{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:26:39Z","timestamp":1792070799956,"version":"4.4.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T00:00:00Z","timestamp":1563840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"DOI":"10.3389\/fimmu.2019.01685","type":"journal-article","created":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T00:42:01Z","timestamp":1563842521000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Phenotypic Expansion in Nasu-Hakola Disease: Immunological Findings in Three Patients and Proposal of a Unifying Pathogenic Hypothesis"],"prefix":"10.3389","volume":"10","author":[{"given":"Edoardo","family":"Errichiello","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efthimios","family":"Dardiotis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiorenza","family":"Mannino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juha","family":"Paloneva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Mattina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orsetta","family":"Zuffardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2019,7,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1212\/WNL.56.11.1552","article-title":"CNS manifestations of Nasu-Hakola disease: a frontal dementia with bone cysts","volume":"56","author":"Paloneva","year":"2001","journal-title":"Neurology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1086\/342259","article-title":"Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype","volume":"71","author":"Paloneva","year":"2002","journal-title":"Am J Hum Genet"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1502","DOI":"10.1212\/01.WNL.0000160304.00003.CA","article-title":"The genetic causes of basal ganglia calcification, dementia, and bone cysts: DAP12 and TREM2","volume":"64","author":"Kl\u00fcnemann","year":"2005","journal-title":"Neurology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.neurobiolaging.2013.09.009","article-title":"Investigating the role of rare heterozygous TREM2 variants in Alzheimer's disease and frontotemporal dementia","volume":"35","author":"Cuyvers","year":"2014","journal-title":"Neurobiol Aging"},{"key":"B5","doi-asserted-by":"publisher","first-page":"4931","DOI":"10.1007\/s12035-015-9416-7","article-title":"Convergent genetic and expression datasets highlight TREM2 in Parkinson's disease susceptibility","volume":"53","author":"Liu","year":"2016","journal-title":"Mol Neurobiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"e257","DOI":"10.1212\/NXG.0000000000000257","article-title":"Association study between multiple system atrophy and TREM2 p.R47H","volume":"4","author":"Ogaki","year":"2018","journal-title":"Neurol Genet"},{"key":"B7","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1016\/j.immuni.2017.08.008","article-title":"The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases","volume":"47","author":"Krasemann","year":"2017","journal-title":"Immunity"},{"key":"B8","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/77153","article-title":"Loss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with bone cysts","volume":"25","author":"Paloneva","year":"2000","journal-title":"Nat Genet"},{"key":"B9","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1111\/j.1600-065X.2009.00841.x","article-title":"The expanding roles of ITAM adapters FcRgamma and DAP12 in myeloid cells","volume":"232","author":"Hamerman","year":"2009","journal-title":"Immunol Rev"},{"key":"B10","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.bcmd.2017.03.002","article-title":"Whole exome sequencing in the differential diagnosis of Diamond-Blackfan anemia: clinical and molecular study of three patients with novel RPL5 and mosaic RPS19 mutations","volume":"64","author":"Errichiello","year":"2017","journal-title":"Blood Cells Mol Dis."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1111\/j.1468-1331.2010.03311.x","article-title":"Nasu-Hakola disease with a splicing mutation of TREM2 in a Japanese family","volume":"18","author":"Numasawa","year":"2011","journal-title":"Eur J Neurol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"194.e13","DOI":"10.1016\/j.neurobiolaging.2017.01.015","article-title":"A novel mutation in TREM2 gene causing Nasu-Hakola disease and review of the literature","volume":"53","author":"Dardiotis","year":"2017","journal-title":"Neurobiol Aging"},{"key":"B13","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1038\/nri1106","article-title":"TREMs in the immune system and beyond","volume":"3","author":"Colonna","year":"2003","journal-title":"Nat Rev Immunol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1670","DOI":"10.1002\/eji.200425932","article-title":"KARAP\/DAP12\/TYROBP: three names and a multiplicity of biological functions","volume":"35","author":"Tomasello","year":"2005","journal-title":"Eur J Immunol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.3389\/fimmu.2018.01121","article-title":"Triggering receptors expressed on myeloid cells 2 promotes corneal resistance against pseudomonas aeruginosa by inhibiting caspase-1-dependent pyroptosis","volume":"9","author":"Qu","year":"2018","journal-title":"Front Immunol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"2587","DOI":"10.4049\/jimmunol.1400326","article-title":"Quantitative reduction of the TCR adapter protein SLP-76 unbalances immunity and immune regulation","volume":"194","author":"Siggs","year":"2015","journal-title":"J Immunol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1038\/ncb1416","article-title":"Plexin-A1 and its interaction with DAP12 in immune responses and bone homeostasis","volume":"8","author":"Takegahara","year":"2006","journal-title":"Nat Cell Biol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"E7917","DOI":"10.1073\/pnas.1612717113","article-title":"MIF allele-dependent regulation of the MIF coreceptor CD44 and role in rheumatoid arthritis","volume":"113","author":"Yoo","year":"2016","journal-title":"Proc Natl Acad Sci USA."