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Clinical and Molecular Allergy - Latest articles
Differential response of human basophil activation markers: a multi-parameter flow cytometry approach
Salvatore Chirumbolo, Antonio Vella, Riccardo Ortolani, Marzia De Gironcoli, Pietro Solero, Giuseppe Tridente and Paolo Bellavite Thu, 16 Oct 2008 00:00:00 -0000
Background: Basophils are circulating cells involved in hypersensitivity reactions and allergy but many aspects of their activation, including the sensitivity to external triggering factors and the molecular aspects of cell responses, are still to be focused. In this context, polychromatic flow cytometry (PFC) is a proper tool to investigate basophil function, as it allows to distinguish the expression of several membrane markers upon activation in multiple experimental conditions. Methods: Cell suspensions were prepared from leukocyte buffy coat of K2-EDTA anticoagulated blood specimens; about 1500-2500 cellular events for each tested sample, gated in the lymphocyte CD45dim area and then electronically purified as HLADRnon expressing/CD123bright, were identified as basophilic cells. Basophil activation with fMLP, anti-IgE and calcium ionophore A23187 was evaluated by studying up-regulation of the indicated membrane markers with a two-laser six-color PFC protocol. Results: Following stimulation, CD63, CD13, CD45 and the ectoenzyme CD203c up-regulated their membrane expression, while CD69 did not; CD63 expression occurred immediately (within 60 sec) but only in a minority of basophils, even at optimal agonist doses (in 33% and 14% of basophils, following fMLP and anti-IgE stimulation respectively). CD203c up-regulation occurred in the whole basophil population, even in CD63non expressing cells. Dose-dependence curves revealed CD203c as a more sensitive marker than CD63, in response to fMLP but not in response to anti-IgE and to calcium ionophore. Conclusion: Use of polychromatic flow cytometry allowed efficient basophil electronic purification and identification of different behaviors of the major activation markers. The simultaneous use of two markers of activation and careful choice of activator are essential steps for reliable assessment of human basophil functions.
Diversity of the gut microbiota and eczema in early life
Erick Forno, Andrew B Onderdonk, John McCracken, Augusto A Litonjua, Daniel Laskey, Mary L Delaney, Andrea M DuBois, Diane R Gold, Louise M Ryan, Scott T Weiss and Juan C Celedón Mon, 22 Sep 2008 00:00:00 -0000
Background: A modest number of prospective studies of the composition of the intestinal microbiota and eczema in early life have yielded conflicting results.ObjectiveTo examine the relationship between the bacterial diversity of the gut and the development of eczema in early life by methods other than stool culture. Methods: Fecal samples were collected from 21 infants at 1 and 4 months of life. Nine infants were diagnosed with eczema by the age of 6 months (cases) and 12 infants were not (controls). After conducting denaturating gradient gel electrophoresis (DGGE) of stool samples, we compared the microbial diversity of cases and controls using the number of electrophoretic bands and the Shannon index of diversity (H') as indicators. Results: Control subjects had significantly greater fecal microbial diversity than children with eczema at ages 1 (mean H' for controls = 0.75 vs. 0.53 for cases, P = 0.01) and 4 months (mean H' for controls = 0.92 vs. 0.59 for cases, P = 0.02). The increase in diversity from 1 to 4 months of age was significant in controls (P = 0.04) but not in children who developed eczema by 6 months of age (P = 0.32). Conclusion: Our findings suggest that reduced microbial diversity is associated with the development of eczema in early life.
