Faculty Bibliography

BACKGROUND & AIMS/OBJECTIVE:Secreted immunoglobulins play an integral role in host defense at mucosal surfaces, and recent evidence shows that IgG can participate in antigen sampling from the intestinal lumen. We examined whether IgE also could facilitate transepithelial antigen sampling. METHODS:Stool samples from food-allergic patients undergoing oral food challenge were analyzed for CD23 and food-specific IgE. CD23 isoform expression on primary human intestinal epithelial cells (IEC) was analyzed by polymerase chain reaction. The role of CD23 isoforms in transcytosis of antigen and IgE-antigen complexes was assessed using polarized human T84 cells retrovirally transfected with CD23a or CD23b. RESULTS:CD23 was expressed constitutively on IECs, and food-allergic patients had increased levels of soluble CD23 and food-specific IgE in the stool after challenge. CD23a, but not CD23b, was expressed by primary human IECs. We show in transcytosis assays that CD23a, but not CD23b, acts as a bidirectional transporter of IgE. In addition, specific IgE facilitated the uptake of antigen from the apical surface of an epithelial monolayer by diverting antigen from delivery to lysosomes. Finally, delivery of antigen-IgE complexes across the epithelial barrier could induce the degranulation of rat basophil leukemia cells transfected with the human high-affinity IgE receptor. CONCLUSIONS:These studies show that CD23a is expressed normally on human IECs, and in the presence of IgE can function as an antigen-sampling mechanism capable of activating subepithelial mast cells. IgE may serve as a secretory immunoglobulin that in concert with CD23 participates in food-induced pathophysiology of the gastrointestinal tract.

BACKGROUND:Levels of IgE antibody to egg white of greater than 7 kIU/L are highly predictive of clinical reactivity to egg, and lower levels often require evaluation with oral food challenge (OFC) to establish definitive diagnosis. OFCs have inherent risks, and diagnostic criteria indicating high likelihood of passing would be clinically useful. OBJECTIVE:We sought to determine whether the size of the skin prick test (SPT) to egg white adds diagnostic utility for children with low egg white-specific IgE antibody levels. METHODS:A retrospective analysis of clinical history, egg white-specific IgE antibody levels, SPT responses, and egg OFC outcomes was performed. RESULTS:Children who passed (n = 29) egg OFCs and those who failed (n = 45) did not differ significantly in age, clinical characteristics, or egg white-specific IgE levels. There were, however, significant differences between both egg white SPT wheal response size and egg/histamine SPT wheal index. Children who failed egg OFCs had a median wheal of 5.0 mm; those who passed had a median wheal of 3.0 mm (P = .003). Children who failed egg OFCs had a median egg/histamine index of 1.00; those who passed had a median index of 0.71 (P = .001). For egg white-specific IgE levels of less than 2.5 kIU/L, an SPT wheal of 3 mm or an egg/histamine index of 0.65 was associated with a 50% chance of passing. CONCLUSION/CONCLUSIONS:In children with low egg white-specific IgE levels, those with smaller SPT wheal responses to egg were more likely to pass an egg OFC than those with larger wheal responses. The size of the egg white SPT response might provide additional information to determine the timing of egg OFC. CLINICAL IMPLICATIONS/CONCLUSIONS:The size of the egg white SPT wheal response might provide the clinician with additional information to determine the timing of egg OFC in children with low egg white-specific IgE antibody levels.

Food allergy encompasses a variety of immune-mediated adverse reactions to foods. IgE-mediated, cell-mediated, and mixed-mechanism food allergy disorders are recognized. Over the past 2 decades, the prevalence of food allergy doubled and its phenotypic expression increased in Westernized societies. Major food allergens have been identified for many common foods. Laboratory diagnosis of food allergy relies heavily on the detection of food-specific IgE antibodies, but novel approaches include tests for T-cell-mediated disorders and tests for prediction of tolerance. OFC remains the diagnostic standard for food allergy. Management of food allergy focuses on avoidance of the offending foods, nutritional support, and prompt recognition and treatment of acute food allergic reactions. Anti-IgE monoclonal antibody is the first potential therapy for food allergy that is under-going testing in clinical trials.

The past two decades have witnessed an increase in prevalence of food allergy that has been matched with a tremendous progress in research that has led to better understanding of pathogenic mechanisms and development of novel therapies for food allergy. Establishment of murine models of peanut and cow's milk allergy has been extremely useful in investigating food allergy treatments. Diverse strategies for prevention and treatment of established food allergy are being evaluated. Anti-IgE antibody therapy, Chinese herbal medicines, and killed bacteria expressing modified major peanut allergens represent the most promising approaches that will lead to development of therapy for patients for whom no effective treatment is currently available.

Novel approaches to the treatment and prevention of IgE-mediated food allergy include anti-IgE, food allergy vaccines, herbal preparations, and probiotics. They bring real hope to the patients for whom no specific therapy is available. These immunomodulatory therapies have to be evaluated carefully for potential side effects, such as overstimulation of T helper cell type 1 immune antibodies. Animal models of food allergy are invaluable in testing new therapies for food allergy.

OBJECTIVE:To characterize the immunodeficiency in ataxia-telangiectasia (A-T) and to determine whether the immunodeficiency is progressive and associated with increased susceptibility to infections. STUDY DESIGN/METHODS:Records of 100 consecutive patients with A-T from the Johns Hopkins Ataxia-Telangiectasia Clinical Center (ATCC) were reviewed. RESULTS:Immunoglobulin (Ig) deficiencies are common, affecting IgG4 in 65% of patients, IgA in 63%, IgG2 in 48%, IgE in 23%, and IgG in 18%. Lymphopenia affected 71% of patients, with reduced B-lymphocyte number in 75%, CD4 T lymphocytes in 69%, and CD8 T lymphocytes in 51%. There was no trend for increased frequency or severity of immune abnormalities with age. Recurrent upper and lower respiratory tract infections were frequent: otitis media in 46% of patients, sinusitis in 27%, bronchitis in 19%, and pneumonia in 15%. Sepsis occurred in 5 patients, in 2 patients concurrent with cancer chemotherapy. Warts affected 17% of patients, herpes simplex 8%, molluscum contagiosum 5%, candidal esophagitis 3%, and herpes zoster 2%. Uncomplicated varicella infection occurred in 44% of patients; 2 patients had more than one clinical episode. No patient had Pneumocystis jerovici pneumonia or a complication of live viral vaccine. CONCLUSIONS:In spite of the high prevalence of laboratory immunologic abnormalities, systemic bacterial, severe viral, and opportunistic infections are uncommon in A-T. Cross-sectional analysis suggests that the immune defect is rarely progressive.