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1111\/ijd.13344","article-title":"Evaluation of macrophage migration inhibitory factor (MIF) levels in serum and lesional skin of patients with alopecia areata","volume":"55","author":"Salem","year":"2016","journal-title":"Int J Dermatol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"e110073","DOI":"10.1371\/journal.pone.0110073","article-title":"Proteomic analysis of lymphoblastoid cells from Nasu-Hakola patients: a step forward in our understanding of this neurodegenerative disorder","volume":"9","author":"Giuliano","year":"2014","journal-title":"PLoS ONE."},{"key":"B21","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1038\/nrgastro.2013.101","article-title":"Autoimmune atrophic gastritis\u2013pathogenesis, pathology and management","volume":"10","author":"Neumann","year":"2013","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.coi.2017.11.003","article-title":"Natural killer cell education in human health and disease","volume":"50","author":"Boudreau","year":"2018","journal-title":"Curr Opin Immunol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1111\/imr.12725","article-title":"Emerging insights into human health and NK cell biology from the study of NK cell deficiencies","volume":"287","author":"Mace","year":"2019","journal-title":"Immunol Rev."},{"key":"B24","doi-asserted-by":"publisher","first-page":"2669","DOI":"10.1182\/blood-2012-09-453969","article-title":"Mutations in GATA2 cause human NK cell deficiency with specific loss of the CD56(bright) subset","volume":"121","author":"Mace","year":"2013","journal-title":"Blood."},{"key":"B25","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1172\/JCI61014","article-title":"Partial MCM4 deficiency in patients with growth retardation, adrenal insufficiency, and natural killer cell deficiency","volume":"122","author":"Gineau","year":"2012","journal-title":"J Clin Invest"},{"key":"B26","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1172\/JCI60224","article-title":"MCM4 mutation causes adrenal failure, short stature, and natural killer cell deficiency in humans","volume":"122","author":"Hughes","year":"2012","journal-title":"J Clin Invest"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1016\/j.jaci.2015.04.021","article-title":"A homozygous mutation of RTEL1 in a child presenting with an apparently isolated natural killer cell deficiency","volume":"136","author":"Hanna","year":"2015","journal-title":"J Allergy Clin Immunol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1991","DOI":"10.1172\/JCI90727","article-title":"Inherited GINS1 deficiency underlies growth retardation along with neutropenia and NK cell deficiency","volume":"127","author":"Cottineau","year":"2017","journal-title":"J Clin Invest."},{"key":"B29","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1172\/JCI86276","article-title":"Biallelic mutations in IRF8 impair human NK cell maturation and function","volume":"127","author":"Mace","year":"2017","journal-title":"J Clin Invest."},{"key":"B30","doi-asserted-by":"publisher","first-page":"3769","DOI":"10.1172\/JCI64837","article-title":"Human immunodeficiency-causing mutation defines CD16 in spontaneous NK cell cytotoxicity","volume":"122","author":"Grier","year":"2012","journal-title":"J Clin Invest"},{"key":"B31","doi-asserted-by":"publisher","first-page":"413","DOI":"10.3233\/JAD-161277","article-title":"Higher peripheral TREM2 mRNA levels relate to cognitive deficits and hippocampal atrophy in Alzheimer's disease and amnestic mild cognitive impairment","volume":"58","author":"Tan","year":"2017","journal-title":"J Alzheimers Dis"},{"key":"B32","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1111\/ene.13583","article-title":"Increased expression of TREM2 in peripheral cells from mild cognitive impairment patients who progress into Alzheimer's disease","volume":"25","author":"Casati","year":"2018","journal-title":"Eur J Neurol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.cyto.2018.12.024","article-title":"Inflammatory expression profile in peripheral blood mononuclear cells from patients with Nasu-Hakola Disease","volume":"116","author":"Galimberti","year":"2019","journal-title":"Cytokine"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1016\/j.cell.2018.05.003","article-title":"Disease-associated microglia: a universal immune sensor of neurodegeneration","volume":"173","author":"Deczkowska","year":"2018","journal-title":"Cell."},{"key":"B35","doi-asserted-by":"publisher","first-page":"6937","DOI":"10.1038\/s41598-018-25204-2","article-title":"Small nuclear RNA-mediated modulation of splicing reveals a therapeutic strategy for a TREM2 mutation and its post-transcriptional regulation","volume":"8","author":"Yanaizu","year":"2018","journal-title":"Sci Rep."}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2019.01685\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T00:42:03Z","timestamp":1563842523000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2019.01685\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,23]]},"references-count":35,"alternative-id":["10.3389\/fimmu.2019.01685"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2019.01685","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,23]]},"article-number":"1685"}}