ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Villarino AV, Kanno Y, O’Shea JJ, 2017. Mechanisms and consequences of Jak-STAT signaling in the immune system. Nat Immunol 18: 374–384.
-
2.
Hu X, Li J, Fu M, Zhao X, Wang W, 2021. The JAK/STAT signaling pathway: From bench to clinic. Signal Transduct Target Ther 6: 402.
-
3.
Zhang W, Chen X, Gao G, Xing S, Zhou L, Tang X, Zhao X, An Y, 2021. Clinical relevance of gain- and loss-of-function germline mutations in STAT1: A systematic review. Front Immunol 12: 654406.
-
4.
Bernasconi AR, Yancoski J, Villa M, Oleastro MM, Galicchio M, Rossi JG, 2018. Increased STAT1 amounts correlate with the phospho-STAT1 level in STAT1 gain-of-function defects. J Clin Immunol 38: 745–747.
-
5.
Boehmer DFR, et al., 2020. A novel complete autosomal-recessive STAT1 LOF variant causes immunodeficiency with hemophagocytic lymphohistiocytosis-like hyperinflammation. J Allergy Clin Immunol Pract 8: 3102–3111.
-
6.
Scott O, Lindsay K, Erwood S, Mollica A, Roifman CM, Cohn RD, Ivakine EA, 2021. STAT1 gain-of-function heterozygous cell models reveal diverse interferon-signature gene transcriptional responses. NPJ Genom Med 6: 34.
-
7.
Le Voyer T, et al., 2021. Genetic, immunological, and clinical features of 32 patients with autosomal recessive STAT1 deficiency. J Immunol 207: 133–152.
-
8.
Bezerra-Santos M, et al., 2018. Mycobacterium leprae recombinant antigen induces high expression of multifunction T lymphocytes and is promising as a specific vaccine for leprosy. Front Immunol 9: 2920.
-
9.
Santos CNO, Caldas GC, de Oliveira FA, da Silva AM, da Silva JS, da Silva RLL, de Jesus AR, Magalhães LS, de Almeida RP, 2023. COVID-19 recurrence is related to disease-early profile T cells while detection of anti-S1 IgG is related to multifunctional T cells. Med Microbiol Immunol (Berl) 212: 339–347.
-
10.
Magalhães LS, et al., 2022. Use of N-acetylcysteine as treatment adjuvant regulates immune response in visceral leishmaniasis: Pilot clinical trial and in vitro experiments. Front Cell Infect Microbiol 12: 1045668.
-
11.
Okada S, Asano T, Moriya K, Boisson-Dupuis S, Kobayashi M, Casanova J-L, Puel A, 2020. Human STAT1 gain-of-function heterozygous mutations: Chronic mucocutaneous candidiasis and type I interferonopathy. J Clin Immunol 40: 1065–1081.
-
12.
Toubiana J, et al., 2016. Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype. Blood 127: 3154–3164.
-
13.
Borgström EW, et al., 2022. Three adult cases of STAT1 gain-of-function with chronic mucocutaneous candidiasis treated with JAK inhibitors. J Clin Immunol 43: 136–150.
-
14.
Sampaio EP, et al., 2012. A novel STAT1 mutation associated with disseminated mycobacterial disease. J Clin Immunol 32: 681–689.
-
15.
Kataoka S, et al., 2016. Extrapulmonary tuberculosis mimicking Mendelian susceptibility to mycobacterial disease in a patient with signal transducer and activator of transcription 1 (STAT1) gain-of-function mutation. J Allergy Clin Immunol 137: 619–622.e1.
-
16.
Lyra PT, Falcão ACAM, Cruz RA, Coelho AVC, Souza EDS, Alencar LCA, Oliveira JB, 2022. Gain-of-function STAT1 mutation and visceral leishmaniasis. Einstein (São Paulo) 20: eRC0048.
-
17.
Fujiki R, Hijikata A, Shirai T, Okada S, Kobayashi M, Ohara O, 2017. Molecular mechanism and structural basis of gain-of-function of STAT1 caused by pathogenic R274Q mutation. J Biol Chem 292: 6240–6254.
