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Three Adult Cases o...
Three Adult Cases of STAT1 Gain-of-Function with Chronic Mucocutaneous Candidiasis Treated with JAK Inhibitors
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- Borgström, Emilie W. (author)
- Karolinska Institutet
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- Edvinsson, Marie (author)
- Uppsala universitet,Infektionsmedicin
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- Perez, Lucia P. (author)
- Karolinska Institutet
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- Norlin, Anna C. (author)
- Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Clin Immunol & Transfus Med, Stockholm, Sweden.
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- Enoksson, Sara L. (author)
- Karolinska Univ Hosp, Dept Clin Immunol & Transfus Med, Stockholm, Sweden.
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- Hansen, Susanne (author)
- Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden.
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- Fasth, Anders, 1945 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Clinical Sciences, Department of Pediatrics
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- Friman, Vanda, 1952 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine
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- Kämpe, Olle (author)
- Karolinska Inst, Dept Med, Expt Endocrinol, Stockholm, Sweden.
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- Månsson, Robert (author)
- Karolinska Institutet
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- Estupinan, Hernando Y. (author)
- Karolinska Institutet
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Wang, Qing (author)
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Ziyang, Tan (author)
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- Lakshmikanth, Tadepally (author)
- Karolinska Institutet
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- Smith, Carl Inge E. (author)
- Karolinska Institutet
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- Brodin, Petter (author)
- Karolinska Institutet
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- Bergman, Peter (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2022-09-02
- 2023
- English.
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In: Journal of Clinical Immunology. - : Springer. - 0271-9142 .- 1573-2592. ; 43, s. 136-150
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Abstract
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- Purpose; 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.Methods: Mass 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.Results: Overall, 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-gamma and CXCL10 were downregulated.Conclusions: The 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Keyword
- JAK inhibitor
- chronic mucocutaneous candidiasis
- STAT1
- mass cytometry
- Olink
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Borgström, Emili ...
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Edvinsson, Marie
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Perez, Lucia P.
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Norlin, Anna C.
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Enoksson, Sara L ...
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Hansen, Susanne
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Fasth, Anders, 1 ...
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Friman, Vanda, 1 ...
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Kämpe, Olle
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Månsson, Robert
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Estupinan, Herna ...
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Wang, Qing
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Ziyang, Tan
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Lakshmikanth, Ta ...
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Smith, Carl Inge ...
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Brodin, Petter
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Bergman, Peter
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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Journal of Clini ...
- By the university
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Uppsala University
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Karolinska Institutet
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University of Gothenburg