NK cell deficiency syndromes: Treatment
- Jordan S Orange, MD, PhD
Jordan S Orange, MD, PhD
- Section Editor — Immunology and Immunodeficiency
- Professor of Pediatrics
- Chief of Immunology, Allergy, and Rheumatology
- Baylor College of Medicine
- Texas Children's Hospital
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).
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 natural killer (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 immune disorder. (See "Medical management of immunodeficiency".)
The use of specific therapies is based either on theoretical utility or anecdotal reports of benefit (table 1).
Natural killer (NK) cell disorders are characterized clinically by susceptibility to severe and/or recurrent infection with herpes viruses, including varicella zoster virus (VZV), Herpes simplex virus (HSV) I and II, Epstein Barr virus (EBV), and cytomegalovirus (CMV). There is also a marked susceptibility in some patients to Human Papilloma Viruses.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Mossman KL, Ashkar AA. Herpesviruses and the innate immune response. Viral Immunol 2005; 18:267.
- Cac NN, Ballas ZK. Recalcitrant warts, associated with natural killer cell dysfunction, treated with systemic IFN-alpha. J Allergy Clin Immunol 2006; 118:526.
- 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.
- Notarangelo LD, Mazzolari E. Natural killer cell deficiencies and severe varicella infection. J Pediatr 2006; 148:563.