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IgE Antibodies to Fungi Among Asthmatic Children Living in Homes Damaged By Hurricane Sandy in New York City
AB180 Abstracts
589
Extra-Immunologic Manifestations of Common Variable Immunodeficiency in Pediatric Versus Adult Patients
SUNDAY
Lauren A. Sanchez, MD, MA1, Matthew S. Pantell, MD, MS2, Solrun Melkorka Maggadottir, MD1, Kathleen E. Sullivan, MD, PhD, FAAAAI3USIDNet4. 1Children’s Hospital of Philadelphia, Philadelphia, PA, 2University of California, San Francisco, San Francisco, CA, 3The Children’s Hospital of Philadelphia, Philadelphia, PA, 4U.S. Immunodeficiency Network. RATIONALE: Common variable immunodeficiency (CVID) is a primary immunodeficiency defined by hypogammaglobulinemia, poor antibody response to vaccinations, and frequent or chronic bacterial infections. CVID has also been associated with autoimmunity, increased risk of lymphoid malignancy, enteropathy/colitis, and granulomatous disease. We sought to define other extra-immunologic manifestations in pediatric and adult patients with CVID. METHODS: We utilized retrospective data made available from the United States Immunodeficiency Network (USIDNET). 231 pediatric _18 years old) were _17 years old) and 339 adult patients (i.e. > patients (i.e. < identified in USIDNET with a diagnosis of CVID, and had at least one documented clinical condition. Chi-squared testing was used to compare conditions between pediatric and adult patients. RESULTS: Frequently reported extraimmunologic manifestations in both pediatric and adult CVID patients included non-infectious diarrhea (22.51% vs 28.61%, respectively), fatigue (30.74% vs 38.64%), gastroesophageal reflux disease (17.75% vs 23.01%) and headaches (8.23% vs 14.75%). Frequently reported conditions with clinically significant (p <0.05) enrichment in adult CVID patients included aches/chronic pain (9.52% vs 23.60%, p<0.001), arthralgia (10.82% vs 17.99%, p50.019), anxiety (1.73% vs 5.31%, p50.029), depression (6.49% vs 22.42%, p<0.001), hypothyroidism (3.03% vs 10.91%, p50.001), nonlymphoid malignancy (2.60% vs 11.50%, p<0.001) and osteopenia (2.60% vs 7.96%, p50.007). CONCLUSIONS: Chronic pain (‘‘aches’’ and arthralgia), anxiety, and depression are underappreciated but frequently reported co-morbid conditions in CVID. Regular screening for depression and anxiety in adult CVID patients may be justified. Further research may be warranted to understand how best to provide psychosocial supports to both pediatric and adult patients with CVID.
590
Role of B Cell Activating Factor in CVID Lung Disease
Paul J. Maglione, MD, PhD1, Montserrat Cols2, Emma Roellke2, Lin Radigan2, Charlotte Cunningham-Rundles, MD, PhD2; 1Clinical Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, 2Icahn School of Medicine at Mount Sinai, New York, NY. RATIONALE: Common variable immunodeficiency (CVID) is complicated by interstitial lung disease (ILD) in a subset of patients, which can worsen morbidity and mortality. While the specific biochemical mechanisms driving CVID ILD are not known, pulmonary pathology is characterized by profound lymphoid hyperplasia. As CVID patients have elevated serum levels of B cell activating factor (BAFF) and transgenic overexpression of BAFF causes lymphoid hyperplasia in mice, we looked for evidence of BAFF expression and signaling in CVID ILD. METHODS: Clinical history, conventional laboratory test results, and pulmonary function were obtained from the medical record. Levels of a proliferation-inducing ligand (APRIL) and BAFF were measured in serum and cell culture supernatants by enzyme-linked immunosorbent assay (ELISA). Immunofluorescence and immunohistochemistry was used to localize leukocytes as well as BAFF, BAFF-R, and Bcl-2 in lung biopsies from patients with CVID ILD. Approval of the institutional review board was obtained. RESULTS: While markers of lymphoid hyperplasia inversely correlated with APRIL, serum levels of BAFF remained elevated in all patients.
J ALLERGY CLIN IMMUNOL FEBRUARY 2016
Peripheral blood monocytes from CVID patients produced significantly higher levels of BAFF than controls. BAFF was expressed in CVID lungs, exclusively localized with innate immune cells. BAFF receptor (BAFF-R) expression was limited to ectopic pulmonary B cell follicles and corresponded with Bcl-2, an anti-apoptotic protein downstream of BAFF-R. CONCLUSIONS: BAFF production is dysregulated in CVID - it remains elevated in patients with lymphoid hyperplasia and is produced at higher levels in culture. BAFF, BAFF-R, and Bcl-2 localize to ectopic pulmonary follicles in CVID ILD and may contribute to disease progression.
