{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T23:55:29Z","timestamp":1792022129522,"version":"4.4.0"},"reference-count":69,"publisher":"Rockefeller University Press","issue":"6","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,6,1]]},"abstract":"<jats:p>Inherited, complete deficiency of human HOIL-1, a component of the linear ubiquitination chain assembly complex (LUBAC), underlies autoinflammation, infections, and amylopectinosis. We report the clinical description and molecular analysis of a novel inherited disorder of the human LUBAC complex. A patient with multiorgan autoinflammation, combined immunodeficiency, subclinical amylopectinosis, and systemic lymphangiectasia, is homozygous for a mutation in HOIP, the gene encoding the catalytic component of LUBAC. The missense allele (L72P, in the PUB domain) is at least severely hypomorphic, as it impairs HOIP expression and destabilizes the whole LUBAC complex. Linear ubiquitination and NF-\u03baB activation are impaired in the patient\u2019s fibroblasts stimulated by IL-1\u03b2 or TNF. In contrast, the patient\u2019s monocytes respond to IL-1\u03b2 more vigorously than control monocytes. However, the activation and differentiation of the patient\u2019s B cells are impaired in response to CD40 engagement. These cellular and clinical phenotypes largely overlap those of HOIL-1-deficient patients. Clinical differences between HOIL-1- and HOIP-mutated patients may result from differences between the mutations, the loci, or other factors. Our findings show that human HOIP is essential for the assembly and function of LUBAC and for various processes governing inflammation and immunity in both hematopoietic and nonhematopoietic cells.<\/jats:p>","DOI":"10.1084\/jem.20141130","type":"journal-article","created":{"date-parts":[[2015,5,26]],"date-time":"2015-05-26T01:51:18Z","timestamp":1432605078000},"page":"939-951","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":291,"title":["Human HOIP and LUBAC deficiency underlies autoinflammation, immunodeficiency, amylopectinosis, and lymphangiectasia"],"prefix":"10.1084","volume":"212","author":[{"given":"Bertrand","family":"Boisson","sequence":"first","affiliation":[{"name":"St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY 10065 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Laplantine","sequence":"additional","affiliation":[{"name":"Laboratory of Signaling and Pathogenesis, Centre National de la Recherche Scientifique, UMR 3691, Institut Pasteur, 75724 Paris, France 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry","family":"Dobbs","sequence":"additional","affiliation":[{"name":"Division of Immunology and The Manton Center for Orphan Disease Research 3 , 4 , 5"},{"name":"Department of Pathology 3 , 4 , 5"},{"name":"Division of Hematology-Oncology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115 3 , 4 , 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Cobat","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale UMR1163 6 ; 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