Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

NK cell deficiency syndromes: Treatment

Jordan S Orange, MD, PhD
Section Editor
E Richard Stiehm, MD
Deputy Editor
Anna M Feldweg, MD


Natural killer (NK) cell deficiency syndromes are rare disorders in which NK cells are absent, deficient, or dysfunctional, in the absence of any other identifiable immunodeficiency, genetic disorder, or medication known to affect NK cells. These disorders are categorized as classical NK cell deficiency (CNKD) and functional NK cell deficiency (FNKD).

In CNKD, NK cell developmental status or survival is abnormal, often leading to decreased NK cell numbers in the peripheral blood.

In FNKD, NK cells are appropriately developed and present but are functionally impaired.

The management of patients with these disorders is discussed here. The biology of NK cells, the clinical manifestations of NK cell disorders, and the evaluation of patients suspected of having NK cell defects are presented separately. (See "NK cell deficiency syndromes: Clinical manifestations and diagnosis".)


Therapy for patients with NK cell deficiency syndromes is largely empiric, due to the small numbers of cases described in the literature. Active infections must be identified and treated aggressively, as with any immunodeficiency. (See "Primary immunodeficiency: Overview of management".)

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Aug 31, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Biron CA, Nguyen KB, Pien GC, et al. Natural killer cells in antiviral defense: function and regulation by innate cytokines. Annu Rev Immunol 1999; 17:189.
  2. Lotzová E, Savary CA, Schachner JR, et al. Generation of cytotoxic NK cells in peripheral blood and bone marrow of patients with acute myelogenous leukemia after continuous infusion with recombinant interleukin-2. Am J Hematol 1991; 37:88.
  3. Azuma H, Oshima M, Ito K, et al. Impaired interleukin-2 production in T-cells from a patient with Wiskott-Aldrich syndrome: basis of clinical effect of interleukin-2 replacement therapy. Eur J Pediatr 2000; 159:633.
  4. Orange JS, Brodeur SR, Jain A, et al. Deficient natural killer cell cytotoxicity in patients with IKK-gamma/NEMO mutations. J Clin Invest 2002; 109:1501.
  5. Orange JS, Roy-Ghanta S, Mace EM, et al. IL-2 induces a WAVE2-dependent pathway for actin reorganization that enables WASp-independent human NK cell function. J Clin Invest 2011; 121:1535.
  6. Meropol NJ, Porter M, Blumenson LE, et al. Daily subcutaneous injection of low-dose interleukin 2 expands natural killer cells in vivo without significant toxicity. Clin Cancer Res 1996; 2:669.
  7. Toren A, Nagler A, Rozenfeld-Granot G, et al. Amplification of immunological functions by subcutaneous injection of intermediate-high dose interleukin-2 for 2 years after autologous stem cell transplantation in children with stage IV neuroblastoma. Transplantation 2000; 70:1100.
  8. Mossman KL, Ashkar AA. Herpesviruses and the innate immune response. Viral Immunol 2005; 18:267.
  9. Cac NN, Ballas ZK. Recalcitrant warts, associated with natural killer cell dysfunction, treated with systemic IFN-alpha. J Allergy Clin Immunol 2006; 118:526.
  10. Mace EM, Hsu AP, Monaco-Shawver L, et al. Mutations in GATA2 cause human NK cell deficiency with specific loss of the CD56(bright) subset. Blood 2013; 121:2669.
  11. Notarangelo LD, Mazzolari E. Natural killer cell deficiencies and severe varicella infection. J Pediatr 2006; 148:563.
  12. Tzannou I, Papadopoulou A, Naik S, et al. Off-the-Shelf Virus-Specific T Cells to Treat BK Virus, Human Herpesvirus 6, Cytomegalovirus, Epstein-Barr Virus, and Adenovirus Infections After Allogeneic Hematopoietic Stem-Cell Transplantation. J Clin Oncol 2017; 35:3547.
  13. Naik S, Nicholas SK, Martinez CA, et al. Adoptive immunotherapy for primary immunodeficiency disorders with virus-specific T lymphocytes. J Allergy Clin Immunol 2016; 137:1498.