both T and B cells. Furthermore, despite the current gaps in our knowledge of the molecular pathogenesis of the syndrome, there have been dramatic advances in management that have led to improved survival and significantly reduced morbidity in affected patients.<\/jats:p>","DOI":"10.1159\/000226232","type":"journal-article","created":{"date-parts":[[2009,7,6]],"date-time":"2009-07-06T10:41:43Z","timestamp":1246876903000},"page":"311-324","source":"Crossref","is-referenced-by-count":34,"title":["Common Variable Immunodeficiency: Etiological and Treatment Issues"],"prefix":"10.1159","volume":"150","author":[{"given":"Sean","family":"Deane","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Selmi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stanley M.","family":"Naguwa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanne S.","family":"Teuber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Eric","family":"Gershwin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2009,7,1]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1056%2FNEJM197305032881814"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016%2FS0167-5699%2897%2901086-4"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1002%2F1521-4141%28200009%2930%3A9%3C2632%3A%3AAID-IMMU2632%3E3.0.CO%3B2-C"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016%2FS1526-0542%2804%2990043-7"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1038%2Fni902"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1203%2F00006450-199304001-00006"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1097%2F01.bor.0000231906.12172.6e"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1007%2Fs10238-004-0027-2"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.gde.2007.04.002"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1016%2FS1081-1206%2810%2961142-8"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1007%2Fs12026-007-8000-2"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1097%2F00008480-199412000-00011"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1046%2Fj.1365-2249.2000.01131.x"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1006%2Fclim.1999.4725"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1016%2FS1081-1206%2810%2960638-2"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1128%2FCVI.13.3.329-332.2006"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.jaci.2004.01.761"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1016%2FS1081-1206%2810%2960665-5"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1111%2Fj.1365-2249.2004.02558.x"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.jaci.2006.01.008"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1006%2Fclim.1999.4799"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1111%2Fj.1365-2249.2004.02581.x"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1097%2F01.all.0000191888.97397.b3"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1159%2F000135702"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1046%2Fj.1365-2249.2001.01556.x"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1007%2Fs10875-007-9075-1"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.jaci.2007.08.053"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1016%2FS1081-1206%2810%2960853-8"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1016%2FS0009-9260%2805%2980501-X"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1016%2F0002-9343%2876%2990173-X"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1016%2FS0091-6749%2899%2970085-0"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1111%2Fj.1365-2249.2008.03700.x"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1053%2Frmed.2000.1020"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1378%2Fchest.106.2.490"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