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Interferon-γ Receptor 1 Deficiency Corrected by Umbilical Cord Blood Transplantation

  • Thomas F. Michniacki
  • Kelly J. Walkovich
  • David G. Frame
  • Mark T. Vander LugtEmail author
Letter to Editor
  • 26 Downloads

To the Editor:

Interferon-gamma receptor (IFNGR)–related disorders are rare variants of Mendelian susceptibility to mycobacterial diseases (MSMD). Given interferon (IFN)–gamma’s crucial role in innate immunity against mycobacterium and intracellular microorganisms, affected individuals are characteristically prone to serious infections with not only weakly virulent mycobacteria species but also Salmonella, Listeria, Histoplasma, and various viruses. Death often occurs in childhood in those with complete receptor deficiencies unless definitive treatment is provided [1, 2, 3]. Although treatment with hematopoietic stem cell transplantation (HSCT) has been described and is curative, it is complicated by high rates of delayed or failed engraftment thought to be due to elevated concentrations of IFN-gamma [4, 5, 6, 7]. Umbilical cord blood transplantation and reduced-intensity conditioning regimens additionally increase the risk of graft failure [8, 9]. Here, we describe a pediatric...

Abbreviations

AUC

Area under the curve

CD

Cluster of differentiation

HLH

Hemophagocytic lymphohistiocytosis

HSCT

Hematopoietic stem cell transplantation

IFN

Interferon

IFNGR

Interferon-gamma receptor

IgG

Immunoglobulin G

IL

Interleukin

IL12R

Interleukin-12 receptor

MSMD

Mendelian susceptibility to mycobacterial diseases

STAT1

Signal transducer and activator of transcription 1

Notes

Acknowledgments

The authors would like to thank the family of our patient for allowing the sharing of his clinical case. We additionally appreciate the assistance of the Clinical Immunology Research Laboratory at the Medical College of Wisconsin, specifically Dr. Jeffrey Woodliff, Dr. John Routes, and Dr. James Verbsky, in performing the diagnostic functional studies that were crucial in characterizing the patient’s defect.

Author Contributions

Dr. Michniacki drafted the manuscript. Drs. Vander Lugt, Frame, and Walkovich assisted in reviewing and editing the manuscript.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

