{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T21:00:03Z","timestamp":1793826003575,"version":"4.6.1"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2020,7,7]],"date-time":"2020-07-07T00:00:00Z","timestamp":1594080000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,7,7]],"date-time":"2020-07-07T00:00:00Z","timestamp":1594080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFG SFB1160, TPA01"],"award-info":[{"award-number":["DFG SFB1160, TPA01"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01EO1303"],"award-info":[{"award-number":["01EO1303"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007311","name":"Deutsche Kinderkrebsstiftung","doi-asserted-by":"publisher","award":["DKS 2016.04 and DKS 2018.11"],"award-info":[{"award-number":["DKS 2016.04 and DKS 2018.11"]}],"id":[{"id":"10.13039\/501100007311","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Pediatric Immunology Research Chair, Bank of Montreal"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Clin Immunol"],"published-print":{"date-parts":[[2020,8]]},"DOI":"10.1007\/s10875-020-00814-6","type":"journal-article","created":{"date-parts":[[2020,7,7]],"date-time":"2020-07-07T22:02:27Z","timestamp":1594159347000},"page":"901-916","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":85,"title":["Neuroinflammatory Disease as an Isolated Manifestation of Hemophagocytic Lymphohistiocytosis"],"prefix":"10.1007","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1150-6133","authenticated-orcid":false,"given":"Annaliesse","family":"Blincoe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Heeg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick K.","family":"Campbell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Hines","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amer","family":"Khojah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa","family":"Klein-Gitelman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie-An","family":"Talano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Speckmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabien","family":"Touzot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjan","family":"Lankester","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geertje E.","family":"Legger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques G.","family":"Rivi\u00e8re","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Garcia-Prat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Alonso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria C.","family":"Putti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Lehmberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Maier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmine","family":"El Chazli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa Abd","family":"Elmaksoud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itziar","family":"Astigarraga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalja","family":"Kurjane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inita","family":"Bulina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktorija","family":"Kenina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yenan","family":"Bryceson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Rascon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Lortie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gal","family":"Goldstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Booth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austen","family":"Worth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangeline","family":"Wassmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica G.","family":"Schmitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia T.","family":"Warren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey J.","family":"Bednarski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salah","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuang-Yueh","family":"Chiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joerg","family":"Krueger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael M.","family":"Henry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M.","family":"Holland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca A.","family":"Marsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Ehl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elie","family":"Haddad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,7]]},"reference":[{"issue":"7","key":"814_CR1","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/s41582-018-0024-9","volume":"14","author":"E Wells","year":"2018","unstructured":"Wells E, Hacohen Y, Waldman A, Tillema JM, Soldatos A, Ances B, et al. Neuroimmune disorders of the central nervous system in children in the molecular era. Nat Rev Neurol. 