{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T19:50:36Z","timestamp":1793130636222,"version":"4.5.0"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T00:00:00Z","timestamp":1724803200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T00:00:00Z","timestamp":1724803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Clin Immunol"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hereditary C1q deficiency (C1QDef) is a rare monogenic disorder leading to defective complement pathway activation and systemic lupus erythematosus (SLE)-like manifestations. The link between impairment of the complement cascade and autoimmunity remains incompletely understood. Here, we assessed type 1 interferon pathway activation in patients with C1QDef. Twelve patients with genetically confirmed C1QDef were recruited through an international collaboration. Clinical, biological and radiological data were collected retrospectively. The expression of a standardized panel of interferon stimulated genes (ISGs) in peripheral blood was measured, and the level of interferon alpha (IFN\u03b1) protein in cerebrospinal fluid (CSF) determined using SIMOA technology. Central nervous system (encompassing basal ganglia calcification, encephalitis, vasculitis, chronic pachymeningitis), mucocutaneous and renal involvement were present, respectively, in 10, 11 and 2 of 12 patients, and severe infections recorded in 2\/12 patients. Elevated ISG expression was observed in all patients tested (<jats:italic>n<\/jats:italic>\u2009=\u200910\/10), and serum and CSF IFN\u03b1 elevated in 2\/2 patients. Three patients were treated with Janus-kinase inhibitors (JAKi), with variable outcome; one displaying an apparently favourable response in respect of cutaneous and neurological features, and two others experiencing persistent disease despite JAKi therapy. To our knowledge, we report the largest original series of genetically confirmed C1QDef yet described. Additionally, we present a review of all previously described genetically confirmed cases of C1QDef. Overall, individuals with C1QDef demonstrate many characteristics of recognized monogenic interferonopathies: particularly, cutaneous involvement (malar rash, acral vasculitic\/papular rash, chilblains), SLE-like disease, basal ganglia calcification, increased expression of ISGs in peripheral blood, and elevated levels of CSF IFN\u03b1.\n<\/jats:p>","DOI":"10.1007\/s10875-024-01788-5","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T07:02:29Z","timestamp":1724828549000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Hereditary C1q Deficiency is Associated with Type 1 Interferon-Pathway Activation and a High Risk of Central Nervous System Inflammation"],"prefix":"10.1007","volume":"44","author":[{"given":"Cl\u00e9ment","family":"Triaille","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neha Mohan","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian I.","family":"Rice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Seabra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fraser J. H.","family":"Sutherland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Bondet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darragh","family":"Duffy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew R.","family":"Gennery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Fournier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Bader-Meunier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Troedson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin","family":"Cleary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Buso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Dalby-Payne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prajakta","family":"Ranade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrien","family":"Jansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lien","family":"De Somer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Louise","family":"Fr\u00e9mond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pallavi Pimpale","family":"Chavan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell C.","family":"Dale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carine","family":"Wouters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Quartier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raju","family":"Khubchandani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanick J.","family":"Crow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,28]]},"reference":[{"issue":"1","key":"1788_CR1","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.molimm.2015.03.007","volume":"67","author":"M Stegert","year":"2015","unstructured":"Stegert M, Bock M, Trendelenburg M. Clinical presentation of human C1q deficiency: How much of a lupus? Mol Immunol. 2015;67(1):3\u201311.","journal-title":"Mol Immunol"},{"key":"1788_CR2","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.jaut.2015.06.002","volume":"62","author":"RA van Schaarenburg","year":"2015","unstructured":"van Schaarenburg RA, Schejbel L, Truedsson L, Topaloglu R, Al-Mayouf SM, Riordan A, et al. Marked variability in clinical presentation and outcome of patients with C1q immunodeficiency. J Autoimmun. 2015;62:39\u201344.","journal-title":"J Autoimmun"},{"key":"1788_CR3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2022.102979","volume":"137","author":"SL Coss","year":"2023","unstructured":"Coss SL, Zhou D, Chua GT, Aziz RA, Hoffman RP, Wu YL, et al. The complement system and human autoimmune diseases. J Autoimmun. 