HyperImmunoglobulin E Syndrome: Clinical and Immunologic Evaluation within One Family 41

Abstract

Hyper IgE syndrome (HIE) is characterized by recurrent staphylococcal deep-seated infections, mucocutaneous candidiasis, chronic eczematous dermatitis, bone fractures, and coarse facies. A father and two daughters (now 1 and 5 yrs old) with classical manifestations of HIE provided a unique opportunity for early and sequential evaluation of clinical and immunologic parameters. Extremely high serum IgE may be caused by abnormalities in T lymphocyte function and cytokine production. Measurements of T cell populations and cytokines that control IgE production, IL-4 and IFN-γ, have found variable results in HIE. In this family, IgE levels were 0 - 100 IU/ml in the first year of life, rising to >36000 at 4 yrs in one child. T cell responses to mitogens and antigens were already decreased. In the first year, the absolute CD 4 counts were increased (mean 5670) with normal percentages due to elevated total lymphocyte counts. CD8 counts near the lower limit of normal (mean 600) resulted in elevated CD4:CD8 ratios (range 5 to 11). Naive CD4CD45RA and committed CD4CD45RO showed a normal pattern: CD45RA decreased with age while CD45RO increased. Neutrophil dysfunction, especially in chemotaxis, also is reported in HIE. Assessment of neutrophil receptors showed a significantly decreased expression of the CD11b/CD18 heterodimer at 38%/35% for the younger child and 33%/45% for the older girl. In contrast, neutrophils from their father expressed CD11b/CD18 at normal levels. FcRIII(CD16) expression on neutrophils showed a strikingly different pattern: both children had a dual population of cells. 25-45% of neutrophils had decreased expression at 50% control, but 75-55% of cells had greatly upregulated FcRIII from 3.4 to 67 times normal. The father had a single population of FcRIII at 180% of control. Changes in IgE levels, T lymphocytes, and the expression of neutrophil receptors within this family suggest an age-related pattern. These findings may help in understanding the functional abnormalities, and potentially to identify the genetic defect in this rare primary immunodeficiency syndrome.