Advertisement

Short Stature, Prolonged Fever and Lymphoproliferation

  • Maria Kanariou
  • Sofia Tantou
  • Kosmas Kotsonis
Chapter

Abstract

Studies on patients with STAT3 mutations, will expand the understanding of the pathophysiology of STAT3 function and its importance in regulating the immune system

Membrane-bound interleukin 6 receptor tocilizumab, and Janus kinase inhibitors have been successfully implemented to control lymphoproliferation in patients with STAT3 gain-of-function mutation

Keywords

STAT3 Tocilizumab Janus kinase Lymphoproliferation 

References

  1. 1.
    van der Burg M, Gennery AR. Educational paper. The expanding clinical and immunological spectrum of severe combined immunodeficiency. Eur J Pediatr. 2011;170(5):561–71.CrossRefGoogle Scholar
  2. 2.
    Wong T, Yeung J, Hildebrand KJ, Junker AK, Turvey SE. Human primary immunodeficiencies causing defects in innate immunity. Curr Opin Allergy Clin Immunol. 2013;13(6):607–13.CrossRefGoogle Scholar
  3. 3.
    Doffinger R, Patel S, Kumararatne DS. Human immunodeficiencies that predispose to intracellular bacterial infections. Curr Opin Rheumatol. 2005;17(4):440–6.CrossRefGoogle Scholar
  4. 4.
    Rezaei N, Hedayat M, Aghamohammadi A, Nichols KE. Primary immunodeficiency diseases associated with increased susceptibility to viral infections and malignancies. J Allergy Clin Immunol. 2011;127(6):1329–41.e2; quiz 42–3.CrossRefGoogle Scholar
  5. 5.
    Picard C, Al-Herz W, Bousfiha A, Casanova JL, Chatila T, Conley ME, Cunningham-Rundles C, Etzioni A, Holland SM, Klein C, Nonoyama S, Ochs HD, Oksenhendler E, Puck JM, Sullivan KE, Tang ML, Franco JL, Gaspar HB. Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015. J Clin Immunol. 2015;35(8):696–726.CrossRefGoogle Scholar
  6. 6.
    Casanova JL, Holland SM, Notarangelo LD. Inborn errors of human JAKs and STATs. Immunity. 2012;36(4):515–28.CrossRefGoogle Scholar
  7. 7.
    O’Shea JJ, Holland SM, Staudt LM. JAKs and STATs in immunity, immunodeficiency, and cancer. N Engl J Med. 2013;368(2):161–70.CrossRefGoogle Scholar
  8. 8.
    Villarino AV, Kanno Y, Ferdinand JR, O’Shea JJ. Mechanisms of Jak/STAT signaling in immunity and disease. J Immunol. 2015;194(1):21–7.CrossRefGoogle Scholar
  9. 9.
    Lorenzini T, Dotta L, Giacomelli M, Vairo D, Badolato R. STAT mutations as program switchers: turning primary immunodeficiencies into autoimmune diseases. J Leukoc Biol. 2017;101(1):29–38.CrossRefGoogle Scholar
  10. 10.
    Haapaniemi EM, Kaustio M, Rajala HL, van Adrichem AJ, Kainulainen L, Glumoff V, Doffinger R, Kuusanmaki H, Heiskanen-Kosma T, Trotta L, Chiang S, Kulmala P, Eldfors S, Katainen R, Siitonen S, Karjalainen-Lindsberg ML, Kovanen PE, Otonkoski T, Porkka K, Heiskanen K, Hanninen A, Bryceson YT, Uusitalo-Seppala R, Saarela J, Seppanen M, Mustjoki S, Kere J. Autoimmunity, hypogammaglobulinemia, lymphoproliferation, and mycobacterial disease in patients with activating mutations in STAT3. Blood. 2015;125(4):639–48.CrossRefGoogle Scholar
  11. 11.
    Milner JD, Vogel TP, Forbes L, Ma CA, Stray-Pedersen A, Niemela JE, Lyons JJ, Engelhardt KR, Zhang Y, Topcagic N, Roberson ED, Matthews H, Verbsky JW, Dasu T, Vargas-Hernandez A, Varghese N, McClain KL, Karam LB, Nahmod K, Makedonas G, Mace EM, Sorte HS, Perminow G, Rao VK, O’Connell MP, Price S, Su HC, Butrick M, McElwee J, Hughes JD, Willet J, Swan D, Xu Y, Santibanez-Koref M, Slowik V, Dinwiddie DL, Ciaccio CE, Saunders CJ, Septer S, Kingsmore SF, White AJ, Cant AJ, Hambleton S, Cooper MA. Early-onset lymphoproliferation and autoimmunity caused by germline STAT3 gain-of-function mutations. Blood. 2015;125(4):591–9.CrossRefGoogle Scholar
  12. 12.
    Khoury T, Molho-Pessach V, Ramot Y, Ayman AR, Elpeleg O, Berkman N, Zlotogorski A, Ilan Y. Tocilizumab promotes regulatory T-cell alleviation in STAT3 gain-of-function-associated multi-organ autoimmune syndrome. Clin Ther. 2017;39(2):444–9.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Maria Kanariou
    • 1
  • Sofia Tantou
    • 1
  • Kosmas Kotsonis
    • 2
  1. 1.Department of Immunology-HistocompatibilitySpecialized Center & Referral Center for Primary Immunodeficiencies, Pediatric Immunology, “Aghia Sophia” Children’s HospitalAthensGreece
  2. 2.1st Paediatric Clinic, “Aghia Sophia” Children’s HospitalAthensGreece

Personalised recommendations