2018;14(7):433\u201345.","journal-title":"Nat Rev Neurol"},{"issue":"1","key":"814_CR2","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1182\/blood-2017-11-814244","volume":"132","author":"IK Chinn","year":"2018","unstructured":"Chinn IK, Eckstein OS, Peckham-Gregory EC, Goldberg BR, Forbes LR, Nicholas SK, et al. Genetic and mechanistic diversity in pediatric hemophagocytic lymphohistiocytosis. Blood. 2018;132(1):89\u2013100.","journal-title":"Blood."},{"issue":"4","key":"814_CR3","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.blre.2014.03.002","volume":"28","author":"GE Janka","year":"2014","unstructured":"Janka GE, Lehmberg K. Hemophagocytic syndromes\u2014an update. Blood Rev. 2014;28(4):135\u201342.","journal-title":"Blood Rev"},{"issue":"1","key":"814_CR4","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1111\/j.0105-2896.2010.00890.x","volume":"235","author":"JP Schmid","year":"2010","unstructured":"Schmid JP, C\u00f4te M, M\u00e9nager MM, Burgess A, Nehme N, M\u00e9nasch\u00e9 G, et al. Inherited defects in lymphocyte cytotoxic activity. Immunol Rev. 2010;235(1):10\u201323.","journal-title":"Immunol Rev"},{"issue":"2","key":"814_CR5","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1002\/pbc.21039","volume":"48","author":"J-I Henter","year":"2007","unstructured":"Henter J-I, Horne A, Aric\u00f3 M, Egeler RM, Filipovich AH, Imashuku S, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48(2):124\u201331.","journal-title":"Pediatr Blood Cancer"},{"issue":"3","key":"814_CR6","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1182\/blood.V89.3.794","volume":"89","author":"E Haddad","year":"1997","unstructured":"Haddad E, Sulis M-L, Jabado N, Blanche S, Fischer A, Tardieu M. Frequency and severity of central nervous system lesions in hemophagocytic lymphohistiocytosis. Blood. 1997;89(3):794\u2013800.","journal-title":"Blood."},{"issue":"3","key":"814_CR7","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1111\/j.1365-2141.2007.06922.x","volume":"140","author":"A Horne","year":"2008","unstructured":"Horne A, Trottestam H, Aric\u00f2 M, Egeler RM, Filipovich AH, Gadner H, et al. Frequency and spectrum of central nervous system involvement in 193 children with haemophagocytic lymphohistiocytosis. Br J Haematol. 2008;140(3):327\u201335.","journal-title":"Br J Haematol"},{"issue":"5","key":"814_CR8","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1016\/j.jaip.2018.05.031","volume":"6","author":"S Ehl","year":"2018","unstructured":"Ehl S, Astigarraga I, von Bahr GT, Hines M, Horne A, Ishii E, et al. Recommendations for the use of etoposide-based therapy and bone marrow transplantation for the treatment of HLH: consensus statements by the HLH Steering Committee of the Histiocyte Society. J Allergy Clin Immunol Pract. 2018;6(5):1508\u201317.","journal-title":"J Allergy Clin Immunol Pract"},{"issue":"22","key":"814_CR9","doi-asserted-by":"crossref","first-page":"5794","DOI":"10.1182\/blood-2011-07-370148","volume":"118","author":"K Zhang","year":"2011","unstructured":"Zhang K, Jordan MB, Marsh RA, Johnson JA, Kissell D, Meller J, et al. Hypomorphic mutations in PRF1, MUNC13-4, and STXBP2 are associated with adult-onset familial HLH. Blood. 2011;118(22):5794\u20138.","journal-title":"Blood."},{"issue":"7","key":"814_CR10","doi-asserted-by":"crossref","first-page":"2658","DOI":"10.1182\/blood-2004-09-3590","volume":"105","author":"J Feldmann","year":"2005","unstructured":"Feldmann J. Severe and progressive encephalitis as a presenting manifestation of a novel missense perforin mutation and impaired cytolytic activity. Blood. 2005;105(7):2658\u201363.","journal-title":"Blood."},{"issue":"11","key":"814_CR11","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1038\/ejhg.2013.20","volume":"21","author":"C Dias","year":"2013","unstructured":"Dias C, McDonald A, Sincan M, Rupps R, Markello T, Salvarinova R, et al. Recurrent subacute post-viral onset of ataxia associated with a PRF1 mutation. Eur J Hum Genet. 