{"entity": "researcher", "timestamp": "2026-08-10T10:31:38.983Z", "family": "Norlin", "given": "Anna Carin", "initials": "AC", "orcid": "0000-0001-5503-1689", "affiliations": ["Immunodeficiency Unit, Infectious Disease Clinic, Karolinska University Hospital, Stockholm, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/3c0fe142669148538fd228de442b87a2.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/3c0fe142669148538fd228de442b87a2"}}, "publications": [{"entity": "publication", "iuid": "b9461e2dab3c45d891518478219868dd", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b9461e2dab3c45d891518478219868dd.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b9461e2dab3c45d891518478219868dd"}}, "title": "Three Adult Cases of STAT1 Gain-of-Function with Chronic Mucocutaneous Candidiasis Treated with JAK Inhibitors.", "authors": [{"family": "Borgstr\u00f6m", "given": "Emilie W", "initials": "EW", "orcid": "0000-0002-4269-5475", "researcher": {"href": "https://publications.scilifelab.se/researcher/4833a08012f642b098ba90c88ae74e3d.json"}}, {"family": "Edvinsson", "given": "Marie", "initials": "M"}, {"family": "P\u00e9rez", "given": "Luc\u00eda P", "initials": "LP"}, {"family": "Norlin", "given": "Anna C", "initials": "AC", "orcid": "0000-0001-5503-1689", "researcher": {"href": "https://publications.scilifelab.se/researcher/3c0fe142669148538fd228de442b87a2.json"}}, {"family": "Enoksson", "given": "Sara L", "initials": "SL"}, {"family": "Hansen", "given": "Susanne", "initials": "S"}, {"family": "Fasth", "given": "Anders", "initials": "A", "orcid": "0000-0002-0033-740X", "researcher": {"href": "https://publications.scilifelab.se/researcher/57576e445b0844f287e58d868dd22574.json"}}, {"family": "Friman", "given": "Vanda", "initials": "V"}, {"family": "K\u00e4mpe", "given": "Olle", "initials": "O", "orcid": "0000-0001-6091-9914", "researcher": {"href": "https://publications.scilifelab.se/researcher/2c547dc809a14cdaa47b623cf638162b.json"}}, {"family": "M\u00e5nsson", "given": "Robert", "initials": "R", "orcid": "0000-0003-0738-0328", "researcher": {"href": "https://publications.scilifelab.se/researcher/eafa5ad22891454298bf31a94d77175f.json"}}, {"family": "Estupi\u00f1\u00e1n", "given": "Hernando Y", "initials": "HY"}, {"family": "Wang", "given": "Qing", "initials": "Q"}, {"family": "Ziyang", "given": "Tan", "initials": "T"}, {"family": "Lakshmikanth", "given": "Tadepally", "initials": "T", "orcid": "0000-0001-7256-5770", "researcher": {"href": "https://publications.scilifelab.se/researcher/92e81aa6b0cf4ff0a18b14098bf0fcc1.json"}}, {"family": "Smith", "given": "Carl Inge E", "initials": "CIE", "orcid": "0000-0003-1907-3392", "researcher": {"href": "https://publications.scilifelab.se/researcher/b3ea998a87b44c218f91701cf3019af1.json"}}, {"family": "Brodin", "given": "Petter", "initials": "P", "orcid": "0000-0002-8103-0046", "researcher": {"href": "https://publications.scilifelab.se/researcher/40097353cdb24e52bf2330eb687042bf.json"}}, {"family": "Bergman", "given": "Peter", "initials": "P", "orcid": "0000-0003-3306-3713", "researcher": {"href": "https://publications.scilifelab.se/researcher/397d11713c80456bb600b1e4c88ff843.json"}}], "type": "journal article", "published": "2023-01-00", "journal": {"title": "J Clin Immunol", "issn": "1573-2592", "volume": "43", "issue": "1", "pages": "136-150", "issn-l": "0271-9142"}, "abstract": "The aim of this study was to characterize clinical effects and biomarkers in three patients with chronic mucocutaneous candidiasis (CMC) caused by gain-of-function (GOF) mutations in the STAT1 gene during treatment with Janus kinase (JAK) inhibitors.\n\nMass cytometry (CyTOF) was used to characterize mononuclear leukocyte populations and Olink assay to quantify 265 plasma proteins. Flow-cytometric Assay for Specific Cell-mediated Immune-response in Activated whole blood (FASCIA) was used to quantify the reactivity against Candida albicans.