-
18.
Yamazaki Y, et al., 2014. Two novel gain-of-function mutations of STAT1 responsible for chronic mucocutaneous candidiasis disease: Impaired production of IL-17A and IL-22, and the presence of anti–IL-17F autoantibody. J Immunol 193: 4880–4887.
-
19.
Zimmerman O, et al., 2019. STAT1 gain-of-function mutations cause high total STAT1 levels with normal dephosphorylation. Front Immunol 10: 1433.
-
20.
Parackova Z, Zentsova I, Vrabcova P, Sediva A, Bloomfield M, 2023. Aberrant tolerogenic functions and proinflammatory skew of dendritic cells in STAT1 gain-of-function patients may contribute to autoimmunity and fungal susceptibility. Clin Immunol 246: 109174.
-
21.
Parackova Z, Vrabcova P, Zentsova I, Sediva A, Bloomfield M, 2023. Neutrophils in STAT1 gain-of-function have a pro-inflammatory signature which is not rescued by JAK inhibition. J Clin Immunol 43: 1640–1659.
-
22.
Tamaura M, et al., 2020. Human gain-of-function STAT1 mutation disturbs IL-17 immunity in mice. Int Immunol 32: 259–272.
-
23.
Ling Y, et al., 2015. Inherited IL-17RC deficiency in patients with chronic mucocutaneous candidiasis. J Exp Med 212: 619.
-
24.
Liu L, et al., 2011. Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis. J Exp Med 208: 1635–1648.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 638 | 638 | 509 |
| Full Text Views | 22 | 22 | 13 |
| PDF Downloads | 32 | 32 | 18 |
Coinfection of Leprosy and Chronic Mucocutaneous Candidiasis in a Family with STAT1 Gain-of-Function Mutation
Lais Lima de Oliveira Rekowski
Lais Lima de Oliveira Rekowski
Laboratory of Immunology and Molecular Biology, Federal University of Sergipe, Aracaju, Brazil;
Health Sciences Graduate Program, Federal University of Sergipe, Aracaju, Brazil;
Search for other papers by Lais Lima de Oliveira Rekowski in
Current site
Google Scholar
PubMed
Health Sciences Graduate Program, Federal University of Sergipe, Aracaju, Brazil;
Search for other papers by Lais Lima de Oliveira Rekowski in
Current site
Google Scholar
PubMed
Gustavo Costa Caldas
Gustavo Costa Caldas
Laboratory of Immunology and Molecular Biology, Federal University of Sergipe, Aracaju, Brazil;
Department of Medicine, University Hospital, Federal University of Sergipe, Aracaju, Brazil;
Search for other papers by Gustavo Costa Caldas in
Current site
Google Scholar
PubMed
Department of Medicine, University Hospital, Federal University of Sergipe, Aracaju, Brazil;
Search for other papers by Gustavo Costa Caldas in
Current site
Google Scholar
PubMed
Lucas Menezes-Silva
Lucas Menezes-Silva
Department of Medicine, University Hospital, Federal University of Sergipe, Aracaju, Brazil;
Search for other papers by Lucas Menezes-Silva in
Current site
Google Scholar
PubMed
Search for other papers by Lucas Menezes-Silva in
Current site
Google Scholar
PubMed
Camilla Natália Oliveira Santos
Camilla Natália Oliveira Santos
Laboratory of Immunology and Molecular Biology, Federal University of Sergipe, Aracaju, Brazil;
Health Sciences Graduate Program, Federal University of Sergipe, Aracaju, Brazil;
Search for other papers by Camilla Natália Oliveira Santos in
Current site
Google Scholar
PubMed
Health Sciences Graduate Program, Federal University of Sergipe, Aracaju, Brazil;
Search for other papers by Camilla Natália Oliveira Santos in
Current site
Google Scholar
PubMed
Lucas Sousa Magalhães
lucas.smagalhaes@hotmail.com
Lucas Sousa Magalhães
Laboratory of Immunology and Molecular Biology, Federal University of Sergipe, Aracaju, Brazil;