CpG Immunotherapy in Chenopodium album sensitized mice: The comparison of IFN-gamma, IL-10 and IgE responses in intranasal and subcutaneous administrations
Tahereh Mousavi, Nader Tajik, Maziar Moradi and Masoomeh Fallah Radjabzadeh Wed, 17 Sep 2008 00:00:00 -0000
Background: Mucosal-based immunotherapy has been already used as an alternative form of allergen delivery. In asthma, the poor success rate of immune modulation could be a consequence of inadequate immune modulation in the airways. Previously, we have found that subcutaneous (S.C) co-administration of a homemade allergenic extract from Chenopodium album (Ch.a) pollen and Guanine-Cytosine containing deoxynucleotides (CpG-ODNs) is effective to prevent the inflammatory responses in mouse. In this study we used CpG/Ch.a for immunotherapy of Ch.a-induced asthma and compared the intranasal (I.N) and S.C routes of administration concerning IFN-γ, IL-10 and total IgE responses. Methods: Ch.a sensitized mice were treated intranasaly or subcutaneously using CpG and Ch.a. extract. IFN-γ, IL-10 and total IgE were measured in supernatant culture of splenocytes and bronchoalveolor lavage (BAL) fluids by ELISA. Student's t test was used in the analysis of the results obtained from the test and control mice. Results: We found that I.N administration of CpG/Ch.a in sensitized mice significantly increased the production of systemic and mucosal IFN-γ and IL-10 compared to phosphate buffered saline (PBS), Ch.a alone and control ODNs treated sensitized mice (P ≤ 0.001). On the other hand, S.C. route induced the systemic and mucosal IFN-γ in the lower levels than in I.N one, and failed to increase systemic IL-10 induction (P = 0.06). Total serum IgE in CpG/Ch.a treated mice in both routes showed significant decreases compared to three control groups (P ≤ 0.01). The amounts of IgE in BAL fluids were not measurable in all groups. Conclusion: According to the results of this experiment we concluded that immunotherapy via the I.N co-administration of CpG/Ch.a in comparison with S.C route is more effective to stimulate the mucosal and regulatory responses in Ch.a induced asthma.
Three dimensional structure directs T-cell epitope dominance associated with allergy
Scott J Melton and Samuel J Landry Mon, 15 Sep 2008 00:00:00 -0000
Background: CD4+ T-cell epitope immunodominance is not adequately explained by peptide selectivity in class II major histocompatibility proteins, but it has been correlated with adjacent segments of conformational flexibility in several antigens. Methods: The published T-cell responses to two venom allergens and two aeroallergens were used to construct profiles of epitope dominance, which were correlated with the distribution of conformational flexibility, as measured by crystallographic B factors, solvent-accessible surface, COREX residue stability, and sequence entropy. Results: Epitopes associated with allergy tended to be excluded from and lie adjacent to flexible segments of the allergen. Conclusion: During the initiation of allergy, the N- and/or C-terminal ends of proteolytic processing intermediates were preferentially loaded into antigen presenting proteins for the priming of CD4+ T cells.
The Hoover's Sign of Pulmonary Disease: Molecular Basis and Clinical Relevance
Chambless R Johnston, Narayanaswamy Krishnaswamy and Guha Krishnaswamy Fri, 05 Sep 2008 00:00:00 -0000
In the 1920's, Hoover described a sign that could be considered a marker of severe airway obstruction. While readily recognizable at the bedside, it may easily be missed on a cursory physical examination. Hoover's sign refers to the inspiratory retraction of the lower intercostal spaces that occurs with obstructive airway disease. It results from alteration in dynamics of diaphragmatic contraction due to hyperinflation, resulting in traction on the rib margins by the flattened diaphragm. The sign is reported to have a sensitivity of 58% and specificity of 86% for detection of airway obstruction. Seen in up to 70% of patients with severe obstruction, this sign is associated with a patient's body mass index, severity of dyspnea and frequency of exacerbations. Hence the presence of the Hoover's sign may provide valuable prognostic information in patients with airway obstruction, and can serve to complement other clinical or functional tests. We present a clinical and molecular review of the Hoover's sign and explain how it could be utilized in the bedside and emergent management of airway disease.