1016%2FS1081-1206%2810%2961096-4"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.1016%2FS0022-3476%2899%2970246-5"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.1016%2F0091-6749%2891%2990306-9"},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.1097%2F01.rct.0000228163.08968.26"},{"key":"ref39","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.jaci.2004.05.057"},{"key":"ref40","doi-asserted-by":"publisher","DOI":"10.1016%2FS1081-1206%2810%2962316-2"},{"key":"ref41","doi-asserted-by":"publisher","DOI":"10.1007%2Fs11882-005-0008-x"},{"key":"ref42","doi-asserted-by":"publisher","DOI":"10.1097%2FPAS.0b013e3180cab60c"},{"key":"ref43","doi-asserted-by":"publisher","DOI":"10.1097%2F01.SMJ.0000053461.31030.D7"},{"key":"ref44","doi-asserted-by":"publisher","DOI":"10.1097%2F00005792-200103000-00005"},{"key":"ref45","doi-asserted-by":"publisher","DOI":"10.1016%2F0002-9343%2888%2990016-2"},{"key":"ref46","doi-asserted-by":"publisher","DOI":"10.1111%2Fj.1872-034X.2007.00281.x"},{"key":"ref47","doi-asserted-by":"publisher","DOI":"10.1006%2Fclim.2001.5132"},{"key":"ref48","doi-asserted-by":"publisher","DOI":"10.1016%2FS1081-1206%2810%2961228-8"},{"key":"ref49","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.autrev.2006.03.010"},{"key":"ref50","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.jaci.2006.12.370"},{"key":"ref51","doi-asserted-by":"publisher","DOI":"10.1016%2FS1081-1206%2810%2960697-7"},{"key":"ref52","doi-asserted-by":"publisher","DOI":"10.1054%2Fblre.2001.0185"},{"key":"ref53","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.yexmp.2008.03.011"},{"key":"ref54","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.it.2006.12.006"},{"key":"ref55","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.jaut.2008.04.026"},{"key":"ref56","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.jaut.2008.04.007"},{"key":"ref57","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.jaut.2008.04.010"},{"key":"ref58","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.jaut.2007.07.021"},{"key":"ref59","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.jaut.2008.04.011"},{"key":"ref60","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.jaut.2007.07.014"},{"key":"ref61","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.jaut.2008.04.012"},{"key":"ref62","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.jaut.2007.11.012"},{"key":"ref63","doi-asserted-by":"publisher","DOI":"10.1084%2Fjem.20040920"},{"key":"ref64","doi-asserted-by":"publisher","DOI":"10.1097%2F01.md.0000133624.65946.40"},{"key":"ref65","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.clim.2008.03.510"},{"key":"ref66","doi-asserted-by":"publisher","DOI":"10.1159%2F000029488"},{"key":"ref67","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.jaut.2005.04.006"},{"key":"ref68","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.jaci.2005.02.021"},{"key":"ref69","doi-asserted-by":"publisher","DOI":"10.1182%2Fblood-2007-06-091744"},{"key":"ref70","doi-asserted-by":"publisher","DOI":"10.1084%2Fjem.20050381"},{"key":"ref71","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.clim.2005.04.006"},{"key":"ref72","doi-asserted-by":"publisher","DOI":"10.1016%2FS0140-6736%2808%2961199-X"},{"key":"ref73","doi-asserted-by":"publisher","DOI":"10.1002%2Fajh.10050"},{"key":"ref74","doi-asserted-by":"publisher","DOI":"10.1007%2FBF00915550"},{"key":"ref75","doi-asserted-by":"publisher","DOI":"10.1016%2FS0140-6736%2885%2991037-2"},{"key":"ref76","doi-asserted-by":"publisher","DOI":"10.1046%2Fj.1365-2249.2002.02004.x"},{"key":"ref77","doi-asserted-by":"publisher","DOI":"10.1046%2Fj.1365-2796.1996.514837000.x"},{"key":"ref78","doi-asserted-by":"publisher","DOI":"10.1016%2FS1081-1206%2810%2960695-3"},{"key":"ref79","doi-asserted-by":"publisher","DOI":"10.