Primary NK immunodeficiencies

Keeping on the topic of natural killer cells, Jordan Orange, MD, PhD contributes a review on immunodeficiencies associated with NK cell dysfunction [J Allergy Clin Immunol 2013; 132(3):515-525].  The author provides a concise review of NK cell biology, covering their intrinsic activities of cytotoxicity, tumor surveillance, and co-stimulation and signaling.  Orange points out that NK cell deficiency [NKD] is a subset of primary immunodeficiency diseases [PID] that is difficult to diagnose and treat because of the limited clinical information and testing available. 

Like other PID, the author notes that NKD patients are characterized by a susceptibility to chronic and/or severe viral infections, especially herpes viruses.  Accurate diagnosis hinges on determining that the seminal deficiency is associated with NK cells, and that NKD is not secondary to other causes. The author provides an algorithm for identifying primary NKD. 

Orange discusses the current classification of NKD into two types:  classical NKD and functional NKD.  Classical NKD [CNKD] is characterized by severe depletion or absence of NK cells in peripheral blood, while functional NKD [FNKD] is typified by the presence of peripheral NK cells with impaired or abrogated activity.  He points out that there is some overlap in these phenotypes in the reported cases.  Orange further discusses the subtypes of CKND and their associated genetic abnormalities.  In his discussion of FNKD, the author reports on the first identified subtype, FNKD1, which involves a defect in the IgG receptor. 

Orange continues describing the clinical cases that have been reported and the availability and applicability of diagnostics for NKD.  The author also reviews briefly other PID that effect NK cell immunity, but that affect other components of the immune system in the majority.  Addressing the clinical treatment of NKD, he notes that intervention is focused on the herpetic infection susceptibility and employs approved antivirals such as gancyclovir.  Additionally, the author reports that severe presentations of NKD have been treated successfully with stem cell transplantation.