\n\nOverall, JAK inhibitors improved clinical symptoms of CMC, but caused side effects in two patients. Absolute numbers of neutrophils, T cells, B cells, and NK cells were sustained during baricitinib treatment. Detailed analysis of cellular subsets, using CyTOF, revealed increased expression of CD45, CD52, and CD99 in NK cells, reflecting a more functional phenotype. Conversely, monocytes and eosinophils downregulated CD16, consistent with reduced inflammation. Moreover, T and B cells showed increased expression of activation markers during treatment. In one patient with a remarkable clinical effect of baricitinib treatment, the immune response to C. albicans increased after 7 weeks of treatment. Alterations in plasma biomarkers involved downregulation of cellular markers CXCL10, annexin A1, granzyme B, granzyme H, and oncostatin M, whereas FGF21 was the only upregulated marker after 7 weeks. After 3 months, IFN-\u0263 and CXCL10 were downregulated.\n\nThe clinical effect of JAK inhibitor treatment of CMC is promising. Several biological variables were altered during baricitinib treatment demonstrating that lymphocytes, NK cells, monocytes, and eosinophils were affected. In parallel, cellular reactivity against C. albicans was enhanced.", "doi": "10.1007/s10875-022-01351-0", "pmid": "36050429", "labels": {"Cellular Immunomonitoring": "Collaborative", "Clinical Genomics Stockholm": "Service", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9840596"}, {"db": "pii", "key": "10.1007/s10875-022-01351-0"}], "notes": [], "created": "2022-09-04T08:15:08.566Z", "modified": "2024-01-16T13:48:34.251Z"}, {"entity": "publication", "iuid": "bce3eb78ee8e4437bf9e297ccb44a8f7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bce3eb78ee8e4437bf9e297ccb44a8f7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bce3eb78ee8e4437bf9e297ccb44a8f7"}}, "title": "X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19.", "authors": [{"family": "Asano", "given": "Takaki", "initials": "T", "orcid": "0000-0003-1424-2433", "researcher": {"href": "https://publications.scilifelab.se/researcher/ac5194017554453e88b16a4db83ff29a.json"}}, {"family": "Boisson", "given": "Bertrand", "initials": "B", "orcid": "0000-0001-5240-3555", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7c47acbcc3346bcb65102b534b25cc8.json"}}, {"family": "Onodi", "given": "Fanny", "initials": "F", "orcid": "0000-0002-8429-4821", "researcher": {"href": "https://publications.scilifelab.se/researcher/734764c2e1a24c1c88b6de07fee9c1d2.json"}}, {"family": "Matuozzo", "given": "Daniela", "initials": "D", "orcid": "0000-0001-9514-3837", "researcher": {"href": "https://publications.scilifelab.se/researcher/3a74128c36fa425981d8f14b0dc7e90e.json"}}, {"family": "Moncada-Velez", "given": "Marcela", "initials": "M", "orcid": "0000-0002-3073-5345", "researcher": {"href": "https://publications.scilifelab.se/researcher/2bf242c5e03d4aec82e164cc56a45bc8.json"}}, {"family": "Maglorius Renkilaraj", "given": 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"researcher": {"href": "https://publications.scilifelab.se/researcher/4f748eaca6cf4a1e92a420cb8a81f9e4.json"}}, {"family": "Ozcelik", "given": "Tayfun", "initials": "T"}, {"family": "Novelli", "given": "Giuseppe", "initials": "G", "orcid": "0000-0002-7781-602X", "researcher": {"href": "https://publications.scilifelab.se/researcher/d6a6a7759bc043c399af7995628c531d.json"}}, {"family": "Novelli", "given": "Antonio", "initials": "A"}, {"family": "Casari", "given": "Giorgio", "initials": "G", "orcid": "0000-0002-0115-8980", "researcher": {"href": "https://publications.scilifelab.se/researcher/05d55d03f73c4f5fa28bb7feb16d3eb5.json"}}, {"family": "Aiuti", "given": "Alessandro", "initials": "A", "orcid": "0000-0002-5398-1717", "researcher": {"href": "https://publications.scilifelab.se/researcher/cf293cf031a549f2bdc073608988c01a.json"}}, {"family": "Carrera", "given": "Paola", "initials": "P"}, {"family": "Bondesan", "given": "Simone", "initials": "S", "orcid": "0000-0003-4367-8623", 