Institute of Biological and Health Sciences, Federal University of Alagoas, Maceió, Brazil;
Search for other papers by Lucas Sousa Magalhães in
Current site
Google Scholar
PubMed
Institute of Biological and Health Sciences, Federal University of Alagoas, Maceió, Brazil;
Search for other papers by Lucas Sousa Magalhães in
Current site
Google Scholar
PubMed
Rodrigo Anselmo Cazzaniga
Rodrigo Anselmo Cazzaniga
Laboratory of Immunology and Molecular Biology, Federal University of Sergipe, Aracaju, Brazil;
Search for other papers by Rodrigo Anselmo Cazzaniga in
Current site
Google Scholar
PubMed
Search for other papers by Rodrigo Anselmo Cazzaniga in
Current site
Google Scholar
PubMed
Nailson Alves dos Santos
Nailson Alves dos Santos
Department of Medicine, University Hospital, Federal University of Sergipe, Aracaju, Brazil;
Search for other papers by Nailson Alves dos Santos in
Current site
Google Scholar
PubMed
Search for other papers by Nailson Alves dos Santos in
Current site
Google Scholar
PubMed
Priscila Lima Santos
Priscila Lima Santos
Laboratory of Immunology and Molecular Biology, Federal University of Sergipe, Aracaju, Brazil;
Health Sciences Graduate Program, Federal University of Sergipe, Aracaju, Brazil;
Search for other papers by Priscila Lima Santos in
Current site
Google Scholar
PubMed
Health Sciences Graduate Program, Federal University of Sergipe, Aracaju, Brazil;
Search for other papers by Priscila Lima Santos in
Current site
Google Scholar
PubMed
Ricardo Luís Louzada da Silva
Ricardo Luís Louzada da Silva
Laboratory of Immunology and Molecular Biology, Federal University of Sergipe, Aracaju, Brazil;
Search for other papers by Ricardo Luís Louzada da Silva in
Current site
Google Scholar
PubMed
Search for other papers by Ricardo Luís Louzada da Silva in
Current site
Google Scholar
PubMed
Angela Maria da Silva
Angela Maria da Silva
Laboratory of Immunology and Molecular Biology, Federal University of Sergipe, Aracaju, Brazil;
Health Sciences Graduate Program, Federal University of Sergipe, Aracaju, Brazil;
Department of Medicine, University Hospital, Federal University of Sergipe, Aracaju, Brazil;
Search for other papers by Angela Maria da Silva in
Current site
Google Scholar
PubMed
Health Sciences Graduate Program, Federal University of Sergipe, Aracaju, Brazil;
Department of Medicine, University Hospital, Federal University of Sergipe, Aracaju, Brazil;
Search for other papers by Angela Maria da Silva in
Current site
Google Scholar
PubMed
Steven M. Holland
Steven M. Holland
Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
Search for other papers by Steven M. Holland in
Current site
Google Scholar
PubMed
Search for other papers by Steven M. Holland in
Current site
Google Scholar
PubMed
Amelia Ribeiro de Jesus
Amelia Ribeiro de Jesus
Laboratory of Immunology and Molecular Biology, Federal University of Sergipe, Aracaju, Brazil;
Health Sciences Graduate Program, Federal University of Sergipe, Aracaju, Brazil;
Department of Medicine, University Hospital, Federal University of Sergipe, Aracaju, Brazil;
Search for other papers by Amelia Ribeiro de Jesus in
Current site
Google Scholar
PubMed
Health Sciences Graduate Program, Federal University of Sergipe, Aracaju, Brazil;
Department of Medicine, University Hospital, Federal University of Sergipe, Aracaju, Brazil;
Search for other papers by Amelia Ribeiro de Jesus in
Current site
Google Scholar
PubMed
ABSTRACT.