2013;21(11):1232\u20139.","journal-title":"Eur J Hum Genet"},{"issue":"3","key":"814_CR12","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/s10072-010-0467-2","volume":"32","author":"L Chiapparini","year":"2011","unstructured":"Chiapparini L, Uziel G, Vallinoto C, Bruzzone MG, Rovelli A, Tricomi G, et al. Hemophagocytic lymphohistiocytosis with neurological presentation: MRI findings and a nearly miss diagnosis. Neurol Sci. 2011;32(3):473\u20137.","journal-title":"Neurol Sci"},{"issue":"5","key":"814_CR13","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1002\/pbc.21438","volume":"50","author":"AD Beaty","year":"2008","unstructured":"Beaty AD, Weller C, Levy B, Vogler C, Ferguson WS, Bicknese A, et al. A teenage boy with late onset hemophagocytic lymphohistiocytosis with predominant neurologic disease and perforin deficiency. Pediatr Blood Cancer. 2008;50(5):1070\u20132.","journal-title":"Pediatr Blood Cancer"},{"issue":"12","key":"814_CR14","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.1002\/pbc.25646","volume":"62","author":"B Tesi","year":"2015","unstructured":"Tesi B, Chiang SCC, El-Ghoneimy D, Hussein AA, Langenski\u00f6ld C, Wali R, et al. Spectrum of atypical clinical presentations in patients with biallelic PRF1 missense mutations. Pediatr Blood Cancer. 2015;62(12):2094\u2013100.","journal-title":"Pediatr Blood Cancer"},{"issue":"22","key":"814_CR15","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1212\/WNL.0000000000002729","volume":"86","author":"C Murphy","year":"2016","unstructured":"Murphy C, Nanthapisal S, Gilmour K, Laurent S, D'Arco F, Hemingway C, et al. Progressive neurologic disorder: initial manifestation of hemophagocytic lymphohistiocytosis. Neurology. 2016;86(22):2109\u201311.","journal-title":"Neurology."},{"issue":"3","key":"814_CR16","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1002\/art.22442","volume":"56","author":"D Moshous","year":"2007","unstructured":"Moshous D, Feyen O, Lankisch P, Schwarz K, Schaper J, Schneider M, et al. Primary necrotizing lymphocytic central nervous system vasculitis due to perforin deficiency in a four-year-old girl. Arthritis Rheum. 2007;56(3):995\u20139.","journal-title":"Arthritis Rheum"},{"issue":"12","key":"814_CR17","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1093\/jnen\/nly094","volume":"77","author":"IH Solomon","year":"2018","unstructured":"Solomon IH, Li H, Benson LA, Henderson LA, Degar BA, Gorman MP, et al. Histopathologic correlates of familial hemophagocytic lymphohistiocytosis isolated to the central nervous system. J Neuropathol Exp Neurol. 2018;77(12):1079\u201384.","journal-title":"J Neuropathol Exp Neurol"},{"issue":"4","key":"814_CR18","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1182\/bloodadvances.2018027417","volume":"3","author":"H Li","year":"2019","unstructured":"Li H, Benson LA, Henderson LA, Solomon IH, Kennedy AL, Soldatos A, et al. Central nervous system-restricted familial hemophagocytic lymphohistiocytosis responds to hematopoietic cell transplantation. Blood Adv. 2019;3(4):503\u20137.","journal-title":"Blood Adv"},{"issue":"4","key":"814_CR19","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1111\/bjd.14866","volume":"176","author":"JYW Lee","year":"2017","unstructured":"Lee JYW, Eldeeb MS, Hsu CK, Saito R, Abouzeid SA, McGrath JA. Further evidence for genotype-phenotype disparity in Griscelli syndrome. Br J Dermatol. 2017;176(4):1086\u20139.","journal-title":"Br J Dermatol"},{"key":"814_CR20","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.msard.2018.07.031","volume":"25","author":"H Algahtani","year":"2018","unstructured":"Algahtani H, Absi A, Bassuni W, Shirah B. Adult-onset hemophagocytic lymphohistiocytosis type 2 presenting as a demyelinating disease. Mult Scler Relat Disord. 2018;25:77\u201382.","journal-title":"Mult Scler Relat Disord"},{"issue":"1","key":"814_CR21","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.jaci.2018.02.031","volume":"142","author":"B Tesi","year":"2018","unstructured":"Tesi B, Rascon J, Chiang SCC, Burnyte B, L\u00f6fstedt A, Fasth A, et al. A RAB27A 5\u2032 untranslated region structural variant associated with late-onset hemophagocytic lymphohistiocytosis and normal pigmentation. J Allergy Clin Immunol. 2018;142(1):317\u201321.e8.","journal-title":"J Allergy Clin Immunol"},{"issue":"1","key":"814_CR22","doi-asserted-by":"crossref","first-page":"e13101","DOI":"10.1111\/petr.13101","volume":"22","author":"S Khazal","year":"2017","unstructured":"Khazal S, Polishchuk V, Soffer G, Prinzing S, Gill J, Mahadeo KM. Allogeneic hematopoietic stem cell transplantation is associated with cure and durable remission of late-onset primary isolated central nervous system hemophagocytic lymphohistiocytosis. Pediatr Transplant. 