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Changes in the Immune Response Induced By Sublingual Immunotherapy for Peach Allergy during One Year
Abstracts AB115
J ALLERGY CLIN IMMUNOL VOLUME 139, NUMBER 2
Atopic Disease in Primary Immune Deficiency with B Cell Dysfunction Amongst a U.S. Immunodeficiency Network (USIDNET) Cohort
Gretchen A. Harmon, MD1,2, Magee L. DeFelice, MD1,2, and Megan Morsheimer, MD, MPH1,2; 1Thomas Jefferson University Hospital, Philadelphia, PA, 2Nemours A.I. duPont Hospital for Children, Wilmington, DE. RATIONALE: Atopic disease is an important consideration in the care of patients with primary immune deficiencies (PID), however, forming the diagnosis may be challenging in patients with low or undetectable serum IgE. We aim to describe the prevalence of allergic disease in a cohort of patients with PID and B cell dysfunction, with the goal of improving recognition of such patients who may benefit from allergy treatment. METHODS: A query was submitted to the USIDNET database to examine associated conditions, allergic reactions, and use of allergen immunotherapy in patients with a diagnosis of a PID with B cell dysfunction. RESULTS: The query identified 2391 cases, the majority (63%) with a diagnosis of common variable immunodeficiency disorders with unknown genetic basis (CVID). Five patients received immunotherapy. For each PID within this cohort, allergic rhinitis and asthma were reported in the following percentages: Activated PI3Kd (0%, 0%), agammaglobulinemia of unknown cause or unlisted gene defect (10%, 20%), AID deficiency (0%, 33%), BTK deficiency (2%, 9%), CD40L deficiency (0%, 4%), CVID (5%, 29%), NEMO deficiency (11%, 26%), Hyper IgM due to uncertain or unlisted cause (<1%, 3%), hypogammaglobulinemia of unknown cause or unlisted gene defect (<1%, 28%), isolated IgG subclass deficiency (7%, 53%), selective IgA deficiency (6%, 45%), specific antibody deficiency with normal IgG concentrations and normal numbers of B cells (11%, 52%), TACI deficiency (60%, 20%), transient hypogammaglobulinemia of infancy with normal numbers of B cells (11%, 33%). CONCLUSIONS: The data suggest that atopic disease is not uncommonly seen in the setting of B cell dysfunction.
360
Th2-Related Chemokine Receptors Do Not Always Reflect Th2 Cells Under Physiological Conditions
Satoru Watanabe, MS1, Yoshiyuki Yamada2, and Hirokazu Murakami3; Gunma Children’s Medical Center, Shibukawa, Gunma, Japan; Gunma University Faculty of Medicine School of Health Science, Maebashi, Gunma, Japan, 2Gunma Children’s Medical Center, Shibukawa, Japan, 3 Gunma University Graduate School of Health Sciences, Maebashi, Japan. RATIONALE: Disruption of the balance between T-helper (Th)-1 and Th2 cells leads to various immune abnormalities. Chemokine receptors such as CCR3, CCR4, CCR7, and CCR8 and the PGD2 receptor, CRTH2, are associated with Th2. However, the distribution of these receptors on Th2 cells under physiological conditions is only partly reported as ‘‘control.’’ Indeed, the frequencies of these receptors, which indicate Th2 cell populations in those ‘‘controls,’’ vary with each study. This study was aimed at determining whether Th2-related chemokine receptors could be surface surrogate markers for cytoplasmic Th2 cytokine staining, even under physiological conditions. METHODS: With institutional review board approval, 5 healthy volunteers (2 males) without active inflammatory diseases including allergic diseases, systemic viral infections, tumors, or autoimmune diseases were enrolled. Surface (CRTH2, CCR3, CCR4, CCR7, and CCR8) and cytoplasmic (IL-4 and IL-13) molecules of CD4+ lymphocytes were analyzed by flow cytometry. We determined if cells expressing these Th2-related receptors produced Th2 cytokines. RESULTS: A significant amount of CRTH2+ cells (48.7 6 7.0%), 16.3 6 1.5% of CCR3+ cells, 13.2 6 3.8% of CCR4+ cells, 11.8 6 2.1% of CCR7+ cells, and 6.8 6 1.7% of CCR8+ cells produced Th2 cytokines. The frequencies of CRTH2 and CCR3, CCR4, CCR7, or CCR8 dual1
positive cells, among Th2 cytokine-producing cells, were 3.8 6 0.7%, 8.7 6 0.7%, 6.4 6 0.9%, and 1.6 6 0.4%, respectively. CONCLUSIONS: CCR3+, CCR4+, CCR7+, or CCR8+cells scarcely produced IL-4 and IL-13, which indicated that these receptors might not be good surrogate markers for cytoplasmic Th2 cytokines under physiological conditions.