1007%2Fs10238-008-0175-x"},{"key":"ref80","doi-asserted-by":"publisher","DOI":"10.1200%2FJCO.2005.04.3133"},{"key":"ref81","doi-asserted-by":"publisher","DOI":"10.1023%2FA%3A1025373601374"},{"key":"ref82","doi-asserted-by":"publisher","DOI":"10.1182%2Fblood.V99.5.1544"},{"key":"ref83","doi-asserted-by":"publisher","DOI":"10.1080%2F00313020801911470"},{"key":"ref84","doi-asserted-by":"publisher","DOI":"10.1016%2FS0091-6749%2802%2981694-3"},{"key":"ref85","doi-asserted-by":"publisher","DOI":"10.2169%2Finternalmedicine.38.722"},{"key":"ref86","doi-asserted-by":"publisher","DOI":"10.1067%2Fmai.2001.120133"},{"key":"ref87","doi-asserted-by":"publisher","DOI":"10.1046%2Fj.1365-2249.2000.01244.x"},{"key":"ref88","doi-asserted-by":"publisher","DOI":"10.1016%2FS1081-1206%2810%2960569-8"},{"key":"ref89","doi-asserted-by":"publisher","DOI":"10.1182%2Fblood-2003-12-4420"},{"key":"ref90","doi-asserted-by":"publisher","DOI":"10.1016%2FS1081-1206%2810%2961075-7"},{"key":"ref91","doi-asserted-by":"publisher","DOI":"10.1532%2FIJH97.06095"},{"key":"ref92","doi-asserted-by":"publisher","DOI":"10.1023%2FA%3A1019982206951"},{"key":"ref93","doi-asserted-by":"publisher","DOI":"10.1186%2F1476-7961-6-5"},{"key":"ref94","doi-asserted-by":"publisher","DOI":"10.1006%2Fclim.2001.5024"},{"key":"ref95","doi-asserted-by":"publisher","DOI":"10.1186%2Frr56"},{"key":"ref96","doi-asserted-by":"publisher","DOI":"10.1007%2FBF02983239"},{"key":"ref97","doi-asserted-by":"publisher","DOI":"10.1182%2Fblood.V98.5.1321"},{"key":"ref98","doi-asserted-by":"publisher","DOI":"10.1046%2Fj.1365-2249.2001.01599.x"},{"key":"ref99","doi-asserted-by":"publisher","DOI":"10.1007%2Fs00431-002-1083-9"},{"key":"ref100","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.smim.2006.07.004"},{"key":"ref101","doi-asserted-by":"publisher","DOI":"10.1016%2F0091-6749%2893%2990178-I"},{"key":"ref102","doi-asserted-by":"publisher","DOI":"10.1111%2Fj.1365-2249.2004.02630.x"},{"key":"ref103","doi-asserted-by":"publisher","DOI":"10.1111%2Fj.1365-2249.1991.tb05704.x"},{"key":"ref104","doi-asserted-by":"publisher","DOI":"10.1038%2F16717"},{"key":"ref105","doi-asserted-by":"publisher","DOI":"10.1146%2Fannurev.immunol.20.091101.091806"},{"key":"ref106","doi-asserted-by":"publisher","DOI":"10.1111%2Fj.1365-3083.2005.001603.x"},{"key":"ref107","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.clim.2004.07.002"},{"key":"ref108","doi-asserted-by":"publisher","DOI":"10.1182%2Fblood-2005-07-2955"},{"key":"ref109","doi-asserted-by":"publisher","DOI":"10.1038%2Fsj.gene.6364431"},{"key":"ref110","doi-asserted-by":"publisher","DOI":"10.1056%2FNEJMoa051568"},{"key":"ref111","doi-asserted-by":"publisher","DOI":"10.1146%2Fannurev.immunol.18.1.393"},{"key":"ref112","doi-asserted-by":"publisher","DOI":"10.1126%2Fscience.1373518"},{"key":"ref113","doi-asserted-by":"publisher","DOI":"10.1038%2Fng0407-430"},{"key":"ref114","doi-asserted-by":"publisher","DOI":"10.1038%2Fng1601"},{"key":"ref115","doi-asserted-by":"publisher","DOI":"10.1182%2Fblood-2008-02-141937"},{"key":"ref116","doi-asserted-by":"publisher","DOI":"10.1038%2Fng1600"},{"key":"ref117","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.jaci.2007.10.001"},{"key":"ref118","doi-asserted-by":"publisher","DOI":"10.1038%2Fng0407-429"},{"key":"ref119","doi-asserted-by":"publisher","DOI":"10.1007%2Fs11882-996-0004-9"},{"key":"ref120","doi-asserted-by":"publisher","DOI":"10.1146%2Fannurev.immunol.21.120601.141152"},{"key":"ref121","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.cytogfr.2008.04.006"},{"key":"ref122","doi-asserted-by":"publisher","DOI":"10.1097%2F01.all.0000191887.89773.cc"},{"key":"ref123","doi-asserted-by":"publisher","DOI":"10.1002%2Feji.200636914"},{"key":"ref124","doi-asserted-by":"publisher","DOI":"10.1007%2Fs10875-005-5637-2"},{"key":"ref125","doi-asserted-by