The identification of allergen proteins in sugar beet (Beta vulgaris) pollen causing occupational allergy in greenhouses
Susanne Luoto, Wietske Lambert, Anna Blomqvist and Cecilia Emanuelsson Mon, 11 Aug 2008 00:00:00 -0000
Background: During production of sugar beet (Beta vulgaris) seeds in greenhouses, workers frequently develop allergic symptoms. The aim of this study was to identify and characterize possible allergens in sugar beet pollen. Methods: Sera from individuals at a local sugar beet seed producing company, having positive SPT and specific IgE to sugar beet pollen extract, were used for immunoblotting. Proteins in sugar beet pollen extracts were separated by 1- and 2-dimensional electrophoresis, and IgE-reactive proteins analyzed by liquid chromatography tandem mass spectrometry. Results: A 14 kDa protein was identified as an allergen, since IgE-binding was inhibited by the well-characterized allergen Che a 2, profilin, from the related species Chenopodium album. The presence of 17 kDa and 14 kDa protein homologues to both the allergens Che a 1 and Che a 2 were detected in an extract from sugar beet pollen, and partial amino acid sequences were determined, using inclusion lists for tandem mass spectrometry based on homologous sequences. Conclusion: Two occupational allergens were identified in sugar beet pollen showing sequence similarity with Chenopodium allergens. Sequence data were obtained by mass spectrometry (70 and 25%, respectively for Beta v 1 and Beta v 2), and can be used for cloning and recombinant expression of the allergens. As for treatment of Chenopodium pollinosis, immunotherapy with sugar beet pollen extracts may be feasible.
Polymorphisms in IL12A and cockroach allergy in children with asthma
Michael Pistiner, Gary M Hunninghake, Manuel E Soto-Quiros, Lydiana Avila, Amy Murphy, Jessica Lasky-Su, Brooke Schuemann, Barbara J Klanderman, Benjamin A Raby and Juan C Celedón Thu, 31 Jul 2008 00:00:00 -0000
Background: IL12A has been implicated in T-cell development and may thus influence the development of atopy and allergic diseases. Methods: We tested for association between four linkage disequilibrium (LD)-tagging SNPs (rs2243123, rs2243151, rs668998, and rs17826053) in IL12A and asthma and allergy-related (serum total and allergen-specific IgE, and skin test reactivity [STR] to two common allergens) phenotypes in two samples: 417 Costa Rican children with asthma and their parents, and 470 families of 503 white children in the Childhood Asthma Management Program (CAMP). The analysis was conducted using the family-based association test (FBAT) statistic implemented in the PBAT program. Results: Among Costa Rican children with asthma, homozygosity for the minor allele of each of two SNPs in IL12A (rs2243123 and rs2243151) was associated with increased risks of STR to American cockroach (P ≤ 0.03 for both SNPs), STR to German cockroach (P ≤ 0.01 for both SNPs), and having a positive IgE to German cockroach (P < 0.05 for both SNPs). Among children in CAMP, homozygosity for the minor allele of SNP rs2243151 in IL12A was inversely associated with STR to German cockroach (P = 0.03) and homozygosity for the minor allele of SNP rs17826053 in IL12A was associated with increased risks of STR to American cockroach (P = 0.01) and STR to German cockroach (P = 0.007). There was no significant association between any SNP in IL12A and asthma, STR to dust mite, or total IgE in Costa Rica or CAMP. Conclusion: Our findings suggest that variants in IL12A influence cockroach allergy among children with asthma.
X-linked agammaglobulinemia diagnosed late in life: case report and review of the literature
Justin R Sigmon, Ehab Kasasbeh and Guha Krishnaswamy Mon, 02 Jun 2008 00:00:00 -0000
Background: Common variable immune deficiency (CVID), one of the most common primary immunodeficiency diseases presents in adults, whereas X-linked agammaglobulinemia (XLA), an inherited humoral immunodeficiency, is usually diagnosed early in life after maternal Igs have waned. However, there have been several reports in the world literature in which individuals have either had a delay in onset of symptoms or have been misdiagnosed with CVID and then later found to have mutations in Bruton's tyrosine kinase (BTK) yielding a reclassification as adult-onset variants of XLA. The typical finding of absent B cells should suggest XLA rather than CVID and may be a sensitive test to detect this condition, leading to the more specific test (Btk mutational analysis). Further confirmation may be by mutational analyses. Methods: The records of 2 patients were reviewed and appropriate clinical data collected. BTK mutational analysis was carried out to investigate the suspicion of adult-presentation of XLA. A review of the world literature on delayed diagnosis of XLA and mild or "leaky" phenotype was performed. Results: 2 patients previously diagnosed with CVID associated with virtual absence of CD19+ B cells were reclassified as having a delayed diagnosis and adult-presentation of XLA. Patient 1, a 64 yr old male with recurrent sinobronchial infections had a low level of serum IgG of 360 mg/dl (normal 736–1900), IgA <27 mg/dl (normal 90–474), and IgM <25 mg/dl (normal 50–415). Patient 2, a 46 yr old male with recurrent sinopulmonary infections had low IgG of 260 mg/dl, low IgA <16 mg/dl, and normal IgM. Mutational analysis of BTK was carried out in both patients and confirmed the diagnosis of XLA Conclusion: These two cases represent an unusual adult-presentation of XLA, a humoral immunodeficiency usually diagnosed in childhood and the need to further investigate a suspicion of XLA in adult males with CVID particularly those associated with low to absent CD19+ B cells. A diagnosis of XLA can have significant implications including family counseling, detecting female carriers, and early intervention and treatment of affected male descendents.
