Human Immunodeficiencies Resulting From Defective NF-κB Activation

Human immune deficiencies due to defective NF-κB transcription factor activation present classically with anhidrotic ectodermal dysplasia with immune deficiency. The severity of the immune deficiency is highly variable, ranging from significant defects in T and B lymphocyte development and function with impaired inflammatory responses due to innate immune defects, to milder immune deficiencies with subtler T and B lymphocyte defects and little or no impairment in innate immune function. Furthermore, some of these patients do not develop anhidrotic ectodermal dysplasia, which can delay diagnosis. Analysis of the immune functions and developmental defects associated with the numerous mutations within the NF-κB pathway has provided valuable information about the complex regulation of NF-κB activation and the cellular processes that NF-κB regulates. Many of these patients are susceptible to a broad range of invasive bacterial infections, DNA viral infections, and opportunistic infections. Some patients are adequately managed with prophylactic antibiotics and replacement immunoglobulins, while stem cell transplantation should be considered for the more severe phenotypes.