2023;137: 102979.","journal-title":"J Autoimmun"},{"issue":"8","key":"1788_CR4","doi-asserted-by":"publisher","first-page":"4738","DOI":"10.4049\/jimmunol.1001731","volume":"185","author":"DM Santer","year":"2010","unstructured":"Santer DM, Hall BE, George TC, Tangsombatvisit S, Liu CL, Arkwright PD, et al. C1q deficiency leads to the defective suppression of IFN-alpha in response to nucleoprotein containing immune complexes. J Immunol. 2010;185(8):4738\u201349.","journal-title":"J Immunol"},{"issue":"3","key":"1788_CR5","first-page":"678","volume":"62","author":"O Meyer","year":"1985","unstructured":"Meyer O, Hauptmann G, Tappeiner G, Ochs HD, Mascart-Lemone F. Genetic deficiency of C4, C2 or C1q and lupus syndromes. Association with anti-Ro (SS-A) antibodies. 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The complement system in systemic lupus erythematosus: an update. Ann Rheum Dis. 2014;73(9):1601\u20136.","journal-title":"Ann Rheum Dis"},{"issue":"6388","key":"1788_CR9","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1126\/science.aao4555","volume":"360","author":"GS Ling","year":"2018","unstructured":"Ling GS, Crawford G, Buang N, Bartok I, Tian K, Thielens NM, et al. C1q restrains autoimmunity and viral infection by regulating CD8(+) T cell metabolism. Science. 2018;360(6388):558\u201363.","journal-title":"Science"},{"issue":"10","key":"1788_CR10","doi-asserted-by":"publisher","first-page":"3081","DOI":"10.1002\/art.24852","volume":"60","author":"C Lood","year":"2009","unstructured":"Lood C, Gullstrand B, Truedsson L, Olin AI, Alm GV, Ronnblom L, et al. C1q inhibits immune complex-induced interferon-alpha production in plasmacytoid dendritic cells: a novel link between C1q deficiency and systemic lupus erythematosus pathogenesis. Arthritis Rheum. 2009;60(10):3081\u201390.","journal-title":"Arthritis Rheum"},{"issue":"8","key":"1788_CR11","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1038\/s41577-021-00633-9","volume":"22","author":"YJ Crow","year":"2022","unstructured":"Crow YJ, Stetson DB. The type I interferonopathies: 10 years on. Nat Rev Immunol. 2022;22(8):471\u201383.","journal-title":"Nat Rev Immunol"},{"issue":"6","key":"1788_CR12","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1177\/0961203313486950","volume":"22","author":"C Troedson","year":"2013","unstructured":"Troedson C, Wong M, Dalby-Payne J, Wilson M, Dexter M, Rice GI, et al. Systemic lupus erythematosus due to C1q deficiency with progressive encephalopathy, intracranial calcification and acquired moyamoya cerebral vasculopathy. 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Int J Hematol. 2021;113(2):302\u20137.","journal-title":"Int J Hematol"},{"issue":"6","key":"1788_CR23","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.1097\/TP.0000000000000975","volume":"100","author":"RF Olsson","year":"2016","unstructured":"Olsson RF, Hagelberg S, Schiller B, Ringden O, Truedsson L, Ahlin A. Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of Human C1q Deficiency: The Karolinska Experience. Transplantation. 2016;100(6):1356\u201362.","journal-title":"Transplantation"},{"issue":"1","key":"1788_CR24","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/j.jaci.2013.07.035","volume":"133","author":"PD Arkwright","year":"2014","unstructured":"Arkwright PD, Riley P, Hughes SM, Alachkar H, Wynn RF. Successful cure of C1q deficiency in human subjects treated with hematopoietic stem cell transplantation. J Allergy Clin Immunol. 2014;133(1):265\u20137.","journal-title":"J Allergy Clin Immunol"},{"issue":"6","key":"1788_CR25","doi-asserted-by":"publisher","first-page":"1439","DOI":"10.1016\/j.jaci.2020.04.002","volume":"146","author":"C Wolf","year":"2020","unstructured":"Wolf C, Bruck N, Koss S, Griep C, Kirschfink M, Palm-Beden K, et al. Janus kinase inhibition in complement component 1 deficiency. J Allergy Clin Immunol. 2020;146(6):1439-42 e5.","journal-title":"J Allergy Clin Immunol."}],"container-title":["Journal of Clinical Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10875-024-01788-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10875-024-01788-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10875-024-01788-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T04:42:54Z","timestamp":1730436174000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10875-024-01788-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,28]]},"references-count":25,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["1788"],"URL":"https:\/\/doi.org\/10.1007\/s10875-024-01788-5","relation":{},"ISSN":["0271-9142","1573-2592"],"issn-type":[{"value":"0271-9142","type":"print"},{"value":"1573-2592","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,28]]},"assertion":[{"value":"5 March 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 August 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 August 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by the Comit\u00e9 de Protection des Personnes (ID-RCB\/EUDRACT: 2014-A01017-40) and the Leeds (East) Research Ethics Committee (10\/H1307\/132).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Samples were obtained from the probands and\/or parents\/guardians as appropriate with written informed consent.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"185"}}