2017;22(1):e13101.","journal-title":"Pediatr Transplant"},{"issue":"12","key":"814_CR23","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.3324\/haematol.2010.029389","volume":"95","author":"J Rohr","year":"2010","unstructured":"Rohr J, Beutel K, Maul-Pavicic A, Vraetz T, Thiel J, Warnatz K, et al. Atypical familial hemophagocytic lymphohistiocytosis due to mutations in UNC13D and STXBP2 overlaps with primary immunodeficiency diseases. Haematologica. 2010;95(12):2080\u20137.","journal-title":"Haematologica."},{"issue":"1","key":"814_CR24","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1146\/annurev-med-041610-134208","volume":"63","author":"GE Janka","year":"2012","unstructured":"Janka GE. Familial and acquired hemophagocytic lymphohistiocytosis. Annu Rev Med. 2012;63(1):233\u201346.","journal-title":"Annu Rev Med"},{"issue":"1","key":"814_CR25","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s11940-017-0439-4","volume":"19","author":"A Horne","year":"2017","unstructured":"Horne A, Wickstr\u00f6m R, Jordan MB, Yeh EA, Naqvi A, Henter J-I, et al. How to treat involvement of the central nervous system in hemophagocytic lymphohistiocytosis? Curr Treat Options Neurol. 2017;19(1):3.","journal-title":"Curr Treat Options Neurol"},{"issue":"15","key":"814_CR26","doi-asserted-by":"crossref","first-page":"4041","DOI":"10.1182\/blood-2011-03-278127","volume":"118","author":"MB Jordan","year":"2011","unstructured":"Jordan MB, Allen CE, Weitzman S, Filipovich AH, McClain KL. How I treat hemophagocytic lymphohistiocytosis. Blood. 2011;118(15):4041\u201352.","journal-title":"Blood."},{"issue":"7","key":"814_CR27","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1177\/0883073807304203","volume":"22","author":"LC Turtzo","year":"2007","unstructured":"Turtzo LC, Lin DDM, Hartung H, Barker PB, Arceci R, Yohay K. A neurologic presentation of familial hemophagocytic lymphohistiocytosis which mimicked septic emboli to the brain. J Child Neurol. 2007;22(7):863\u20138.","journal-title":"J Child Neurol"},{"issue":"08","key":"814_CR28","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1017\/S0012162201001001","volume":"43","author":"M Kieslich","year":"2001","unstructured":"Kieslich M, Vecchi M, Driever PH, Laverda AM, Schwabe D, Jacobi G. Acute encephalopathy as a primary manifestation of haemophagocytic lymphohistiocytosis. Dev Med Child Neurol. 2001;43(08):555.","journal-title":"Dev Med Child Neurol"},{"issue":"6","key":"814_CR29","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1007\/s00247-003-0894-9","volume":"33","author":"NE Fitzgerald","year":"2003","unstructured":"Fitzgerald NE, MacClain KL. Imaging characteristics of hemophagocytic lymphohistiocytosis. Pediatr Radiol. 2003;33(6):392\u2013401.","journal-title":"Pediatr Radiol"},{"issue":"6","key":"814_CR30","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1016\/j.clinimag.2015.07.013","volume":"39","author":"TL Anderson","year":"2015","unstructured":"Anderson TL, Carr CM, Kaufmann TJ. Central nervous system imaging findings of hemophagocytic syndrome. Clin Imaging. 2015;39(6):1090\u20134.","journal-title":"Clin Imaging"},{"issue":"1","key":"814_CR31","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s00381-009-0957-9","volume":"26","author":"N Decaminada","year":"2009","unstructured":"Decaminada N, Cappellini M, Mortilla M, Del Giudice E, Sieni E, Caselli D, et al. Familial hemophagocytic lymphohistiocytosis: clinical and neuroradiological findings and review of the literature. Childs Nerv Syst. 2009;26(1):121\u20137.","journal-title":"Childs Nerv Syst"},{"issue":"11","key":"814_CR32","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1007\/s00247-007-0569-z","volume":"37","author":"HW Goo","year":"2007","unstructured":"Goo HW, Weon YC. A spectrum of neuroradiological findings in children with haemophagocytic lymphohistiocytosis. Pediatr Radiol. 2007;37(11):1110\u20137.","journal-title":"Pediatr Radiol"},{"issue":"5","key":"814_CR33","doi-asserted-by":"crossref","first-page":"e636","DOI":"10.1542\/peds.111.5.e636","volume":"111","author":"L Rooms","year":"2003","unstructured":"Rooms L, Fitzgerald N, McClain KL. Hemophagocytic lymphohistiocytosis masquerading as child abuse: presentation of three cases and review of central nervous system findings in hemophagocytic lymphohistiocytosis. Pediatrics. 2003;111(5):e636\u2013e40.","journal-title":"Pediatrics"},{"key":"814_CR34","doi-asserted-by":"crossref","first-page":"101452","DOI":"10.1016\/j.msard.2019.101452","volume":"37","author":"P Wildner","year":"2020","unstructured":"Wildner P, Stasio\u0142ek M, Matysiak M. Differential diagnosis of multiple sclerosis and other inflammatory CNS diseases. Mult Scler Relat Disord. 