This report documents the first known cases of lepromatous leprosy in patients with chronic mucocutaneous candidiasis (CMC) linked to a gain-of-function mutation in the STAT1 gene. Two related patients, a mother and daughter, who both suffer from CMC and lepromatous leprosy, carry a heterozygous STAT1 mutation (c.821G>A; p.R274Q). Both individuals exhibited similarly high levels of total and phosphorylated STAT1 in CD4+ T cells and decreased interleukin 17A transcripts. This mutation underscores a complex relationship between genetic susceptibility to infections and the necessity to evaluate each case individually.
Author Notes
Financial support: As part of a major cohort study, the present report was supported by
Disclosures: The study is part of a cohort study that was approved by the ethics committee at the Federal University of Sergipe (CAAE 0152.0.107.000-07). Written informed consent was obtained from all family members. Patient consented to publication of partial photographs without identification.
Authors’ contributions: Clinical evaluation and follow-up: G. C. Caldas, L. Menezes-Silva, N. A. dos Santos, A. M. da Silva, and A. R. de Jesus; Perform genetic analysis: S. M. Holland; Data analysis: L. L. de Oliveira Rekowski, P. L. Santos, R. L. L. da Silva, A. R. de Jesus; Scientifical revision and analysis: S. M. Holland and A. R. de Jesus; Conceptualization and supervision of all research: A. R. de Jesus; Write manuscript: C. N. O. Santos, L. S. Magalhães, S. M. Holland, and A. R. de Jesus.
Current contact information: Lais Lima de Oliveira Rekowski, Gustavo Costa Caldas, Lucas Menezes-Silva, Camilla Natália Oliveira Santos, Rodrigo Anselmo Cazzaniga, Nailson Alves dos Santos, Priscila Lima Santos, Ricardo Luís Louzada da Silva, Angela Maria da Silva, and Amelia Ribeiro de Jesus, Universidade Federal de Sergipe, Aracaju, Brazil, E-mails: lais.lima.oliveira@gmail.com, gustaavocaaldas@gmail.com, lucas.mnzsilva@gmail.com, camilla.natallia@hotmail.com, cazzaniga.rodrigo@gmail.com, drnana6@gmail.com, plimabio@gmail.com, qjobio@gmail.com, angela.silva910@gmail.com, and ameliaribeirodejesus@gmail.com. Lucas Sousa Magalhães, Universidade Federal de Sergipe, Aracaju, Brazil, and Universidade Federal de Alagoas, Maceió, Brazil, E-mail: lucas.smagalhaes@hotmail.com. Steven M. Holland, National Institutes of Health, Bethesda, MD, E-mail: sholland@niaid.nih.gov.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Villarino AV, Kanno Y, O’Shea JJ, 2017. Mechanisms and consequences of Jak-STAT signaling in the immune system. Nat Immunol 18: 374–384.
-
2.
Hu X, Li J, Fu M, Zhao X, Wang W, 2021. The JAK/STAT signaling pathway: From bench to clinic. Signal Transduct Target Ther 6: 402.
-
3.
Zhang W, Chen X, Gao G, Xing S, Zhou L, Tang X, Zhao X, An Y, 2021. Clinical relevance of gain- and loss-of-function germline mutations in STAT1: A systematic review. Front Immunol 12: 654406.
-
4.
Bernasconi AR, Yancoski J, Villa M, Oleastro MM, Galicchio M, Rossi JG, 2018. Increased STAT1 amounts correlate with the phospho-STAT1 level in STAT1 gain-of-function defects. J Clin Immunol 38: 745–747.
-
5.
Boehmer DFR, et al., 2020. A novel complete autosomal-recessive STAT1 LOF variant causes immunodeficiency with hemophagocytic lymphohistiocytosis-like hyperinflammation. J Allergy Clin Immunol Pract 8: 3102–3111.
-
6.
Scott O, Lindsay K, Erwood S, Mollica A, Roifman CM, Cohn RD, Ivakine EA, 2021. STAT1 gain-of-function heterozygous cell models reveal diverse interferon-signature gene transcriptional responses. NPJ Genom Med 6: 34.
-
7.
Le Voyer T, et al., 2021. Genetic, immunological, and clinical features of 32 patients with autosomal recessive STAT1 deficiency. J Immunol 207: 133–152.
-
8.
