Novel STAT1 Variants in Japanese Patients with Isolated Mendelian Susceptibility to Mycobacterial Diseases.
Bacille de Calmette et Guérin (BCG)
Inborn error of immunity (IEI)
Mendelian susceptibility to mycobacterial disease (MSMD)
STAT1
Journal
Journal of clinical immunology
ISSN: 1573-2592
Titre abrégé: J Clin Immunol
Pays: Netherlands
ID NLM: 8102137
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
received:
30
03
2022
accepted:
20
10
2022
pubmed:
7
11
2022
medline:
4
2
2023
entrez:
6
11
2022
Statut:
ppublish
Résumé
Heterozygous dominant-negative (DN) STAT1 variants are responsible for autosomal dominant (AD) Mendelian susceptibility to mycobacterial disease (MSMD). In this paper, we describe eight MSMD cases from four kindreds in Japan. An inborn error of immunity-related gene panel sequencing was performed using genomic DNA extracted from whole blood samples. The identified variants were validated using Sanger sequencing. Functional analysis was evaluated with a luciferase reporter assay and co-transfection assay in STAT1-deficient cells. Patient 1.1 was a 20-month-old boy with multifocal osteomyelitis and paravertebral abscesses caused by Mycobacterium bovis bacillus Calmette-Guérin (BCG). Although the paravertebral abscess was refractory to antimycobacterial drugs, the addition of IFN-γ and drainage of the abscess were effective. Intriguingly, his mother (patient 1.2) showed an uneventful clinical course except for treatment-responsive tuberculous spondylitis during adulthood. Patient 2.1 was an 8-month-old boy with lymphadenopathy and lung nodules caused by BCG. He responded well to antimycobacterial drugs. His mother (patient 2.2) was healthy. Patient 3.1 was a 11-year-old girl with suspected skin tuberculosis. Her brother (patient 3.2) had BCG-osis, but their mother (patient 3.3) was healthy. Patient 4 was an 8-month-old girl with left axillary and supraclavicular lymphadenopathy associated with BCG vaccination. Kindreds 1, 2, and 3 were shown to have novel heterozygous variants (V642F, R588C, and R649G) in STAT1, respectively. Kindred 4 had previously reported heterozygous variants (Q463H). A luciferase reporter assay in STAT1-deficient cells followed by IFN-γ stimulation confirmed that these variants are loss-of-function. In addition, with co-transfection assay, we confirmed all of these variants had DN effect on WT STAT1. Four kindred MSMD subjects with 3 novel variants and 1 known variant in STAT1 were identified in this study. AD STAT1 deficiency might be prevalent in Japanese patients with BCG-associated MSMD.
Identifiants
pubmed: 36336768
doi: 10.1007/s10875-022-01396-1
pii: 10.1007/s10875-022-01396-1
doi:
Substances chimiques
BCG Vaccine
0
Anti-Bacterial Agents
0
STAT1 protein, human
0
STAT1 Transcription Factor
0
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
466-478Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Rosain J, Kong XF, Martinez-Barricarte R, Oleaga-Quintas C, Ramirez-Alejo N, Markle J, et al. Mendelian susceptibility to mycobacterial disease: 2014–2018 update. Immunol Cell Biol. 2019;97:360–7.
doi: 10.1111/imcb.12210
Hosaka S, Kido T, Imagawa K, Fukushima H, Morio T, Nonoyama S, et al. Vaccination for patients with inborn errors of immunity: a nationwide survey in Japan. J Clin Immunol. 2022;42:183–94.
doi: 10.1007/s10875-021-01160-x
Bustamante J, Boisson-Dupuis S, Abel L, Casanova JL. Mendelian susceptibility to mycobacterial disease: genetic, immunological, and clinical features of inborn errors of IFN-γ immunity. Semin Immunol. 2014;26:454–70.
doi: 10.1016/j.smim.2014.09.008
Bustamante J. Mendelian susceptibility to mycobacterial disease: recent discoveries. Hum Genet. 2020;139:993–1000.
doi: 10.1007/s00439-020-02120-y
Martin-Fernandez M, Buta S, Le Voyer T, Li Z, Dynesen LT, Vuillier F, et al. A partial form of inherited human USP18 deficiency underlies infection and inflammation. J Exp Med. 2022;219: e20211273.