2020;37:101452.","journal-title":"Mult Scler Relat Disord"},{"issue":"12","key":"814_CR35","doi-asserted-by":"crossref","first-page":"2754","DOI":"10.1182\/blood-2011-08-374199","volume":"119","author":"YT Bryceson","year":"2012","unstructured":"Bryceson YT, Pende D, Maul-Pavicic A, Gilmour KC, Ufheil H, Vraetz T, et al. A prospective evaluation of degranulation assays in the rapid diagnosis of familial hemophagocytic syndromes. Blood. 2012;119(12):2754\u201363.","journal-title":"Blood."},{"issue":"8","key":"814_CR36","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1007\/s10875-017-0443-1","volume":"37","author":"S Ammann","year":"2017","unstructured":"Ammann S, Lehmberg K, zur Stadt U, Klemann C, SFN B, Speckmann C, et al. Effective immunological guidance of genetic analyses including exome sequencing in patients evaluated for hemophagocytic lymphohistiocytosis. J Clin Immunol. 2017;37(8):770\u201380.","journal-title":"J Clin Immunol"},{"issue":"4","key":"814_CR37","doi-asserted-by":"crossref","first-page":"538","DOI":"10.3324\/haematol.2009.019562","volume":"95","author":"V Cetica","year":"2010","unstructured":"Cetica V, Pende D, Griffiths GM, Aric\u00f2 M. Molecular basis of familial hemophagocytic lymphohistiocytosis. Haematologica. 2010;95(4):538\u201341.","journal-title":"Haematologica."},{"issue":"7","key":"814_CR38","doi-asserted-by":"crossref","first-page":"978","DOI":"10.3324\/haematol.11233","volume":"92","author":"K Nagafuji","year":"2007","unstructured":"Nagafuji K, Nonami A, Kumano T, Kikushige Y, Yoshimoto G, Takenaka K, et al. Perforin gene mutations in adult-onset hemophagocytic lymphohistiocytosis. Haematologica. 2007;92(7):978\u201381.","journal-title":"Haematologica."},{"issue":"2","key":"814_CR39","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1097\/MPH.0000000000000597","volume":"39","author":"M Madkaikar","year":"2017","unstructured":"Madkaikar M, Gupta M, Dixit A, Patil V. Predominant neurologic manifestations seen in a patient with a biallelic perforin1 mutation (PRF1; p.R225W). J Pediatr Hematol Oncol. 2017;39(2):143\u20136.","journal-title":"J Pediatr Hematol Oncol"},{"issue":"1","key":"814_CR40","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.jaci.2015.06.048","volume":"137","author":"V Cetica","year":"2016","unstructured":"Cetica V, Sieni E, Pende D, Danesino C, De Fusco C, Locatelli F, et al. Genetic predisposition to hemophagocytic lymphohistiocytosis: report on 500 patients from the Italian registry. J Allergy Clin Immunol. 2016;137(1):188\u201396.e4.","journal-title":"J Allergy Clin Immunol"},{"issue":"1","key":"814_CR41","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1136\/jmg.2007.052670","volume":"45","author":"A Trizzino","year":"2007","unstructured":"Trizzino A, Stadt U, Ueda I, Risma K, Janka G, Ishii E, et al. Genotype phenotype study of familial haemophagocytic lymphohistiocytosis due to perforin mutations. J Med Genet. 2007;45(1):15\u201321.","journal-title":"J Med Genet"},{"issue":"5","key":"814_CR42","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1136\/jmg.2010.085456","volume":"48","author":"E Sieni","year":"2011","unstructured":"Sieni E, Cetica V, Santoro A, Beutel K, Mastrodicasa E, Meeths M, et al. Genotype-phenotype study of familial haemophagocytic lymphohistiocytosis type 3. J Med Genet. 2011;48(5):343\u201352.","journal-title":"J Med Genet"},{"issue":"10","key":"814_CR43","doi-asserted-by":"crossref","first-page":"6786","DOI":"10.4049\/jimmunol.180.10.6786","volume":"180","author":"C Pivot-Pajot","year":"2008","unstructured":"Pivot-Pajot C, Varoqueaux F, de Saint BG, Bourgoin SG. Munc13-4 regulates granule secretion in human neutrophils. J Immunol. 2008;180(10):6786\u201397.","journal-title":"J Immunol"},{"issue":"19","key":"814_CR44","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1182\/bloodadvances.2017007526","volume":"1","author":"L Broglie","year":"2017","unstructured":"Broglie L, Pommert L, Rao S, Thakar M, Phelan R, Margolis D, et al. Ruxolitinib for treatment of refractory hemophagocytic lymphohistiocytosis. Blood Adv. 2017;1(19):1533\u20136.","journal-title":"Blood Adv"},{"issue":"1","key":"814_CR45","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1182\/blood-2016-02-700013","volume":"128","author":"S Maschalidi","year":"2016","unstructured":"Maschalidi S, Sepulveda FE, Garrigue A, Fischer A, de Saint Basile G. Therapeutic effect of JAK1\/2 blockade on the manifestations of hemophagocytic lymphohistiocytosis in mice. Blood. 