Approximately 25% of subjects with common variable immunodeficiency (CVID) develop autoimmune disease. We analyzed Tcell subsets, specifically regulatory Tcells along with B cell subsets to determine whether there were changes in regulatory T cells which would correlate with the autoimmune disease clinical phenotype in CVID subjects. We hypothesized that regulatory T cell (CD4+CD25hiCD127lo) suppressive function would be impaired in CVID subjects with autoimmune disease. Using purified, sorted Treg from CVID subjects (n=14) and from healthy controls (HC, n=5) in standard suppression assays, we found the suppressive function of Treg from CVID subjects with autoimmune disease (CVID w/ AI, n=8) to be significantly attenuated compared to CVID subjects with no autoimmune disease (CVID w/o AI, n=6) and to HC (n=5). A number of proteins associated with Treg function were decreased in expression as detected through immunofluorescent antibody via flow cytometry (mean fluorescence intensity (MFI) of FoxP3, Granzyme A, XCL1, pSTAT5, and GITR in Treg was significantly lower (by up to 3 fold) in CVID w/ AI compared to CVID w/o AI and HC. Furthermore, a statistically significant correlation was found between intracellular MFI of FoxP3, Granzyme A, and pSTAT5 in Treg and the degree of Treg dysfunction. These results suggest that attenuation of Treg function is associated with autoimmune disease in CVID subjects and may contribute to autoimmune pathogenesis.

Rationale: Basophils contribute to anaphylaxis and allergies. We examined the utility of assessing basophil-associated surface antigens (CD11b/CD63/CD123/CD203c/CD294) in characterizing and monitoring subjects with nut allergy. Methods: We used flow cytometry to analyze basophils at baseline (without any activation) and after ex vivo stimulation of whole blood by addition of nut or other allergens for 2, 10, and 30 min. We also evaluated whether basophil expression of CD11b/CD63/CD123/CD203c/CD294 was altered in subjects treated with anti-IgE monoclonal antibody (omalizumab) to reduce plasma levels of IgE. Results: We demonstrate that basophil CD203c levels are increased at baseline in subjects with nut allergy compared to healthy controls (13 subjects in each group, p < 0.0001). Furthermore, we confirm that significantly increased expression of CD203c occurs on subject basophils when stimulated with the allergen to which the subject is sensitive and can be detected rapidly (10 min of stimulation, n = 11, p < 0.0008). In 5 subjects with severe peanut allergy, basophil CD203c expression following stimulation with peanut allergen was significantly decreased (p < 0.05) after 4 and 8 weeks of omalizumab treatment but returned toward pretreatment levels after treatment cessation. Conclusions: Subjects with nut allergy show an increase of basophil CD203c levels at baseline and following rapid ex vivo stimulation with nut allergen. Both can be reduced by omalizumab therapy. These results highlight the potential of using basophil CD203c levels for baseline diagnosis and therapeutic monitoring in subjects with nut allergy.

Background: Peanut allergy is the leading cause of food-related anaphylaxis, and accidental exposures are common. Oral immunotherapy (OIT) has been posited as a potential treatment. Methods: Patients aged 3–65 years with peanut-specific IgE ≥7 kU/l and/or a positive skin prick test with a history of an allergic reaction to peanut were recruited to undergo an OIT protocol. All adverse reactions were recorded by research staff or patients in real time. Results: Twenty-four patients received 6,662 doses. Symptoms were mostly mild (84%), and only 3 severe gastrointestinal reactions required the administration of epinephrine. Abdominal pain was the most common reaction, followed by oropharyngeal and lip pruritus. Respiratory symptoms were rare. Conclusions: In this trial of OIT in adults and children, most reactions were mild.

Aims-To determine whether specific IgE and skin prick test correlate better in predicting reaction severity during a double-blinded placebo controlled food challenge (DBPCFC) for egg, milk, and multiple tree nut allergens.Study design-Prospective study. Methodology-We examined the reaction severity of twenty-four subjects to nine possible food allergens: milk, egg, almond, cashew, hazelnut, peanut, sesame, pecan and walnut. Specific IgE and SPT were performed before each DBPCFC. DBPCFC results were classified into mild (1), moderate (2), or severe (3) reactions using a modified Bock's criteria.Results-Twenty four subjects underwent a total of 80 DBPCFC. Eighty percent of all DBPCFCs resulted in a positive reaction. A majority, 71%, were classified as mild. No reactions occurred with a SPT of zero mm while three reactions occurred with a negative specific IgE. All reactions were reversible with medication.Conclusion-These data suggest that SPT and specific IgE levels are not associated with reaction severity (p<0.64 and 0.27, respectively). We also found that combining specific IgE and SPT improved specificity but did not help to achieve clinically useful sensitivity. For instance, an SPT > 5mm had a sensitivity of 91% and specificity of 50%. Combining SPT > 5mm and IgE > 7 resulted in a reduced sensitivity of 64%. Unexpectedly, a history of anaphylaxis 70% (n=17) was not predictive of anaphylaxis on challenge 4% (n=2).

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