Severe asthma and the omalizumab option
Christopher WT Miller, Narayanaswamy Krishnaswamy, Chambless Johnston and Guha Krishnaswamy Tue, 20 May 2008 00:00:00 -0000
Atopic diseases and asthma are increasing at a remarkable rate on a global scale. It is now well recognized that asthma is a chronic inflammatory disease of the airways. The inflammatory process in many patients is driven by an immunoglobulin E (IgE)-dependent process. Mast cell activation and release of mediators, in response to allergen and IgE, results in a cascade response, culminating in B lymphocyte, T lymphocyte, eosinophil, fibroblast, smooth muscle cell and endothelial activation. This complex cellular interaction, release of cytokines, chemokines and growth factors and inflammatory remodeling of the airways leads to chronic asthma. A subset of patients develops severe airway disease which can be extremely morbid and even fatal. While many treatments are available for asthma, it is still a chronic and incurable disease, characterized by exacerbation, hospitalizations and associated adverse effects of medications. Omalizumab is a new option for chronic asthma that acts by binding to and inhibiting the effects of IgE, thereby interfering with one aspect of the asthma cascade reviewed earlier. This is a humanized monoclonal antibody against IgE that has been shown to have many beneficial effects in asthma. Use of omalizumab may be influenced by the cost of the medication and some reported adverse effects including the rare possibility of anaphylaxis. When used in selected cases and carefully, omalizumab provides a very important tool in disease management. It has been shown to have additional effects in urticaria, angioedema, latex allergy and food allergy, but the data is limited and the indications far from clear. In addition to decreasing exacerbations, it has a steroid sparing role and hence may decrease adverse effects in some patients on high-dose glucocorticoids. Studies have shown improvement in quality of life measures in asthma following the administration of omalizumab, but the effects on pulmonary function are surprisingly small, suggesting a disconnect between pulmonary function, exacerbations and quality of life. Anaphylaxis may occur rarely with this agent and appropriate precautions have been recommended by the Food and Drug Administration (FDA). As currently practiced and as suggested by the new asthma guidelines, this biological agent is indicated in moderate or severe persistent allergic asthma (steps 5 and 6).
Current Opinion in Allergy and Clinical Immunology - Current Table Of Contents
Editorial introductions.
Page: viDOI: 10.1097/ACI.0b013e32831d8101
Applications of flow cytometry for the study of primary immune deficiencies.
Page: 499DOI: 10.1097/ACI.0b013e328312c790Authors: Oliveira, Joao B a; Notarangelo, Luigi D b; Fleisher, Thomas A a
Somatic mosaicism in primary immune deficiencies.
