The Differential Relationship Between Regulatory T-Cells and
Age in Children with Food Allergy Benjamin T. Prince, MD1, Kristin A. Erickson1, Christine Szychlinski, MS, APN, CPNP2, Robert P. Schleimer, PhD, FAAAAI3, Paul Bryce, PhD3, Anne Marie Singh, MD1,2; 1Division of Allergy-Immunology, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, 2Division of Allergy-Immunology, Department of Pediatrics, Ann & Robert H. Lurie Childrens Hospital of Chicago, Chicago, IL, 3Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL. RATIONALE: Regulatory T (Treg) cells are well known to play an important role in the maintenance of self-tolerance, and patients who lack these cells, such as in IPEX syndrome, have an increased incidence of allergic disease. Although studies have highlighted differences in peripheral blood Treg populations of atopic adults, only a few conflicting studies have examined differences in Tregs among children with allergic diseases. METHODS: Peripheral blood mononuclear cells were isolated from 47 patients (0-18yrs) and analyzed using flow cytometry for CD3, CD4, CD25, CD127, CCR6, and Foxp3. Populations of Tregs, defined as CD4+CD25hiCD127loFoxp3+, were compared in food allergic children and healthy controls using a 2-tailed Students t-test and linear regression modeling. _6yrs had significantly lower percentRESULTS: Food allergic children < ages (p<0.05) of Tregs compared to healthy controls of similar age. This difference was not observed in older children. There was a significant decrease in both Treg cell percentages (p50.018, R50.584) and Treg expression of Foxp3 (p50.012, R50.613) with age in healthy controls but not in children with food allergy. Finally, food allergic children >6yrs had significantly less Tregs expressing CCR6 (p<0.05), a gut-homing marker, and this cell population significantly increased with age (p50.013, R50.626) in healthy controls but not food allergic children. CONCLUSIONS: Younger, food allergic children had significantly lower percentages of Tregs compared to healthy controls, and this difference did not persist with older children. This supports the hypothesis that early childhood is likely a critical time in the development of normal immune regulation and that Tregs are important in this process.
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Glutathione S-Transferase Mu 1 (GSTM1) Gene Associated with
Allergic Rhinitis in a Food Allergy Cohort Sheva K. Chervinskiy, DO1, Lisa Smeester2, Michael D. Kulis, Jr, PhD3, David B. Peden, MD, MS, FAAAAI4, Brian P. Vickery, MD5, Rebecca C. Fry, PhD6; 1Department of Pediatrics, University of North Carolina, Chapel Hill, NC, 2Gillings School of Public Health, University of North Carolina, Chapel Hill, NC, 3University of North Carolina School of Medicine, Chapel Hill, NC, 4Office #544, Campus Box 7310, University of North Carolina at Chapel Hill School Medicine, NC, 5Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina, USA, 6 Gillings School of Public Health, University of North Carolina, Chapel Hill NC. RATIONALE: GSTM1 genes have been implicated in atopic inflammatory diseases. In this study, we explored whether GSTM1 genotype was associated with food allergy phenotypes. METHODS: Biospecimens from 100 randomly sampled food allergy research subjects were collected for gene analysis. GSTM1 gene analysis was carried out as previously described. We conducted a retrospective chart review to collect phenotypic information, including past medical history, number of allergic foods, serum specific IgE and food allergy treatment response. Mann-Whitney and Chi-square analysis was performed. RESULTS: Of the 100 samples obtained, 81 subjects were successfully genotyped, and 48/81 (x %) had a null GSTM1 genotype. Of the genotyped subjects, 68 were successfully phenotyped via chart review. GSTM1 status had no significant association with specific IgE, number of food allergies, or response to food allergy treatment, as measured by food challenge outcomes. There was no statistically significant association between
J ALLERGY CLIN IMMUNOL
FEBRUARY 2015
GSTM1 genotype with reported history of asthma or atopic dermatitis.
We found that patients with a GSTM1 genotype had a statistically significant association with the incidence of allergic rhinitis in in this cohort (p5 0.03). CONCLUSIONS: In this cohort of food allergy patients, allergic rhinitis was significantly associated with the GSTM1 genotype. This supports previous studies revealing the association of this gene with allergic airway disease. GSTM1 did not impact food allergy phenotype nor treatment response to food allergy desensitization.
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Disseminated Atypical Mycobacterial Infection in Three
Patients with Complete Digeorge Anomaly Noah O. Agada, MD1, Suellen M. Yin, MD2, Jonathan S. Tam, MD2, Matthew S. Kelly, MD1, M. Louise Markert, MD, PhD, FAAAAI1; 1 Duke University Medical Center, Durham, NC, 2Childrens Hospital Los Angeles, Los Angeles, CA. RATIONALE: Complete DiGeorge anomaly is a primary immunodeficiency characterized by athymia with fewer than 50 nave T cells/mm3 associated with either a cardiac defect or hypoparathyroidism. Disseminated mycobacterial infection has not been described in these patients. We present three cases of disseminated atypical mycobacterial infection that developed among children with complete DiGeorge anomaly. METHODS: Clinical, laboratory, immunologic and radiologic data of patients with complete DiGeorge anomaly referred to Duke University for transplant were reviewed. RESULTS: In patient 1 (P1), the diagnosis of disseminated mycobacterium avium complex (MAC) was made by lung biopsy 4 months after thymus transplantation after a mass was noted on chest CT obtained to evaluate for a source of fevers. P2 was diagnosed with MAC 2.4 months after thymus transplantation from a mycobacterial blood culture obtained for persistent fever. P2 was given steroids for possible immune reconstitution inflammatory syndrome when fevers recurred 18 days after starting anti-mycobacterial therapy. In P3, a chest CT obtained to evaluate fevers revealed lymphadenopathy and mycobacterial culture of a thoracic lymph node biopsy grew Mycobacterium kansasii. P1 is on enteral medications for MAC at 22 months post-transplantation and has normal T cell numbers. P2 died 5 months after transplantation with finding of disseminated MAC on autopsy. Flow cytometry revealed nave T cell development; the autopsy showed thymopoiesis. P3 is 3 months post-transplantation, remains on anti-mycobacterial treatment, and has not yet developed nave T cells. CONCLUSIONS: Azithromycin or clarithromycin prophylaxis should be considered for patients with complete DiGeorge anomaly. Aggressive antimycobacterial therapy without steroids is recommended.