{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:32:17Z","timestamp":1789014737090,"version":"build-2803163510"},"reference-count":46,"publisher":"Cold Spring Harbor Laboratory","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cold Spring Harb Mol Case Stud"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:p>Acquired aplastic anemia (AA) is a life-threatening bone marrow failure caused by an autoimmune cytotoxic T lymphocyte attack on hematopoietic stem and progenitor cells. Factors contributing to aberrant autoimmune activation in AA include a deficit of T regulatory cells and high levels of inflammatory cytokines. Several acquired conditions of immune dysregulation and genetic polymorphisms in inflammatory cytokines and human leukocyte antigen genes have been linked to an increased risk of AA. However, AA has not been reported in patients with Mendelian disorders of immune regulation. Here we report a patient with familial common variable immunodeficiency (CVID) caused by a pathogenic variant in<jats:italic>NFKB1<\/jats:italic>, who developed AA as an adult. The patient had a difficult clinical course and was unable to tolerate standard AA therapy with cyclosporine A and eltrombopag, with complications attributed in part to the effect of cyclosporine A on NF-\u03baB signaling. Our case suggests a novel link between genetic disorders of immune regulation and AA and highlights the importance of recognizing inherited autoimmunity syndromes in AA patients for the selection of optimal therapy and prognostic counseling.<\/jats:p>","DOI":"10.1101\/mcs.a005769","type":"journal-article","created":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T01:35:25Z","timestamp":1600997725000},"page":"a005769","source":"Crossref","is-referenced-by-count":10,"title":["Aplastic anemia in a patient with CVID due to NFKB1 haploinsufficiency"],"prefix":"10.1101","volume":"6","author":[{"given":"Tammarah","family":"Sklarz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6975-9168","authenticated-orcid":false,"given":"Stephanie N.","family":"Hurwitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha L.","family":"Stanley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4476-1309","authenticated-orcid":false,"given":"Jane","family":"Juusola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1669-468X","authenticated-orcid":false,"given":"Adam","family":"Bagg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Babushok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2020,9,24]]},"reference":[{"key":"2021112506221607000_6.6.a005769.1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2017010918"},{"key":"2021112506221607000_6.6.a005769.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199704103361504"},{"key":"2021112506221607000_6.6.a005769.3","doi-asserted-by":"publisher","DOI":"10.1111\/febs.13627"},{"key":"2021112506221607000_6.6.a005769.4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0077749"},{"key":"2021112506221607000_6.6.a005769.5","doi-asserted-by":"publisher","DOI":"10.1136\/pgmj.50.582.215"},{"key":"2021112506221607000_6.6.a005769.6","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2018-0574"},{"key":"2021112506221607000_6.6.a005769.7","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0b013e3182899e78"},{"key":"2021112506221607000_6.6.a005769.8","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2556"},{"key":"2021112506221607000_6.6.a005769.9","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2004.05102.x"},{"key":"2021112506221607000_6.6.a005769.10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2006.03314.x"},{"key":"2021112506221607000_6.6.a005769.11","doi-asserted-by":"publisher","DOI":"10.3791\/52758"},{"key":"2021112506221607000_6.6.a005769.12","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1994.tb06329.x"},{"key":"2021112506221607000_6.6.a005769.13","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.226134"},{"key":"2021112506221607000_6.6.a005769.14","doi-asserted-by":"publisher","DOI":"10.1038\/nature15393"},{"key":"2021112506221607000_6.6.a005769.15","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1409405"},{"key":"2021112506221607000_6.6.a005769.16","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a000182"},{"key":"2021112506221607000_6.6.a005769.17","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V70.6.1718.1718"},{"key":"2021112506221607000_6.6.a005769.18","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1408617"},{"key":"2021112506221607000_6.6.a005769.19","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.05.004"},{"key":"2021112506221607000_6.6.a005769.20","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2012.01106.x"},{"key":"2021112506221607000_6.6.a005769.21","doi-asserted-by":"publisher","DOI":"10.1038\/ni0302-221"},{"key":"2021112506221607000_6.6.a005769.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.10.054"},{"key":"2021112506221607000_6.6.a005769.23","doi-asserted-by":"publisher","DOI":"10.1080\/02688697.2018.1540764"},{"key":"2021112506221607000_6.6.a005769.24","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057"},{"key":"2021112506221607000_6.6.a005769.25","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0215021"},{"key":"2021112506221607000_6.6.a005769.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2019.11.051"},{"key":"2021112506221607000_6.6.a005769.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2016.11.012"},{"key":"2021112506221607000_6.6.a005769.28","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830270703"},{"key":"2021112506221607000_6.6.a005769.29","doi-asserted-by":"publisher","DOI":"10.1053\/bega.2000.0172"},{"key":"2021112506221607000_6.6.a005769.30","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(97)00930-7"},{"key":"2021112506221607000_6.6.a005769.31","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.5310"},{"key":"2021112506221607000_6.6.a005769.32","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V84.12.4257.bloodjournal84124257"},{"key":"2021112506221607000_6.6.a005769.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2016.07.011"},{"key":"2021112506221607000_6.6.a005769.34","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00189"},{"key":"2021112506221607000_6.6.a005769.35","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-08-1041"},{"key":"2021112506221607000_6.6.a005769.36","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16724-X"},{"key":"2021112506221607000_6.6.a005769.37","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-018-0060-1"},{"key":"2021112506221607000_6.6.a005769.38","doi-asserted-by":"crossref","first-page":"4685","DOI":"10.4049\/jimmunol.155.10.4685","article-title":"Regulation of IkB \u03b1 phosphorylation by PKC- and Ca2+-dependent signal transduction pathways","volume":"155","year":"1995","journal-title":"J Immunol"},{"key":"2021112506221607000_6.6.a005769.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.01.039"},{"key":"2021112506221607000_6.6.a005769.40","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132641"},{"key":"2021112506221607000_6.6.a005769.41","doi-asserted-by":"publisher","DOI":"10.1084\/jem.181.3.1091"},{"key":"2021112506221607000_6.6.a005769.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.11.029"},{"key":"2021112506221607000_6.6.a005769.43","doi-asserted-by":"publisher","DOI":"10.3109\/07853890.2014.915579"},{"key":"2021112506221607000_6.6.a005769.44","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1413485"},{"key":"2021112506221607000_6.6.a005769.45","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-11-752378"},{"key":"2021112506221607000_6.6.a005769.46","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00391"}],"container-title":["Molecular Case Studies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/mcs.a005769","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,8]],"date-time":"2023-10-08T06:36:32Z","timestamp":1696746992000},"score":1,"resource":{"primary":{"URL":"http:\/\/molecularcasestudies.cshlp.org\/lookup\/doi\/10.1101\/mcs.a005769"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,24]]},"references-count":46,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,12,17]]},"published-print":{"date-parts":[[2020,12]]}},"alternative-id":["10.1101\/mcs.a005769"],"URL":"https:\/\/doi.org\/10.1101\/mcs.a005769","relation":{},"ISSN":["2373-2865","2373-2873"],"issn-type":[{"value":"2373-2865","type":"print"},{"value":"2373-2873","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,24]]}}}