361
Changes in the Immune Response Induced By Sublingual Immunotherapy for Peach Allergy during One Year
Maria Francisca Palomares, PhD1, Gador Bogas, MD, PhD2, Francisca Gomez, MD, PhD3, Maria Jose Rodriguez4, Ana Molina1, Miguel Gonzalez1, Maria J. Torres, MD, PhD1, and Cristobalina Mayorga, PhD5; 1Research Laboratory, IBIMA-Regional University Hospital of Malaga, Malaga, Spain, 2Allergy Unit, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain, 3Allergy Unit, IBIMARegional University Hospital of Malaga, Malaga, Spain, 4Research Laboratory-Allergy Unit, IBIMA-Regional University Hospital of Malaga UMA., Malaga, Spain, 5Research Laboratory, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain. RATIONALE: Pru p 3 is the primary sensitizer of some fruits and responsible for severe reactions in the Mediterranean area. Sublingual immunotherapy (SLIT) using peach extract enriched in Pru p 3 (Prup3enriched-SLIT) brings a new perspective to treat patients with severe reactions to peach. We evaluated the lymphocyte modulation from a Th2 pattern to a Th1/Treg profile during one year of treatment. METHODS: We studied three groups: peach allergic patients who received Prup3-enriched-SLIT for 1 year, peach allergic untreated patients and healthy controls who tolerated peach. Peripheral blood mononuclear cells obtained before treatment and at different times during SLIT were cultured with Prup3. Monocyte-derived dendritic cells (DCs) maturation and lymphocyte proliferation were assessed by flow cytometry. RESULTS: We found statistically significant differences in DCs activation and maturation between allergic patients and controls at baseline. When we analyzed the effect of Pru p 3-SLIT at different times, we found a significant reduction of activation and maturation markers at the first month of treatment that was maintained after 1 year. Concerning lymphocytes, we observed a significant decrease of effector cells and an increase in Th1, NKBright and Treg cells subpopulations. These changes were only observed in treated patients. These results were similar to those obtained in the specific proliferative response to Pru p 3 in lymphocyte subpopulations. CONCLUSIONS: Patients treated with Pru p 3-SLIT showed immunological differences compared to untreated patients from a Th2 towards a Th1/Treg response. These changes could be used as biomarkers of therapy evolution during SLIT.
SUNDAY
359
J ALLERGY CLIN IMMUNOL VOLUME 139, NUMBER 2
Atopic Disease in Primary Immune Deficiency with B Cell Dysfunction Amongst a U.S. Immunodeficiency Network (USIDNET) Cohort
Gretchen A. Harmon, MD1,2, Magee L. DeFelice, MD1,2, and Megan Morsheimer, MD, MPH1,2; 1Thomas Jefferson University Hospital, Philadelphia, PA, 2Nemours A.I. duPont Hospital for Children, Wilmington, DE. RATIONALE: Atopic disease is an important consideration in the care of patients with primary immune deficiencies (PID), however, forming the diagnosis may be challenging in patients with low or undetectable serum IgE. We aim to describe the prevalence of allergic disease in a cohort of patients with PID and B cell dysfunction, with the goal of improving recognition of such patients who may benefit from allergy treatment. METHODS: A query was submitted to the USIDNET database to examine associated conditions, allergic reactions, and use of allergen immunotherapy in patients with a diagnosis of a PID with B cell dysfunction. RESULTS: The query identified 2391 cases, the majority (63%) with a diagnosis of common variable immunodeficiency disorders with unknown genetic basis (CVID). Five patients received immunotherapy. For each PID within this cohort, allergic rhinitis and asthma were reported in the following percentages: Activated PI3Kd (0%, 0%), agammaglobulinemia of unknown cause or unlisted gene defect (10%, 20%), AID deficiency (0%, 33%), BTK deficiency (2%, 9%), CD40L deficiency (0%, 4%), CVID (5%, 29%), NEMO deficiency (11%, 26%), Hyper IgM due to uncertain or unlisted cause (<1%, 3%), hypogammaglobulinemia of unknown cause or unlisted gene defect (<1%, 28%), isolated IgG subclass deficiency (7%, 53%), selective IgA deficiency (6%, 45%), specific antibody deficiency with normal IgG concentrations and normal numbers of B cells (11%, 52%), TACI deficiency (60%, 20%), transient hypogammaglobulinemia of infancy with normal numbers of B cells (11%, 33%). CONCLUSIONS: The data suggest that atopic disease is not uncommonly seen in the setting of B cell dysfunction.
