{"entity": "researcher", "timestamp": "2026-05-21T04:27:19.864Z", "family": "Fasth", "given": "Anders", "initials": "A", "orcid": "0000-0002-0033-740X", "affiliations": ["Department of Paediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/57576e445b0844f287e58d868dd22574.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/57576e445b0844f287e58d868dd22574"}}, "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": "60bd85765d1d41e8a85dc1c7ff43bbfc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/60bd85765d1d41e8a85dc1c7ff43bbfc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/60bd85765d1d41e8a85dc1c7ff43bbfc"}}, "title": "Long-Term Follow-Up of Newborns with 22q11 Deletion Syndrome and Low TRECs", "authors": [{"family": "Framme", "given": "Jenny Lingman", "initials": "JL", "orcid": "0000-0001-5665-1927", "researcher": {"href": "https://publications.scilifelab.se/researcher/adf94743f00c47fa98def118f68b791a.json"}}, {"family": "Lundqvist", "given": "Christina", "initials": "C", "orcid": "0000-0002-2256-4072", "researcher": {"href": "https://publications.scilifelab.se/researcher/10b339e6cc1f48f3a5f736201038ee59.json"}}, {"family": "Lundell", "given": "Anna Carin", "initials": "AC"}, {"family": "van Schouwenburg", "given": "Pauline A", "initials": "PA"}, {"family": "Lemarquis", "given": "Andri L", "initials": "AL", "orcid": "0000-0001-5165-0247", "researcher": {"href": "https://publications.scilifelab.se/researcher/776e9a2ecebf446ba4d0e3d20c8d793c.json"}}, {"family": "Th\u00f6rn", "given": "Karolina", "initials": "K"}, {"family": "Lindgren", "given": "Susanne", "initials": "S"}, {"family": "Gudmundsdottir", "given": "Judith", "initials": "J", "orcid": "0000-0002-4500-4078", "researcher": {"href": "https://publications.scilifelab.se/researcher/cd10ee75400d497a8d1c5b9ac7fccdc7.json"}}, {"family": "Lundberg", "given": "Vanja", "initials": "V"}, {"family": "Degerman", "given": "Sofie", "initials": "S", "orcid": "0000-0002-2783-0712", "researcher": {"href": "https://publications.scilifelab.se/researcher/8611162e883645f59195c4221199967f.json"}}, {"family": "Zetterstr\u00f6m", "given": "Rolf H", "initials": "RH"}, {"family": "Borte", "given": "Stephan", "initials": "S"}, {"family": "Hammarstr\u00f6m", "given": "Lennart", "initials": "L", "orcid": "0000-0002-8635-9609", "researcher": {"href": "https://publications.scilifelab.se/researcher/542d61d71652421f8dda0f0154fe063b.json"}}, {"family": "Telemo", "given": "Esbj\u00f6rn", "initials": "E"}, {"family": "Hultdin", "given": "Magnus", "initials": "M"}, {"family": "van der Burg", "given": "Mirjam", "initials": "M"}, {"family": "Fasth", "given": "Anders", "initials": "A", "orcid": "0000-0002-0033-740X", "researcher": {"href": "https://publications.scilifelab.se/researcher/57576e445b0844f287e58d868dd22574.json"}}, {"family": "Oskarsd\u00f3ttir", "given": "S\u00f3lveig", "initials": "S"}, {"family": "Ekwall", "given": "Olov", "initials": "O", "orcid": "0000-0002-4506-9955", "researcher": {"href": "https://publications.scilifelab.se/researcher/2d7af11d7d30410d8fe5f3b5fbd0ba1d.json"}}], "type": "journal-article", "published": "2022-04-00", "journal": {"title": "J Clin Immunol", "issn": "0271-9142", "volume": "42", "issue": "3", "pages": "618-633", "issn-l": null}, "abstract": "Population-based neonatal screening using T-cell receptor excision circles (TRECs) identifies infants with profound T lymphopenia, as seen in cases of severe combined immunodeficiency, and in a subgroup of infants with 22q11 deletion syndrome (22q11DS).\n\nTo investigate the long-term prognostic value of low levels of TRECs in newborns with 22q11DS.\n\nSubjects with 22q11DS and low TRECs at birth (22q11Low, N=10), matched subjects with 22q11DS and normal TRECs (22q11Normal, N=10), and matched healthy controls (HC, N=10) were identified. At follow-up (median age 16 years), clinical and immunological characterizations, covering lymphocyte subsets, immunoglobulins, TRECs, T-cell receptor repertoires, and relative telomere length (RTL) measurements were performed.\n\nAt follow-up, the 22q11Low group had lower numbers of na\u00efve T-helper cells, na\u00efve T-regulatory cells, na\u00efve cytotoxic T cells, and persistently lower TRECs compared to healthy controls. Receptor repertoires showed skewed V-gene usage for na\u00efve T-helper cells, whereas for na\u00efve cytotoxic T cells, shorter RTL and a trend towards higher clonality were found. Multivariate discriminant analysis revealed a clear distinction between the three groups and a skewing towards Th17 differentiation of T-helper cells, particularly in the 22q11Low individuals. Perturbations of B-cell subsets were found in both the 22q11Low and 22q11Normal group compared to the HC group, with larger proportions of na\u00efve B cells and lower levels of memory B cells, including switched memory B cells.\n\nThis long-term follow-up study shows that 22q11Low individuals have persistent immunologic aberrations and increased risk for immune dysregulation, indicating the necessity of lifelong monitoring.