doi: 10.1084/jem.20211273
Le Voyer T, Sakata S, Tsumura M, Khan T, Esteve-Sole A, Al-Saud BK, et al. Genetic, immunological, and clinical features of 32 patients with autosomal recessive STAT1 deficiency. J Immunol. 2021;207:133–52.
doi: 10.4049/jimmunol.2001451
Mizoguchi Y, Okada S. Inborn errors of STAT1 immunity. Curr Opin Immunol. 2021;72:59–64.
doi: 10.1016/j.coi.2021.02.009
Bhattad S, Unni J, Varkey S. MSMD in a 3-generation multiplex kindred due to autosomal dominant STAT1 deficiency. J Clin Immunol. 2021;41:259–61.
doi: 10.1007/s10875-020-00890-8
Liu Z, Zhou M, Yuan C, Ni Z, Liu W, Tan Y, et al. Two novel STAT1 mutations cause Mendelian susceptibility to mycobacterial disease. Biochem Biophys Res Commun. 2022;591:124–9.
doi: 10.1016/j.bbrc.2021.11.036
Chen X, Chen J, Chen R, Mou H, Sun G, Yang L, et al. Genetic and functional identifying of novel STAT1 loss-of-function mutations in patients with diverse clinical phenotypes. J Clin Immunol. 2022. https://doi.org/10.1007/s10875-022-01339-w .
Tangye SG, AL-Herz W, Bousfiha A, Chatila T, Cunningham-Rundles C, Etzioni A, et al. Human inborn errors of immunity: 2019 update on the classification from the international union of immunological societies expert committee. J Clin Immunol. 2020;40:24–64.
doi: 10.1007/s10875-019-00737-x
Kagawa R, Fujiki R, Tsumura M, Sakata S, Nishimura S, Itan Y, et al. Alanine-scanning mutagenesis of human signal transducer and activator of transcription 1 to estimate loss- or gain-of-function variants. J Allergy Clin Immunol. 2017;140:232–41.
doi: 10.1016/j.jaci.2016.09.035
Shionoya A, Yoto Y, Hida T, Ishikawa A, Hasegawa T, Tsugawa T, et al. Bacillus Calmette-Guérin-induced lupus vulgaris in a patient with Mendelian susceptibility to mycobacterial disease caused by a novel STAT1 variation. Br J Dermatol. In press
Chapgier A, Boisson-Dupuis S, Jouanguy E, Vogt G, Feinberg J, Prochnicka-Chalufour A, et al. Novel STAT1 alleles in otherwise healthy patients with mycobacterial disease. PLoS Genet. 2006;2: e131.
doi: 10.1371/journal.pgen.0020131
Liu L, Okada S, Kong XF, Kreins AY, Cypowyj S, Abhyankar A, et al. Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis. J Exp Med. 2011;208:1635–48.
doi: 10.1084/jem.20110958
Hirata O, Okada S, Tsumura M, Kagawa R, Miki M, Kawaguchi H, et al. Heterozygosity for the Y701C STAT1 mutation in a multiplex kindred with multifocal osteomyelitis. Haematologica. 2013;98:1641–9.
doi: 10.3324/haematol.2013.083741
Chen X, Vinkemeier U, Zhao Y, Jeruzalmi D, Darnell JE Jr, Kuriyan J. Crystal structure of a tyrosine phosphorylated STAT-1 dimer bound to DNA. Cell. 1998;93:827–39.
doi: 10.1016/S0092-8674(00)81443-9
Dupuis S, Jouanguy E, Al-Hajjar S, Fieschi C, Al-Mohsen IZ, Al-Jumaah S, et al. Impaired response to interferon-alpha/beta and lethal viral disease in human STAT1 deficiency. Nat Genet. 2003;33:388–91.
doi: 10.1038/ng1097
Dupuis S, Dargemont C, Fieschi C, Thomassin N, Rosenzweig S, Harris J, et al. Impairment of mycobacterial but not viral immunity by a germline human STAT1 mutation. Science. 2001;293:300–3.
doi: 10.1126/science.1061154
Sampaio EP, Bax HI, Hsu AP, Kristosturyan E, Pechacek J, Chandrasekaran P, et al. A novel STAT1 mutation associated with disseminated mycobacterial disease. J Clin Immunol. 2012;32:681–9.
doi: 10.1007/s10875-012-9659-2
Tsumura M, Okada S, Sakai H, Yasunaga S, Ohtsubo M, Murata T, et al. Dominant-negative STAT1 SH2 domain mutations in unrelated patients with Mendelian susceptibility to mycobacterial disease. Hum Mutat. 2012;33:1377–87.