Page: 510DOI: 10.1097/ACI.0b013e328314b651Authors: Wada, Taizo a; Candotti, Fabio b
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Differential response of human basophil activation markers: a multi-parameter flow cytometry approach
Salvatore Chirumbolo, Antonio Vella, Riccardo Ortolani, Marzia De Gironcoli, Pietro Solero, Giuseppe Tridente and Paolo Bellavite Thu, 16 Oct 2008 00:00:00 -0000
Background: Basophils are circulating cells involved in hypersensitivity reactions and allergy but many aspects of their activation, including the sensitivity to external triggering factors and the molecular aspects of cell responses, are still to be focused. In this context, polychromatic flow cytometry (PFC) is a proper tool to investigate basophil function, as it allows to distinguish the expression of several membrane markers upon activation in multiple experimental conditions. Methods: Cell suspensions were prepared from leukocyte buffy coat of K2-EDTA anticoagulated blood specimens; about 1500-2500 cellular events for each tested sample, gated in the lymphocyte CD45dim area and then electronically purified as HLADRnon expressing/CD123bright, were identified as basophilic cells. Basophil activation with fMLP, anti-IgE and calcium ionophore A23187 was evaluated by studying up-regulation of the indicated membrane markers with a two-laser six-color PFC protocol. Results: Following stimulation, CD63, CD13, CD45 and the ectoenzyme CD203c up-regulated their membrane expression, while CD69 did not; CD63 expression occurred immediately (within 60 sec) but only in a minority of basophils, even at optimal agonist doses (in 33% and 14% of basophils, following fMLP and anti-IgE stimulation respectively). CD203c up-regulation occurred in the whole basophil population, even in CD63non expressing cells. Dose-dependence curves revealed CD203c as a more sensitive marker than CD63, in response to fMLP but not in response to anti-IgE and to calcium ionophore. Conclusion: Use of polychromatic flow cytometry allowed efficient basophil electronic purification and identification of different behaviors of the major activation markers. The simultaneous use of two markers of activation and careful choice of activator are essential steps for reliable assessment of human basophil functions.
Diversity of the gut microbiota and eczema in early life
Erick Forno, Andrew B Onderdonk, John McCracken, Augusto A Litonjua, Daniel Laskey, Mary L Delaney, Andrea M DuBois, Diane R Gold, Louise M Ryan, Scott T Weiss and Juan C Celedón Mon, 22 Sep 2008 00:00:00 -0000
Background: A modest number of prospective studies of the composition of the intestinal microbiota and eczema in early life have yielded conflicting results.ObjectiveTo examine the relationship between the bacterial diversity of the gut and the development of eczema in early life by methods other than stool culture. Methods: Fecal samples were collected from 21 infants at 1 and 4 months of life. Nine infants were diagnosed with eczema by the age of 6 months (cases) and 12 infants were not (controls). After conducting denaturating gradient gel electrophoresis (DGGE) of stool samples, we compared the microbial diversity of cases and controls using the number of electrophoretic bands and the Shannon index of diversity (H') as indicators. Results: Control subjects had significantly greater fecal microbial diversity than children with eczema at ages 1 (mean H' for controls = 0.75 vs. 0.53 for cases, P = 0.01) and 4 months (mean H' for controls = 0.92 vs. 0.59 for cases, P = 0.02). The increase in diversity from 1 to 4 months of age was significant in controls (P = 0.04) but not in children who developed eczema by 6 months of age (P = 0.32). Conclusion: Our findings suggest that reduced microbial diversity is associated with the development of eczema in early life.
CpG Immunotherapy in Chenopodium album sensitized mice: The comparison of IFN-gamma, IL-10 and IgE responses in intranasal and subcutaneous administrations
Tahereh Mousavi, Nader Tajik, Maziar Moradi and Masoomeh Fallah Radjabzadeh Wed, 17 Sep 2008 00:00:00 -0000
Background: Mucosal-based immunotherapy has been already used as an alternative form of allergen delivery. In asthma, the poor success rate of immune modulation could be a consequence of inadequate immune modulation in the airways. Previously, we have found that subcutaneous (S.C) co-administration of a homemade allergenic extract from Chenopodium album (Ch.a) pollen and Guanine-Cytosine containing deoxynucleotides (CpG-ODNs) is effective to prevent the inflammatory responses in mouse. In this study we used CpG/Ch.a for immunotherapy of Ch.a-induced asthma and compared the intranasal (I.N) and S.C routes of administration concerning IFN-γ, IL-10 and total IgE responses. Methods: Ch.a sensitized mice were treated intranasaly or subcutaneously using CpG and Ch.a. extract. IFN-γ, IL-10 and total IgE were measured in supernatant culture of splenocytes and bronchoalveolor lavage (BAL) fluids by ELISA. Student's t test was used in the analysis of the results obtained from the test and control mice. Results: We found that I.N administration of CpG/Ch.a in sensitized mice significantly increased the production of systemic and mucosal IFN-γ and IL-10 compared to phosphate buffered saline (PBS), Ch.a alone and control ODNs treated sensitized mice (P ≤ 0.001). On the other hand, S.C. route induced the systemic and mucosal IFN-γ in the lower levels than in I.N one, and failed to increase systemic IL-10 induction (P = 0.06). Total serum IgE in CpG/Ch.a treated mice in both routes showed significant decreases compared to three control groups (P ≤ 0.01). The amounts of IgE in BAL fluids were not measurable in all groups. Conclusion: According to the results of this experiment we concluded that immunotherapy via the I.N co-administration of CpG/Ch.a in comparison with S.C route is more effective to stimulate the mucosal and regulatory responses in Ch.a induced asthma.