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"https://publications.scilifelab.se/researcher/24ef4ca1eb3a4b1bbee73f07cd64fe92.json"}}, {"family": "Su", "given": "Helen C", "initials": "HC", "orcid": "0000-0002-5582-9110", "researcher": {"href": "https://publications.scilifelab.se/researcher/5f3b00f2707541b39b2205d70fd2d6f7.json"}}, {"family": "Jouanguy", "given": "Emmanuelle", "initials": "E", "orcid": "0000-0002-7358-9157", "researcher": {"href": "https://publications.scilifelab.se/researcher/2667361dc2e7417bb94bfc89bf425cc6.json"}}, {"family": "Amara", "given": "Ali", "initials": "A"}, {"family": "Soumelis", "given": "Vassili", "initials": "V", "orcid": "0000-0003-1849-9834", "researcher": {"href": "https://publications.scilifelab.se/researcher/140bfa7d989d40419b80967ea524e390.json"}}, {"family": "Cobat", "given": "Aur\u00e9lie", "initials": "A", "orcid": "0000-0001-7209-6257", "researcher": {"href": "https://publications.scilifelab.se/researcher/eaba2f9452294eec89161b589d96ff29.json"}}, {"family": "Zhang", "given": "Qian", "initials": "Q", "orcid": "0000-0002-9040-3289", "researcher": {"href": "https://publications.scilifelab.se/researcher/5bee352280384ad99b180f4f4bac42f5.json"}}, {"family": "Casanova", "given": "Jean-Laurent", "initials": "JL", "orcid": "0000-0002-7782-4169", "researcher": {"href": "https://publications.scilifelab.se/researcher/009e2306468648c08fb1eea319f0c488.json"}}], "type": "journal article", "published": "2021-08-19", "journal": {"title": "Sci Immunol", "issn": "2470-9468", "volume": "6", "issue": "62", "issn-l": null}, "abstract": "Autosomal inborn errors of type I IFN immunity and autoantibodies against these cytokines underlie at least 10% of critical COVID-19 pneumonia cases. We report very rare, biochemically deleterious X-linked TLR7 variants in 16 unrelated male individuals aged 7 to 71 years (mean: 36.7 years) from a cohort of 1,202 male patients aged 0.5 to 99 years (mean: 52.9 years) with unexplained critical COVID-19 pneumonia. None of the 331 asymptomatically or mildly infected male individuals aged 1.3 to 102 years (mean: 38.7 years) tested carry such TLR7 variants (p = 3.5 \u00d7 10-5). The phenotypes of five hemizygous relatives of index cases infected with SARS-CoV-2 include asymptomatic or mild infection (n=2, 5 and 38 years), or moderate (n=1, 5 years), severe (n=1, 27 years), or critical (n=1, 29 years) pneumonia. Two boys (aged 7 and 12 years) from a cohort of 262 male patients with severe COVID-19 pneumonia (mean: 51.0 years) are hemizygous for a deleterious TLR7 variant. The cumulative allele frequency for deleterious TLR7 variants in the male general population is < 6.5x10-4 We also show that blood B cell lines and myeloid cell subsets from the patients do not respond to TLR7 stimulation, a phenotype rescued by wild-type TLR7 The patients' blood plasmacytoid dendritic cells (pDCs) produce low levels of type I IFNs in response to SARS-CoV-2. Overall, X-linked recessive TLR7 deficiency is a highly penetrant genetic etiology of critical COVID-19 pneumonia, in about 1.8% of male patients below the age of 60 years. Human TLR7 and pDCs are essential for protective type I IFN immunity against SARS-CoV-2 in the respiratory tract.", "doi": "10.1126/sciimmunol.abl4348", "pmid": "34413140", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "mid", "key": "NIHMS1744435"}, {"db": "pmc", "key": "PMC8532080"}, {"db": "pii", "key": "6/62/eabl4348"}], "notes": [], "created": "2022-11-30T05:59:36.974Z", "modified": "2023-06-19T09:15:18.018Z"}]}