Bezerra-Santos M, et al., 2018. Mycobacterium leprae recombinant antigen induces high expression of multifunction T lymphocytes and is promising as a specific vaccine for leprosy. Front Immunol 9: 2920.
-
9.
Santos CNO, Caldas GC, de Oliveira FA, da Silva AM, da Silva JS, da Silva RLL, de Jesus AR, Magalhães LS, de Almeida RP, 2023. COVID-19 recurrence is related to disease-early profile T cells while detection of anti-S1 IgG is related to multifunctional T cells. Med Microbiol Immunol (Berl) 212: 339–347.
-
10.
Magalhães LS, et al., 2022. Use of N-acetylcysteine as treatment adjuvant regulates immune response in visceral leishmaniasis: Pilot clinical trial and in vitro experiments. Front Cell Infect Microbiol 12: 1045668.
-
11.
Okada S, Asano T, Moriya K, Boisson-Dupuis S, Kobayashi M, Casanova J-L, Puel A, 2020. Human STAT1 gain-of-function heterozygous mutations: Chronic mucocutaneous candidiasis and type I interferonopathy. J Clin Immunol 40: 1065–1081.
-
12.
Toubiana J, et al., 2016. Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype. Blood 127: 3154–3164.
-
13.
Borgström EW, et al., 2022. Three adult cases of STAT1 gain-of-function with chronic mucocutaneous candidiasis treated with JAK inhibitors. J Clin Immunol 43: 136–150.
-
14.
Sampaio EP, et al., 2012. A novel STAT1 mutation associated with disseminated mycobacterial disease. J Clin Immunol 32: 681–689.
-
15.
Kataoka S, et al., 2016. Extrapulmonary tuberculosis mimicking Mendelian susceptibility to mycobacterial disease in a patient with signal transducer and activator of transcription 1 (STAT1) gain-of-function mutation. J Allergy Clin Immunol 137: 619–622.e1.
-
16.
Lyra PT, Falcão ACAM, Cruz RA, Coelho AVC, Souza EDS, Alencar LCA, Oliveira JB, 2022. Gain-of-function STAT1 mutation and visceral leishmaniasis. Einstein (São Paulo) 20: eRC0048.
-
17.
Fujiki R, Hijikata A, Shirai T, Okada S, Kobayashi M, Ohara O, 2017. Molecular mechanism and structural basis of gain-of-function of STAT1 caused by pathogenic R274Q mutation. J Biol Chem 292: 6240–6254.
-
18.
Yamazaki Y, et al., 2014. Two novel gain-of-function mutations of STAT1 responsible for chronic mucocutaneous candidiasis disease: Impaired production of IL-17A and IL-22, and the presence of anti–IL-17F autoantibody. J Immunol 193: 4880–4887.
-
19.
Zimmerman O, et al., 2019. STAT1 gain-of-function mutations cause high total STAT1 levels with normal dephosphorylation. Front Immunol 10: 1433.
-
20.
Parackova Z, Zentsova I, Vrabcova P, Sediva A, Bloomfield M, 2023. Aberrant tolerogenic functions and proinflammatory skew of dendritic cells in STAT1 gain-of-function patients may contribute to autoimmunity and fungal susceptibility. Clin Immunol 246: 109174.
-
21.
Parackova Z, Vrabcova P, Zentsova I, Sediva A, Bloomfield M, 2023. Neutrophils in STAT1 gain-of-function have a pro-inflammatory signature which is not rescued by JAK inhibition. J Clin Immunol 43: 1640–1659.
-
22.
Tamaura M, et al., 2020. Human gain-of-function STAT1 mutation disturbs IL-17 immunity in mice. Int Immunol 32: 259–272.
-
23.
Ling Y, et al., 2015. Inherited IL-17RC deficiency in patients with chronic mucocutaneous candidiasis. J Exp Med 212: 619.
-
24.
Liu L, et al., 2011. Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis. J Exp Med 208: 1635–1648.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 638 | 638 | 509 |
| Full Text Views | 22 | 22 | 13 |
| PDF Downloads | 32 | 32 | 18 |