591
IgE Antibodies to Fungi Among Asthmatic Children Living in Homes Damaged By Hurricane Sandy in New York City
Adnan Divjan, BA1, Luis M. Acosta, MD2, Edward Sobek, PhD3, Nitzan Soffer, PhD2, Matthew S. Perzanowski, PhD4; 1Columbia University Mailman School of Public Health, New York, NY, 2Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, 3Assured Bio Labs, Oak Ridge, TN, 4Department of Environmental Health Sciences, Columbia University, New York, NY. RATIONALE: In New York City (NYC), domestic mold contamination was the most common residential complaint following Hurricane Sandy (HS). The purpose of this study was to evaluate the prevalence of fungal sensitization in NYC asthmatic children that were impacted by HS. METHODS: Asthmatic children (n558) living in homes damaged by HS were recruited (ages 6-15 years). Dust was collected from homes and serum from children 16-33 months after HS. Bedroom floor dust was analyzed by quantitative polymerase chain reaction for 36 fungi (Environmental Relative Moldiness Index panel) and compared to results from non-damaged homes (NYC Neighborhood Asthma and Allergy Study, n5347). IgE was measured by CAP (ThermoFisher, >0.1 IU/ml considered positive) to common fungi and those selected based on fungi detected in dust in HS damaged homes. RESULTS: As compared to non-damaged homes, significantly (P<0.05) more HS damaged homes had measurable Acremonium strictum, Aspergillus fumigatus, Aspergillus niger, Aspergillus penicillioides, Cladosporium cladosporioides, Epicoccum nigrum, Mucor amphibiorum, Penicillium purpogenum, and Scopulariopsis brevicaulis. Nearly all homes (damaged and non-damaged) had detectable levels of Aureobasidium pullulans and Cladosporium herbarum. Many (50%) of the children in HS damaged homes had measureable IgE to at least one of the fungi tested, most commonly, Alternaria alternata (36%), Candida albicans (22%) Aureobasidium pullulans (19%), Aspergillus fumigatus (17%), Helminthosporium halodes (17%) and Mucor racemosus (17%). CONCLUSIONS: Among asthmatic children living in NYC homes damaged by HS, sensitization to fungi was common, including to some species that were more abundant in HS damaged homes, suggesting that these children were susceptible to greater asthma morbidity.
589
Extra-Immunologic Manifestations of Common Variable Immunodeficiency in Pediatric Versus Adult Patients
SUNDAY
Lauren A. Sanchez, MD, MA1, Matthew S. Pantell, MD, MS2, Solrun Melkorka Maggadottir, MD1, Kathleen E. Sullivan, MD, PhD, FAAAAI3USIDNet4. 1Children’s Hospital of Philadelphia, Philadelphia, PA, 2University of California, San Francisco, San Francisco, CA, 3The Children’s Hospital of Philadelphia, Philadelphia, PA, 4U.S. Immunodeficiency Network. RATIONALE: Common variable immunodeficiency (CVID) is a primary immunodeficiency defined by hypogammaglobulinemia, poor antibody response to vaccinations, and frequent or chronic bacterial infections. CVID has also been associated with autoimmunity, increased risk of lymphoid malignancy, enteropathy/colitis, and granulomatous disease. We sought to define other extra-immunologic manifestations in pediatric and adult patients with CVID. METHODS: We utilized retrospective data made available from the United States Immunodeficiency Network (USIDNET). 231 pediatric _18 years old) were _17 years old) and 339 adult patients (i.e. > patients (i.e. < identified in USIDNET with a diagnosis of CVID, and had at least one documented clinical condition. Chi-squared testing was used to compare conditions between pediatric and adult patients. RESULTS: Frequently reported extraimmunologic manifestations in both pediatric and adult CVID patients included non-infectious diarrhea (22.51% vs 28.61%, respectively), fatigue (30.74% vs 38.64%), gastroesophageal reflux disease (17.75% vs 23.01%) and headaches (8.23% vs 14.75%). Frequently reported conditions with clinically significant (p <0.05) enrichment in adult CVID patients included aches/chronic pain (9.52% vs 23.60%, p<0.001), arthralgia (10.82% vs 17.99%, p50.019), anxiety (1.73% vs 5.31%, p50.029), depression (6.49% vs 22.42%, p<0.001), hypothyroidism (3.03% vs 10.91%, p50.001), nonlymphoid malignancy (2.60% vs 11.50%, p<0.001) and osteopenia (2.60% vs 7.96%, p50.007). CONCLUSIONS: Chronic pain (‘‘aches’’ and arthralgia), anxiety, and depression are underappreciated but frequently reported co-morbid conditions in CVID. Regular screening for depression and anxiety in adult CVID patients may be justified. Further research may be warranted to understand how best to provide psychosocial supports to both pediatric and adult patients with CVID.