Three dimensional structure directs T-cell epitope dominance associated with allergy
Scott J Melton and Samuel J Landry Mon, 15 Sep 2008 00:00:00 -0000
Background: CD4+ T-cell epitope immunodominance is not adequately explained by peptide selectivity in class II major histocompatibility proteins, but it has been correlated with adjacent segments of conformational flexibility in several antigens. Methods: The published T-cell responses to two venom allergens and two aeroallergens were used to construct profiles of epitope dominance, which were correlated with the distribution of conformational flexibility, as measured by crystallographic B factors, solvent-accessible surface, COREX residue stability, and sequence entropy. Results: Epitopes associated with allergy tended to be excluded from and lie adjacent to flexible segments of the allergen. Conclusion: During the initiation of allergy, the N- and/or C-terminal ends of proteolytic processing intermediates were preferentially loaded into antigen presenting proteins for the priming of CD4+ T cells.
The Hoover's Sign of Pulmonary Disease: Molecular Basis and Clinical Relevance
Chambless R Johnston, Narayanaswamy Krishnaswamy and Guha Krishnaswamy Fri, 05 Sep 2008 00:00:00 -0000
In the 1920's, Hoover described a sign that could be considered a marker of severe airway obstruction. While readily recognizable at the bedside, it may easily be missed on a cursory physical examination. Hoover's sign refers to the inspiratory retraction of the lower intercostal spaces that occurs with obstructive airway disease. It results from alteration in dynamics of diaphragmatic contraction due to hyperinflation, resulting in traction on the rib margins by the flattened diaphragm. The sign is reported to have a sensitivity of 58% and specificity of 86% for detection of airway obstruction. Seen in up to 70% of patients with severe obstruction, this sign is associated with a patient's body mass index, severity of dyspnea and frequency of exacerbations. Hence the presence of the Hoover's sign may provide valuable prognostic information in patients with airway obstruction, and can serve to complement other clinical or functional tests. We present a clinical and molecular review of the Hoover's sign and explain how it could be utilized in the bedside and emergent management of airway disease.
The identification of allergen proteins in sugar beet (Beta vulgaris) pollen causing occupational allergy in greenhouses
Susanne Luoto, Wietske Lambert, Anna Blomqvist and Cecilia Emanuelsson Mon, 11 Aug 2008 00:00:00 -0000
Background: During production of sugar beet (Beta vulgaris) seeds in greenhouses, workers frequently develop allergic symptoms. The aim of this study was to identify and characterize possible allergens in sugar beet pollen. Methods: Sera from individuals at a local sugar beet seed producing company, having positive SPT and specific IgE to sugar beet pollen extract, were used for immunoblotting. Proteins in sugar beet pollen extracts were separated by 1- and 2-dimensional electrophoresis, and IgE-reactive proteins analyzed by liquid chromatography tandem mass spectrometry. Results: A 14 kDa protein was identified as an allergen, since IgE-binding was inhibited by the well-characterized allergen Che a 2, profilin, from the related species Chenopodium album. The presence of 17 kDa and 14 kDa protein homologues to both the allergens Che a 1 and Che a 2 were detected in an extract from sugar beet pollen, and partial amino acid sequences were determined, using inclusion lists for tandem mass spectrometry based on homologous sequences. Conclusion: Two occupational allergens were identified in sugar beet pollen showing sequence similarity with Chenopodium allergens. Sequence data were obtained by mass spectrometry (70 and 25%, respectively for Beta v 1 and Beta v 2), and can be used for cloning and recombinant expression of the allergens. As for treatment of Chenopodium pollinosis, immunotherapy with sugar beet pollen extracts may be feasible.