\n\nThis study elucidates the natural history of childhood immune function in newborns with 22q11DS and low TRECs, which may facilitate the development of programs for long-term monitoring and therapeutic choices.", "doi": "10.1007/s10875-021-01201-5", "pmid": "35080750", "labels": {"Clinical Genomics Ume\u00e5": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9016018"}, {"db": "pii", "key": "10.1007/s10875-021-01201-5"}], "notes": [], "created": "2022-12-05T11:19:16.118Z", "modified": "2023-06-19T11:54:31.135Z"}, {"entity": "publication", "iuid": "f125e73101d940caba08bd49d0ba39d9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f125e73101d940caba08bd49d0ba39d9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f125e73101d940caba08bd49d0ba39d9"}}, "title": "Eleven percent intact PGM3 in a severely immunodeficient patient with a novel splice-site mutation, a case report", "authors": [{"family": "Lundin", "given": "Karin E", "initials": "KE", "orcid": "0000-0002-1489-3028", "researcher": {"href": "https://publications.scilifelab.se/researcher/84ba7b3018604f2a8c63927f163bd527.json"}}, {"family": "Wang", "given": "Qing", "initials": "Q"}, {"family": "Hamasy", "given": "Abdulrahman", "initials": "A"}, {"family": "Marits", "given": "Per", "initials": "P", "orcid": "0000-0003-2439-5687", "researcher": {"href": "https://publications.scilifelab.se/researcher/b05d944415ab42bca1b696262176dfc0.json"}}, {"family": "Uzunel", "given": "Mehmet", "initials": "M"}, {"family": "Wirta", "given": "Valtteri", "initials": "V", "orcid": "0000-0003-3811-5439", "researcher": {"href": "https://publications.scilifelab.se/researcher/cba024b2e3c347f6b981922d984ad2d6.json"}}, {"family": "Wikstr\u00f6m", "given": "Ann Charlotte", "initials": "AC"}, {"family": "Fasth", "given": "Anders", "initials": "A", "orcid": "0000-0002-0033-740X", "researcher": {"href": "https://publications.scilifelab.se/researcher/57576e445b0844f287e58d868dd22574.json"}}, {"family": "Ekwall", "given": "Olov", "initials": "O", "orcid": "0000-0002-4506-9955", "researcher": {"href": "https://publications.scilifelab.se/researcher/2d7af11d7d30410d8fe5f3b5fbd0ba1d.json"}}, {"family": "Smith", "given": "C I Edvard", "initials": "CIE", "orcid": "0000-0003-1907-3392", "researcher": {"href": "https://publications.scilifelab.se/researcher/b3ea998a87b44c218f91701cf3019af1.json"}}], "type": "journal-article", "published": "2018-12-00", "journal": {"volume": "18", "issn": "1471-2431", "issue": "1", "pages": "285", "title": "BMC Pediatr", "issn-l": "1471-2431"}, "abstract": "A novel immunodeficiency, frequently accompanied by high serum-IgE, and caused by mutations in the PGM3 gene was described in 2014. To date there are no unique phenotype characteristics for PGM3 deficiency. PGM3 encodes a carbohydrate-modifying enzyme, phosphoglucomutase 3. Null-mutations are quite likely lethal, and to date only missense mutations or small deletions have been reported. Such mutations frequently cause a combination of reduced enzyme activity and protein instability, complicating determination of the enzyme level needed for survival. Here we present the first patient with a homozygous splice-modifying mutation in the PGM3 gene. An A > G substitution at position c.871 + 3 (transcript NM_001199917) is causing a deletion of exon 7 in the majority of PGM3 transcripts. In addition, this case further increases the clinical phenotypes of immunodeficiency caused by PGM3 mutations.\n\nWe describe the symptoms of a 3-year-old girl who was severely growth retarded, had vascular malformations, extensive eczema, multiple food-allergies, and was prone to infections. Unlike the majority of reported PGM3 deficient patients she lacked skeletal dysplasia and had normal neurocognitive development. In addition to the high serum-IgE, she displayed altered T cell numbers with reduced na\u00efve CD4+ and CD8+ T-cells, increased number of activated effector memory CD8+ T cells and aberrant T-cell functions. The patient was homozygous for a new hypomorphic, splice-modifying mutation in the PGM3 gene, causing severely reduced mRNA levels. In the patient's cells, we observed 5% intact mRNA and approximately 11% of the protein levels seen in healthy controls. Treatment with allogeneic hematopoietic stem cell therapy was planned, but unfortunately the clinical condition deteriorated with multi-organ failure, which led to her death at 3 years of age.\n\nThere is still no specific phenotype identified that distinguishes immunodeficiency caused by PGM3 mutations from other forms of immunodeficiency. The patient described here yields new information on the phenotypic variability among these patients. In addition, since all the synthesized protein is wild-type, it is possible for the first time to estimate the enzyme activity in vivo. The results suggest that1/10 of the normal PGM3 level is sufficient for survival but that it is insufficient for accurate carbohydrate processing.", "doi": "10.1186/s12887-018-1258-9", "pmid": "30157810", "labels": {"Clinical Genomics Stockholm": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC6114780"}, {"db": "pii", "key": "10.1186/s12887-018-1258-9"}], "notes": [], "created": "2018-10-29T09:09:50.653Z", "modified": "2023-06-19T11:21:14.962Z"}]}