The relationship between hypogammaglobulinemia, monoclonal gammopathy of undetermined significance and humoral immunodeficiency: a case series.

Hypogammaglobulinemia of the non-monoclonal immunoglobulin heavy chain classes has been reported in monoclonal gammopathy of undetermined significance (MGUS) patients. Whether low polyclonal immunoglobulin levels are associated with impaired specific antibody production and whether they represent a risk factor for the development of recurrent bacterial infections have not been established in this population. We determined the frequency of MGUS in patients referred to a tertiary care clinical immunology ambulatory care practice for evaluation of hypogammaglobulinemia, who were assessed for deficits in specific antibody production and the presence of recurrent infections. Of the 133 patients evaluated for hypogammaglobulinemia, 68 were screened for monoclonal gammopathy and 5 were found to have MGUS. Three had MGUS associated hypogammaglobulinemia in the absence of a defining primary immunodeficiency, one possibly had common variable immunodeficiency, and one had an uncertain diagnosis. Thus, MGUS may be uncovered in patients presenting with hypogammaglobulinemia even in those who lack an elevated serum level of IgG, IgM, or IgA

Secondary immunologic consequences in chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome).

Clinical evidence suggests that patients with Chromosome 22q11.2 deletion (Ch22q11.2D) have an increased prevalence of atopic and autoimmune disease and this has been without explanation. We hypothesized that the increase in atopy was due to homeostatic proliferation of T cells leading to a Th2 skew. We performed intracellular cytokine staining to define Th1/Th2 phenotypes in toddlers (early homeostatic proliferation) and adults (post homeostatic proliferation) with this syndrome. To attempt to understand the predisposition to autoimmunity we performed immunophenotyping analyses to define Th17 cells and B cell subsets. Adult Ch22q11.2D patients had a higher percentage of IL-4+CD4+ T cells than controls. Th17 cells were no different in patients and controls. In addition, adult Ch22q11.2D syndrome patients had significantly lower switched memory B cells, suggesting a dysregulated B cell compartment. These studies demonstrate that the decrement in T cell production has secondary consequences in the immune system, which could mold the patients\u27 clinical picture

Total and specific IgE associations between New York City Head Start children and their parents.

BACKGROUND: Allergy and asthma risk share strong inherited components; however, the relative importance of maternal and paternal atopy in predicting child atopy remain unclear. OBJECTIVE: We sought to identify relationships between parents\u27 and children\u27s total and specific IgE levels within family units as predictors of allergic risk in children. METHODS: Total and allergen-specific IgE (to dust mite, cockroach, mouse, and cat) were determined by means of ImmunoCap (Phadia, Inc, Portage, Mich) in a sample of families participating in New York City Head Start programs. Regression models were developed to determine the associations of parents\u27 and children\u27s total IgE levels and sensitization patterns. RESULTS: Blood specimens were collected from 161 family triads of mother, father, and child (83 boys and 78 girls). At a mean age of 4 years, boys had significantly higher total IgE levels than girls. Boys\u27 total IgE levels were highly correlated with both mothers\u27 (P \u3c .002) and fathers\u27 (P = .002) total IgE levels; girls\u27 total IgE levels were not. Unlike total IgE levels, specific IgE levels among both boys and girls were associated with their mothers\u27 specific IgE levels. Dust mite sensitization among mothers was predictive of children\u27s sensitization to each of the 4 aeroallergens. CONCLUSION: The strong associations between parents\u27 and children\u27s IgE levels suggest that assessment of parents\u27 total and locally relevant allergen-specific IgE levels might have value in predicting atopy in children of preschool age