PURPOSE OF THE STUDY.
The goal of this study was to characterize a form of severe combined immunodeficiency (SCID) that has previously been described.
The study included 4 patients of Northern Cree ancestry from Canada, who presented with normal numbers of T cells and B cells but very low levels of immunoglobulins, as well as a severe defect in activation of immune cells, which affected both the innate and adaptive immune-receptor pathways. These patients presented with oral candidiasis, Escherichia coli septicemia, parainfluenza virus type 1 pneumonia, Listeria monocytogenes septicemia, parainfluenza virus type 3 pneumonia, and Serratia marcescens bacteremia.
Immunologic phenotyping, genetic and protein analyses, and functional investigations were performed.
The patients all had hypogammaglobulinemia or agammaglobulinemia, and peripheral blood B and T cells were almost exclusively of naive phenotype. Regulatory T cells and γδ T cells were absent. All 4 patients carried a homozygous duplication that led to loss of expression of IKK2, which is a component of the IKK-nuclear factor κB pathway. Immune cells from these patients had impaired responses to stimulation through T-cell receptors, B-cell receptors, toll-like receptors, inflammatory cytokine receptors, and mitogens.
This form of SCID is characterized by normal lymphocyte development despite a loss of IKK2 function. This deficiency results in an impaired response to activation stimuli in a variety of immune cells, which leads to severe impairment of adaptive and innate immunity.
SCID is rare, but most pediatricians will encounter this diagnosis sooner or later. It is important to be vigilant with children who have unusual, frequent, and persistent infections. In this case, the presence of normal numbers of T cells and B cells did not rule out the diagnosis of SCID.
- Copyright © 2014 by the American Academy of Pediatrics