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Here we study patients suffering from recurrent bacterial, viral and\n                    <jats:italic>Cryptosporidium<\/jats:italic>\n                    infections, and identify a biallelic mutation in the\n                    <jats:italic>MAP3K14<\/jats:italic>\n                    gene encoding NIK (NF-\u03baB-inducing kinase). Loss of kinase activity of mutant NIK, predicted by\n                    <jats:italic>in silico<\/jats:italic>\n                    analysis and confirmed by functional assays, leads to defective activation of both canonical and non-canonical NF-\u03baB signalling. Patients with mutated\n                    <jats:italic>NIK<\/jats:italic>\n                    exhibit B-cell lymphopenia, decreased frequencies of class-switched memory B cells and hypogammaglobulinemia due to impaired B-cell survival, and impaired ICOSL expression. Although overall T-cell numbers are normal, both follicular helper and memory T cells are perturbed. Natural killer (NK) cells are decreased and exhibit defective activation, leading to impaired formation of NK-cell immunological synapses. Collectively, our data illustrate the non-redundant role for NIK in human immune responses, demonstrating that loss-of-function mutations in\n                    <jats:italic>NIK<\/jats:italic>\n                    can cause multiple aberrations of lymphoid immunity.\n                  <\/jats:p>","DOI":"10.1038\/ncomms6360","type":"journal-article","created":{"date-parts":[[2014,11,19]],"date-time":"2014-11-19T06:57:06Z","timestamp":1416380226000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":150,"title":["Biallelic loss-of-function mutation in NIK causes a primary immunodeficiency with multifaceted aberrant lymphoid immunity"],"prefix":"10.1038","volume":"5","author":[{"given":"Katharina L.","family":"Willmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Klaver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Figen","family":"Do\u011fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisangela","family":"Santos-Valente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech","family":"Garncarz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Bilic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Mace","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Salzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Dom\u00ednguez Conde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiko","family":"Sic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"M\u00e1jek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinaki P.","family":"Banerjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory I.","family":"Vladimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u015eule","family":"Haskolo\u011flu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Musa","family":"G\u00f6kalp Bolkent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alphan","family":"K\u00fcpesiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Condino-Neto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Colinge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio","family":"Superti-Furga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winfried F.","family":"Pickl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menno C.","family":"van Zelm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Eibel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan S.","family":"Orange","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aydan","family":"Ikincio\u011fullar\u0131","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaan","family":"Boztu\u011f","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,11,19]]},"reference":[{"key":"BFncomms6360_CR1","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1016\/j.jaci.2013.01.046","volume":"131","author":"K Pieper","year":"2013","unstructured":"Pieper, K., Grimbacher, B. & Eibel, H. 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