Polymorphisms in IL12A and cockroach allergy in children with asthma
Michael Pistiner, Gary M Hunninghake, Manuel E Soto-Quiros, Lydiana Avila, Amy Murphy, Jessica Lasky-Su, Brooke Schuemann, Barbara J Klanderman, Benjamin A Raby and Juan C Celedón Thu, 31 Jul 2008 00:00:00 -0000
Background: IL12A has been implicated in T-cell development and may thus influence the development of atopy and allergic diseases. Methods: We tested for association between four linkage disequilibrium (LD)-tagging SNPs (rs2243123, rs2243151, rs668998, and rs17826053) in IL12A and asthma and allergy-related (serum total and allergen-specific IgE, and skin test reactivity [STR] to two common allergens) phenotypes in two samples: 417 Costa Rican children with asthma and their parents, and 470 families of 503 white children in the Childhood Asthma Management Program (CAMP). The analysis was conducted using the family-based association test (FBAT) statistic implemented in the PBAT program. Results: Among Costa Rican children with asthma, homozygosity for the minor allele of each of two SNPs in IL12A (rs2243123 and rs2243151) was associated with increased risks of STR to American cockroach (P ≤ 0.03 for both SNPs), STR to German cockroach (P ≤ 0.01 for both SNPs), and having a positive IgE to German cockroach (P < 0.05 for both SNPs). Among children in CAMP, homozygosity for the minor allele of SNP rs2243151 in IL12A was inversely associated with STR to German cockroach (P = 0.03) and homozygosity for the minor allele of SNP rs17826053 in IL12A was associated with increased risks of STR to American cockroach (P = 0.01) and STR to German cockroach (P = 0.007). There was no significant association between any SNP in IL12A and asthma, STR to dust mite, or total IgE in Costa Rica or CAMP. Conclusion: Our findings suggest that variants in IL12A influence cockroach allergy among children with asthma.
X-linked agammaglobulinemia diagnosed late in life: case report and review of the literature
Justin R Sigmon, Ehab Kasasbeh and Guha Krishnaswamy Mon, 02 Jun 2008 00:00:00 -0000
Background: Common variable immune deficiency (CVID), one of the most common primary immunodeficiency diseases presents in adults, whereas X-linked agammaglobulinemia (XLA), an inherited humoral immunodeficiency, is usually diagnosed early in life after maternal Igs have waned. However, there have been several reports in the world literature in which individuals have either had a delay in onset of symptoms or have been misdiagnosed with CVID and then later found to have mutations in Bruton's tyrosine kinase (BTK) yielding a reclassification as adult-onset variants of XLA. The typical finding of absent B cells should suggest XLA rather than CVID and may be a sensitive test to detect this condition, leading to the more specific test (Btk mutational analysis). Further confirmation may be by mutational analyses. Methods: The records of 2 patients were reviewed and appropriate clinical data collected. BTK mutational analysis was carried out to investigate the suspicion of adult-presentation of XLA. A review of the world literature on delayed diagnosis of XLA and mild or "leaky" phenotype was performed. Results: 2 patients previously diagnosed with CVID associated with virtual absence of CD19+ B cells were reclassified as having a delayed diagnosis and adult-presentation of XLA. Patient 1, a 64 yr old male with recurrent sinobronchial infections had a low level of serum IgG of 360 mg/dl (normal 736–1900), IgA <27 mg/dl (normal 90–474), and IgM <25 mg/dl (normal 50–415). Patient 2, a 46 yr old male with recurrent sinopulmonary infections had low IgG of 260 mg/dl, low IgA <16 mg/dl, and normal IgM. Mutational analysis of BTK was carried out in both patients and confirmed the diagnosis of XLA Conclusion: These two cases represent an unusual adult-presentation of XLA, a humoral immunodeficiency usually diagnosed in childhood and the need to further investigate a suspicion of XLA in adult males with CVID particularly those associated with low to absent CD19+ B cells. A diagnosis of XLA can have significant implications including family counseling, detecting female carriers, and early intervention and treatment of affected male descendents.