":"publisher","DOI":"10.1084%2Fjem.20032000"},{"key":"ref126","doi-asserted-by":"publisher","DOI":"10.1073%2Fpnas.0700815104"},{"key":"ref127","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.iac.2008.01.008"},{"key":"ref128","doi-asserted-by":"publisher","DOI":"10.1067%2Fmai.2002.124999"},{"key":"ref129","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.iac.2008.07.001"},{"key":"ref130","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.clim.2004.02.002"},{"key":"ref131","doi-asserted-by":"publisher","DOI":"10.1016%2FS1081-1206%2810%2960197-4"},{"key":"ref132","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.clim.2007.06.009"},{"key":"ref133","doi-asserted-by":"publisher","DOI":"10.1097%2F01.all.0000246619.49494.41"},{"key":"ref134","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.jaci.2004.06.053"},{"key":"ref135","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.jaci.2006.01.015"},{"key":"ref136","doi-asserted-by":"publisher","DOI":"10.1016%2F0090-1229%2886%2990133-9"},{"key":"ref137","doi-asserted-by":"publisher","DOI":"10.1007%2FBF00919386"},{"key":"ref138","doi-asserted-by":"publisher","DOI":"10.1016%2FS0091-6749%2802%2981693-1"},{"key":"ref139","doi-asserted-by":"publisher","DOI":"10.1007%2Fs00247-002-0687-6"},{"key":"ref140","doi-asserted-by":"publisher","DOI":"10.1056%2FNEJMra072149"},{"key":"ref141","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.iac.2008.01.001"},{"key":"ref142","doi-asserted-by":"publisher","DOI":"10.1093%2Fbioinformatics%2Fbtl675"},{"key":"ref143","doi-asserted-by":"publisher","DOI":"10.1093%2Fnar%2Fgkn682"},{"key":"ref144","doi-asserted-by":"publisher","DOI":"10.1126%2Fscience.7679801"},{"key":"ref145","doi-asserted-by":"publisher","DOI":"10.1016%2F0092-8674%2893%2990668-G"},{"key":"ref146","doi-asserted-by":"publisher","DOI":"10.1038%2F361541a0"},{"key":"ref147","doi-asserted-by":"publisher","DOI":"10.1073%2Fpnas.91.3.1099"},{"key":"ref148","doi-asserted-by":"publisher","DOI":"10.1038%2F361539a0"},{"key":"ref149","doi-asserted-by":"publisher","DOI":"10.1006%2Fclim.2000.4956"},{"key":"ref150","doi-asserted-by":"publisher","DOI":"10.1016%2FS0092-8674%2800%2900079-9"},{"key":"ref151","doi-asserted-by":"publisher","DOI":"10.1073%2Fpnas.221456898"},{"key":"ref152","doi-asserted-by":"publisher","DOI":"10.1172%2FJCI200318161"},{"key":"ref153","doi-asserted-by":"publisher","DOI":"10.1038%2Fni974"},{"key":"ref154","doi-asserted-by":"publisher","DOI":"10.1038%2F85277"},{"key":"ref155","doi-asserted-by":"publisher","DOI":"10.1056%2FNEJM199405263302104"},{"key":"ref156","doi-asserted-by":"publisher","DOI":"10.1016%2F0092-8674%2893%2990667-F"},{"key":"ref157","doi-asserted-by":"publisher","DOI":"10.1038%2F361226a0"},{"key":"ref158","doi-asserted-by":"publisher","DOI":"10.1038%2F2424"},{"key":"ref159","doi-asserted-by":"publisher","DOI":"10.1038%2Fnature05257"},{"key":"ref160","doi-asserted-by":"publisher","DOI":"10.1038%2F26683"},{"key":"ref161","doi-asserted-by":"publisher","DOI":"10.2165%2F00003495-200363130-00003"}],"container-title":["International Archives of Allergy and Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/226232","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/226232","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T23:03:00Z","timestamp":1745449380000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000226232"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009]]},"references-count":161,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2009,11,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000226232","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.5241151","asserted-by":"subject"}]},"ISSN":["1018-2438","1423-0097"],"issn-type":[{"value":"1018-2438","type":"print"},{"value":"1423-0097","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009]]}}}