References

  1. 1.
    Dorman SE, Picard C, Lammas D, Heyne K, van Dissel JT, Baretto R, et al. Clinical features of dominant and recessive interferon gamma receptor 1 deficiencies. Lancet. 2004;364:2113–21.CrossRefGoogle Scholar
  2. 2.
    Ramirez-Alejo N, Santos-Argumedo L. Innate defects of the IL-12/IFN-γ axis in susceptibility to infections by mycobacteria and salmonella. J Interf Cytokine Res. 2014;34:307–17.CrossRefGoogle Scholar
  3. 3.
    Cottle LE. Mendelian susceptibility to mycobacterial disease. Clin Genet. 2011;79:17–22.CrossRefGoogle Scholar
  4. 4.
    Roesler J, Horwitz ME, Picard C, Bordigoni P, Davies G, Koscielniak E, et al. Hematopoietic stem cell transplantation for complete IFN-gamma receptor 1 deficiency: a multi-institutional survey. J Pediatr. 2004;145:806–12.CrossRefGoogle Scholar
  5. 5.
    Moilanen P, Korppi M, Hovi L, Chapgier A, Feinberg J, Kong XF, et al. Successful hematopoietic stem cell transplantation from an unrelated donor in a child with interferon gamma receptor deficiency. Pediatr Infect Dis J. 2009;28:658–60.CrossRefGoogle Scholar
  6. 6.
    Rottman M, Soudais C, Vogt G, Renia L, Emile JF, Decaluwe H, et al. IFN-gamma mediates the rejection of haematopoietic stem cells in IFN-gammaR1-deficient hosts. PLoS Med. 2008;5:e26.CrossRefGoogle Scholar
  7. 7.
    de Vor IC, van der Meulen PM, Bekker V, Verhard EM, Breuning MH, Harnisch E, et al. Deletion of the entire interferon-γ receptor 1 gene causing complete deficiency in three related patients. J Clin Immunol. 2016;36:195–203.CrossRefGoogle Scholar
  8. 8.
    Satwani P, Jin Z, Duffy D, Morris E, Bhatia M, Garvin JH, et al. Transplantation-related mortality, graft failure, and survival after reduced-toxicity conditioning and allogeneic hematopoietic stem cell transplantation in 100 consecutive pediatric recipients. Biol Blood Marrow Transplant. 2013;19:552–61.CrossRefGoogle Scholar
  9. 9.
    Wagner JE, Kernan NA, Steinbuch M, et al. Allogeneic sibling umbilical-cord-blood transplantation in children with malignant and non-malignant disease. Lancet. 1995;346:214–9.CrossRefGoogle Scholar
  10. 10.
    Bergsten E, Horne A, Aricó M, Astigarraga I, Egeler RM, Filipovich AH, et al. Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study. Blood. 2017;130:2728–38.CrossRefGoogle Scholar
  11. 11.
    Marsh RA, Haddad E. How i treat primary haemophagocytic lymphohistiocytosis. Br J Haematol. 2018;182:185–99.CrossRefGoogle Scholar
  12. 12.
    Güngör T, Teira P, Slatter M, Stussi G, Stepensky P, Moshous D, et al. Reduced-intensity conditioning and HLA-matched haemopoietic stem-cell transplantation in patients with chronic granulomatous disease: a prospective multicentre study. Lancet. 2014;383:436–48.CrossRefGoogle Scholar
  13. 13.
    de Bruin AM, Demirel Ö, Hooibrink B, Brandts CH, Nolte MA. Interferon-γ impairs proliferation of hematopoietic stem cells in mice. Blood. 2013;121:3578–85.CrossRefGoogle Scholar
  14. 14.
    Maciejewski J, Selleri C, Anderson S, Young NS. Fas antigen expression on CD34+ human marrow cells is induced by interferon gamma and tumor necrosis factor alpha and potentiates cytokine-mediated hematopoietic suppression in vitro. Blood. 1995;85:3183–90.Google Scholar
  15. 15.
    Locatelli F, Jordan MB, Allen CE, et al. Safety and efficacy of emapalumab in pediatric patients with primary hemophagocytic lymphohistiocytosis. Blood. 2018;132:LBA–6-LBA-6.Google Scholar
  16. 16.
    Newport MJ, Huxley CM, Huston S, Hawrylowicz CM, Oostra BA, Williamson R, et al. A mutation in the interferon-gamma-receptor gene and susceptibility to mycobacterial infection. N Engl J Med. 1996;335:1941–9.CrossRefGoogle Scholar
  17. 17.
    Holland SM, Dorman SE, Kwon A, Pitha-Rowe IF, Frucht DM, Gerstberger SM, et al. Abnormal regulation of interferon-gamma, interleukin-12, and tumor necrosis factor-alpha in human interferon-gamma receptor 1 deficiency. J Infect Dis. 1998;178:1095–104.CrossRefGoogle Scholar
  18. 18.
    Jouanguy E, Lamhamedi-Cherradi S, Lammas D, Dorman SE, Fondanèche MC, Dupuis S, et al. A human IFNGR1 small deletion hotspot associated with dominant susceptibility to mycobacterial infection. Nat Genet. 1999;21:370–8.CrossRefGoogle Scholar
  19. 19.
    van de Vosse E, van Dissel JT. IFN-γR1 defects: mutation update and description of the IFNGR1 variation database. Hum Mutat. 2017;38:1286–96.CrossRefGoogle Scholar
  20. 20.
    Noordzij JG, Hartwig NG, Verreck FAW, de Bruin-Versteeg S, de Boer T, Dissel JTV, et al. Two patients with complete defects in interferon gamma receptor-dependent signaling. J Clin Immunol. 2007;27:490–6.CrossRefGoogle Scholar
  21. 21.
    Roesler J, Kofink B, Wendisch J, Heyden S, Paul D, Friedrich W, et al. Listeria monocytogenes and recurrent mycobacterial infections in a child with complete interferon-gamma-receptor (IFNgammaR1) deficiency: mutational analysis and evaluation of therapeutic options. Exp Hematol. 1999;27:1368–74.CrossRefGoogle Scholar
  22. 22.
    HSCT experience in patients with interferon gamma receptor deficiencies. EBMT, https://www.ebmt.org/research/studies/hsct-experience-patients-interferon-gamma-receptor-deficiencies (accessed 18 January 2019).

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pediatrics and Communicable Diseases, Division of Pediatric Hematology/OncologyUniversity of MichiganAnn ArborUSA
  2. 2.Department of PharmacyUniversity of MichiganAnn ArborUSA

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