2016;128(1):60\u201371.","journal-title":"Blood."},{"issue":"13","key":"814_CR46","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1182\/blood-2015-12-684399","volume":"127","author":"R Das","year":"2016","unstructured":"Das R, Guan P, Sprague L, Verbist K, Tedrick P, An QA, et al. Janus kinase inhibition lessens inflammation and ameliorates disease in murine models of hemophagocytic lymphohistiocytosis. Blood. 2016;127(13):1666\u201375.","journal-title":"Blood."},{"issue":"3","key":"814_CR47","doi-asserted-by":"crossref","first-page":"e560","DOI":"10.1212\/NXI.0000000000000560","volume":"6","author":"LA Benson","year":"2019","unstructured":"Benson LA, Li H, Henderson LA, Solomon IH, Soldatos A, Murphy J, et al. Pediatric CNS-isolated hemophagocytic lymphohistiocytosis. Neurol Neuroimmunol Neuroinflamm. 2019;6(3):e560\u2013e.","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"issue":"3","key":"814_CR48","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.pediatrneurol.2013.10.014","volume":"50","author":"A Jovanovic","year":"2014","unstructured":"Jovanovic A, Kuzmanovic M, Kravljanac R, Micic D, Jovic M, Gazikalovic S, et al. Central nervous system involvement in hemophagocytic lymphohistiocytosis: a single-center experience. Pediatr Neurol. 2014;50(3):233\u20137.","journal-title":"Pediatr Neurol"},{"issue":"15","key":"814_CR49","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1212\/WNL.0b013e31824f800a","volume":"78","author":"K Deiva","year":"2012","unstructured":"Deiva K, Mahlaoui N, Beaudonnet F, de Saint BG, Caridade G, Moshous D, et al. CNS involvement at the onset of primary hemophagocytic lymphohistiocytosis. Neurology. 2012;78(15):1150\u20136.","journal-title":"Neurology."},{"issue":"6","key":"814_CR50","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1172\/JCI43157","volume":"121","author":"EM Behrens","year":"2011","unstructured":"Behrens EM, Canna SW, Slade K, Rao S, Kreiger PA, Paessler M, et al. Repeated TLR9 stimulation results in macrophage activation syndrome-like disease in mice. J Clin Invest. 2011;121(6):2264\u201377.","journal-title":"J Clin Invest"},{"issue":"11","key":"814_CR51","doi-asserted-by":"crossref","DOI":"10.1002\/pbc.27344","volume":"65","author":"M Heeg","year":"2018","unstructured":"Heeg M, Ammann S, Klemann C, Panning M, Falcone V, Hengel H, et al. Is an infectious trigger always required for primary hemophagocytic lymphohistiocytosis? Lessons from in utero and neonatal disease. Pediatr Blood Cancer. 2018;65(11):e27344.","journal-title":"Pediatr Blood Cancer"},{"issue":"22","key":"814_CR52","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.1182\/blood-2016-12-753830","volume":"129","author":"TS Rubin","year":"2017","unstructured":"Rubin TS, Zhang K, Gifford C, Lane A, Choo S, Bleesing JJ, et al. Perforin and CD107a testing is superior to NK cell function testing for screening patients for genetic HLH. Blood. 2017;129(22):2993\u20139.","journal-title":"Blood."}],"container-title":["Journal of Clinical Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10875-020-00814-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10875-020-00814-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10875-020-00814-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T23:40:53Z","timestamp":1625614853000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10875-020-00814-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,7]]},"references-count":52,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,8]]}},"alternative-id":["814"],"URL":"https:\/\/doi.org\/10.1007\/s10875-020-00814-6","relation":{},"ISSN":["0271-9142","1573-2592"],"issn-type":[{"value":"0271-9142","type":"print"},{"value":"1573-2592","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,7]]},"assertion":[{"value":"27 March 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 June 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study was approved by the ethics committee of the University of Freiburg (EK No. 159\/19).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standards"}},{"value":"SE was part of an Advisory Board at UCB and has received research support from UCB. EH is a consultant for Leadiant. KL is part of an Advisory Board at SOBI. AL is member of the advisory board at Neovii and has received research support from Medac. The remaining authors declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}}]}}