360
Th2-Related Chemokine Receptors Do Not Always Reflect Th2 Cells Under Physiological Conditions
Satoru Watanabe, MS1, Yoshiyuki Yamada2, and Hirokazu Murakami3; Gunma Children’s Medical Center, Shibukawa, Gunma, Japan; Gunma University Faculty of Medicine School of Health Science, Maebashi, Gunma, Japan, 2Gunma Children’s Medical Center, Shibukawa, Japan, 3 Gunma University Graduate School of Health Sciences, Maebashi, Japan. RATIONALE: Disruption of the balance between T-helper (Th)-1 and Th2 cells leads to various immune abnormalities. Chemokine receptors such as CCR3, CCR4, CCR7, and CCR8 and the PGD2 receptor, CRTH2, are associated with Th2. However, the distribution of these receptors on Th2 cells under physiological conditions is only partly reported as ‘‘control.’’ Indeed, the frequencies of these receptors, which indicate Th2 cell populations in those ‘‘controls,’’ vary with each study. This study was aimed at determining whether Th2-related chemokine receptors could be surface surrogate markers for cytoplasmic Th2 cytokine staining, even under physiological conditions. METHODS: With institutional review board approval, 5 healthy volunteers (2 males) without active inflammatory diseases including allergic diseases, systemic viral infections, tumors, or autoimmune diseases were enrolled. Surface (CRTH2, CCR3, CCR4, CCR7, and CCR8) and cytoplasmic (IL-4 and IL-13) molecules of CD4+ lymphocytes were analyzed by flow cytometry. We determined if cells expressing these Th2-related receptors produced Th2 cytokines. RESULTS: A significant amount of CRTH2+ cells (48.7 6 7.0%), 16.3 6 1.5% of CCR3+ cells, 13.2 6 3.8% of CCR4+ cells, 11.8 6 2.1% of CCR7+ cells, and 6.8 6 1.7% of CCR8+ cells produced Th2 cytokines. The frequencies of CRTH2 and CCR3, CCR4, CCR7, or CCR8 dual1
positive cells, among Th2 cytokine-producing cells, were 3.8 6 0.7%, 8.7 6 0.7%, 6.4 6 0.9%, and 1.6 6 0.4%, respectively. CONCLUSIONS: CCR3+, CCR4+, CCR7+, or CCR8+cells scarcely produced IL-4 and IL-13, which indicated that these receptors might not be good surrogate markers for cytoplasmic Th2 cytokines under physiological conditions.
361
Changes in the Immune Response Induced By Sublingual Immunotherapy for Peach Allergy during One Year
Maria Francisca Palomares, PhD1, Gador Bogas, MD, PhD2, Francisca Gomez, MD, PhD3, Maria Jose Rodriguez4, Ana Molina1, Miguel Gonzalez1, Maria J. Torres, MD, PhD1, and Cristobalina Mayorga, PhD5; 1Research Laboratory, IBIMA-Regional University Hospital of Malaga, Malaga, Spain, 2Allergy Unit, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain, 3Allergy Unit, IBIMARegional University Hospital of Malaga, Malaga, Spain, 4Research Laboratory-Allergy Unit, IBIMA-Regional University Hospital of Malaga UMA., Malaga, Spain, 5Research Laboratory, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain. RATIONALE: Pru p 3 is the primary sensitizer of some fruits and responsible for severe reactions in the Mediterranean area. Sublingual immunotherapy (SLIT) using peach extract enriched in Pru p 3 (Prup3enriched-SLIT) brings a new perspective to treat patients with severe reactions to peach. We evaluated the lymphocyte modulation from a Th2 pattern to a Th1/Treg profile during one year of treatment. METHODS: We studied three groups: peach allergic patients who received Prup3-enriched-SLIT for 1 year, peach allergic untreated patients and healthy controls who tolerated peach. Peripheral blood mononuclear cells obtained before treatment and at different times during SLIT were cultured with Prup3. Monocyte-derived dendritic cells (DCs) maturation and lymphocyte proliferation were assessed by flow cytometry. RESULTS: We found statistically significant differences in DCs activation and maturation between allergic patients and controls at baseline. When we analyzed the effect of Pru p 3-SLIT at different times, we found a significant reduction of activation and maturation markers at the first month of treatment that was maintained after 1 year. Concerning lymphocytes, we observed a significant decrease of effector cells and an increase in Th1, NKBright and Treg cells subpopulations. These changes were only observed in treated patients. These results were similar to those obtained in the specific proliferative response to Pru p 3 in lymphocyte subpopulations. CONCLUSIONS: Patients treated with Pru p 3-SLIT showed immunological differences compared to untreated patients from a Th2 towards a Th1/Treg response. These changes could be used as biomarkers of therapy evolution during SLIT.
SUNDAY
359