Severe asthma and the omalizumab option
Christopher WT Miller, Narayanaswamy Krishnaswamy, Chambless Johnston and Guha Krishnaswamy Tue, 20 May 2008 00:00:00 -0000
Atopic diseases and asthma are increasing at a remarkable rate on a global scale. It is now well recognized that asthma is a chronic inflammatory disease of the airways. The inflammatory process in many patients is driven by an immunoglobulin E (IgE)-dependent process. Mast cell activation and release of mediators, in response to allergen and IgE, results in a cascade response, culminating in B lymphocyte, T lymphocyte, eosinophil, fibroblast, smooth muscle cell and endothelial activation. This complex cellular interaction, release of cytokines, chemokines and growth factors and inflammatory remodeling of the airways leads to chronic asthma. A subset of patients develops severe airway disease which can be extremely morbid and even fatal. While many treatments are available for asthma, it is still a chronic and incurable disease, characterized by exacerbation, hospitalizations and associated adverse effects of medications. Omalizumab is a new option for chronic asthma that acts by binding to and inhibiting the effects of IgE, thereby interfering with one aspect of the asthma cascade reviewed earlier. This is a humanized monoclonal antibody against IgE that has been shown to have many beneficial effects in asthma. Use of omalizumab may be influenced by the cost of the medication and some reported adverse effects including the rare possibility of anaphylaxis. When used in selected cases and carefully, omalizumab provides a very important tool in disease management. It has been shown to have additional effects in urticaria, angioedema, latex allergy and food allergy, but the data is limited and the indications far from clear. In addition to decreasing exacerbations, it has a steroid sparing role and hence may decrease adverse effects in some patients on high-dose glucocorticoids. Studies have shown improvement in quality of life measures in asthma following the administration of omalizumab, but the effects on pulmonary function are surprisingly small, suggesting a disconnect between pulmonary function, exacerbations and quality of life. Anaphylaxis may occur rarely with this agent and appropriate precautions have been recommended by the Food and Drug Administration (FDA). As currently practiced and as suggested by the new asthma guidelines, this biological agent is indicated in moderate or severe persistent allergic asthma (steps 5 and 6).
Current Opinion in Allergy and Clinical Immunology - Current Table Of Contents
Editorial introductions.
Page: viDOI: 10.1097/ACI.0b013e32831d8101
Applications of flow cytometry for the study of primary immune deficiencies.
Page: 499DOI: 10.1097/ACI.0b013e328312c790Authors: Oliveira, Joao B a; Notarangelo, Luigi D b; Fleisher, Thomas A a
Somatic mosaicism in primary immune deficiencies.
Page: 510DOI: 10.1097/ACI.0b013e328314b651Authors: Wada, Taizo a; Candotti, Fabio b
Sites:
Allergen Response Research Center: Conducts Phase II - Phase IV clinical studies. Designed to provide an atmosphere with uniform concentrations of naturally occurring allergens for periods up to 12 hours. Georgia based.Allergome - A Database of Allergenic Molecules: Allergome.org. Archive molecules
Asthma and Allergy Information and Research: AAIR: Information for patients and parents of patients on a wide range of allergy and asthma topics. Few graphics (so loads fast) but lots of text. Answers to questions people ask.
Asthma Clinical Research Network: ACRN: The Asthma Clinical Research Network (ACRN) is a multi-center group designed to conduct multiple studies of asthma. The ACRN is dedicated to conducting well designed clinical trials for evaluation of new and existing therapeutic approaches for asthma and for dissemination of laboratory and clinic...
UCB Institute of Allergy: Allergy, institute of allergy, control your allergy with UCB. Allergy studies and advice to prevent an allergy, know more about your allergy. The UCB researches allergy and publishes information on allergy.
This directory is based on the Open Directory and may have been modified