doi: 10.1002/humu.22113
Ueki M, Yamada M, Ito K, Tozawa Y, Morino S, Horikoshi Y, et al. A heterozygous dominant-negative mutation in the coiled-coil domain of STAT1 is the cause of autosomal-dominant Mendelian susceptibility to mycobacterial diseases. Clin Immunol. 2017;174:24–31.
doi: 10.1016/j.clim.2016.11.004
Ying W, Liu D, Dong X, Wang W, Hui X, Hou J, et al. Current status of the management of Mendelian susceptibility to mycobacterial disease in Mainland China. J Clin Immunol. 2019;39:600–10.
doi: 10.1007/s10875-019-00672-x
Chapgier A, Wynn RF, Jouanguy E, Filipe-Santos O, Zhang S, Feinberg J, et al. Human complete Stat-1 deficiency is associated with defective type I and II IFN responses in vitro but immunity to some low virulence viruses in vivo. J Immunol. 2006;176:5078–83.
doi: 10.4049/jimmunol.176.8.5078
Chapgier A, Kong XF, Boisson-Dupuis S, Jouanguy E, Averbuch D, Feinberg J. A partial form of recessive STAT1 deficiency in humans. J Clin Invest. 2009;119:1502–14.
doi: 10.1172/JCI37083
Sakai T, Matsuoka M, Aoki M, Nosaka K, Mitsuya H. Missense mutation of the interleukin-12 receptor beta1 chain-encoding gene is associated with impaired immunity against Mycobacterium avium complex infection. Blood. 2001;97:2688–94.
doi: 10.1182/blood.V97.9.2688
Sasaki Y, Nomura A, Kusuhara K, Takada H, Ahmed S, Obinata K, et al. Genetic basis of patients with bacille Calmette-Guérin osteomyelitis in Japan: identification of dominant partial interferon-gamma receptor 1 deficiency as a predominant type. J Infect Dis. 2002;185:706–9.
doi: 10.1086/339011
Okada S, Ishikawa N, Shirao K, Kawaguchi H, Tsumura M, Ohno Y, et al. The novel IFNGR1 mutation 774del4 produces a truncated form of interferon-gamma receptor 1 and has a dominant-negative effect on interferon-gamma signal transduction. J Med Genet. 2007;44:485–91.
doi: 10.1136/jmg.2007.049635
Hoshina T, Takada H, Sasaki-Mihara Y, Kusuhara K, Ohshima K, Okada S, et al. Clinical and host genetic characteristics of Mendelian susceptibility to mycobacterial diseases in Japan. J Clin Immunol. 2011;31:309–14.
doi: 10.1007/s10875-010-9498-y
Obinata K, Lee T, Niizuma T, Kinoshita K, Shimizu T, Hoshina T, et al. Two cases of partial dominant interferon-γ receptor 1 deficiency that presented with different clinical courses of bacille Calmette-Guérin multiple osteomyelitis. J Infect Chemother. 2013;19:757–60.
doi: 10.1007/s10156-012-0493-5
Takeda K, Kawai T, Nakazawa Y, Komuro H, Shoji K, Morita K, et al. Augmentation of antitubercular therapy with IFNγ in a patient with dominant partial IFNγ receptor 1 deficiency. Clin Immunol. 2014;151:25–8.
doi: 10.1016/j.clim.2014.01.004
Tomomasa D, Tanita K, Higashi S, Tasaka Y, Shimamura T, Sakurai U, et al. Early diagnosis of partial interferon-γ receptor 1 deficiency prevents the development of Bacille de Calmette et Guérin osteomyelitis. Clin Immunol. 2022;235:108933. https://doi.org/10.1016/j.clim.2022.108933 .
doi: 10.1016/j.clim.2022.108933
Al-Muhsen S, Casanova JL. The genetic heterogeneity of mendelian susceptibility to mycobacterial diseases. J Allergy Clin Immunol. 2008;122:1043–51.
doi: 10.1016/j.jaci.2008.10.037
Esteve-Solé A, Sologuren I, Martínez-Saavedra MT, Deyà-Martínez À, Oleaga-Quintas C, Martinez-Barricarte R, et al. Laboratory evaluation of the IFN-γ circuit for the molecular diagnosis of Mendelian susceptibility to mycobacterial disease. Crit Rev Clin Lab Sci. 2018;55:184–204.
doi: 10.1080/10408363.2018.1444580