590
Role of B Cell Activating Factor in CVID Lung Disease
Paul J. Maglione, MD, PhD1, Montserrat Cols2, Emma Roellke2, Lin Radigan2, Charlotte Cunningham-Rundles, MD, PhD2; 1Clinical Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, 2Icahn School of Medicine at Mount Sinai, New York, NY. RATIONALE: Common variable immunodeficiency (CVID) is complicated by interstitial lung disease (ILD) in a subset of patients, which can worsen morbidity and mortality. While the specific biochemical mechanisms driving CVID ILD are not known, pulmonary pathology is characterized by profound lymphoid hyperplasia. As CVID patients have elevated serum levels of B cell activating factor (BAFF) and transgenic overexpression of BAFF causes lymphoid hyperplasia in mice, we looked for evidence of BAFF expression and signaling in CVID ILD. METHODS: Clinical history, conventional laboratory test results, and pulmonary function were obtained from the medical record. Levels of a proliferation-inducing ligand (APRIL) and BAFF were measured in serum and cell culture supernatants by enzyme-linked immunosorbent assay (ELISA). Immunofluorescence and immunohistochemistry was used to localize leukocytes as well as BAFF, BAFF-R, and Bcl-2 in lung biopsies from patients with CVID ILD. Approval of the institutional review board was obtained. RESULTS: While markers of lymphoid hyperplasia inversely correlated with APRIL, serum levels of BAFF remained elevated in all patients.
J ALLERGY CLIN IMMUNOL FEBRUARY 2016
Peripheral blood monocytes from CVID patients produced significantly higher levels of BAFF than controls. BAFF was expressed in CVID lungs, exclusively localized with innate immune cells. BAFF receptor (BAFF-R) expression was limited to ectopic pulmonary B cell follicles and corresponded with Bcl-2, an anti-apoptotic protein downstream of BAFF-R. CONCLUSIONS: BAFF production is dysregulated in CVID - it remains elevated in patients with lymphoid hyperplasia and is produced at higher levels in culture. BAFF, BAFF-R, and Bcl-2 localize to ectopic pulmonary follicles in CVID ILD and may contribute to disease progression.
591
IgE Antibodies to Fungi Among Asthmatic Children Living in Homes Damaged By Hurricane Sandy in New York City
Adnan Divjan, BA1, Luis M. Acosta, MD2, Edward Sobek, PhD3, Nitzan Soffer, PhD2, Matthew S. Perzanowski, PhD4; 1Columbia University Mailman School of Public Health, New York, NY, 2Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, 3Assured Bio Labs, Oak Ridge, TN, 4Department of Environmental Health Sciences, Columbia University, New York, NY. RATIONALE: In New York City (NYC), domestic mold contamination was the most common residential complaint following Hurricane Sandy (HS). The purpose of this study was to evaluate the prevalence of fungal sensitization in NYC asthmatic children that were impacted by HS. METHODS: Asthmatic children (n558) living in homes damaged by HS were recruited (ages 6-15 years). Dust was collected from homes and serum from children 16-33 months after HS. Bedroom floor dust was analyzed by quantitative polymerase chain reaction for 36 fungi (Environmental Relative Moldiness Index panel) and compared to results from non-damaged homes (NYC Neighborhood Asthma and Allergy Study, n5347). IgE was measured by CAP (ThermoFisher, >0.1 IU/ml considered positive) to common fungi and those selected based on fungi detected in dust in HS damaged homes. RESULTS: As compared to non-damaged homes, significantly (P<0.05) more HS damaged homes had measurable Acremonium strictum, Aspergillus fumigatus, Aspergillus niger, Aspergillus penicillioides, Cladosporium cladosporioides, Epicoccum nigrum, Mucor amphibiorum, Penicillium purpogenum, and Scopulariopsis brevicaulis. Nearly all homes (damaged and non-damaged) had detectable levels of Aureobasidium pullulans and Cladosporium herbarum. Many (50%) of the children in HS damaged homes had measureable IgE to at least one of the fungi tested, most commonly, Alternaria alternata (36%), Candida albicans (22%) Aureobasidium pullulans (19%), Aspergillus fumigatus (17%), Helminthosporium halodes (17%) and Mucor racemosus (17%). CONCLUSIONS: Among asthmatic children living in NYC homes damaged by HS, sensitization to fungi was common, including to some species that were more abundant in HS damaged homes, suggesting that these children were susceptible to greater asthma morbidity.