Allergy & Immunology Medical and Health News Headlines

Inhalation of Staphylococcus aureus enterotoxin A induces IFN-gamma and CD8 T cell-dependent airway and interstitial lung pathology in mice.

J Immunol. 2008 Sep 1;181(5):3698-705

Authors: Muralimohan G, Rossi RJ, Guernsey LA, Thrall RS, Vella AT

Staphylococcus aureus, a primary source of bacterial superantigen (SAg), is known to colonize the human respiratory tract and has been implicated in airway inflammation. Studies have documented a role for SAgs in respiratory disorders, such as nasal polyps, chronic obstructive pulmonary disease, chronic rhinosinusitis, and asthma. However, cellular and molecular mediators involved in SAg-mediated pulmonary disease have not been clearly identified. In this study, we investigated the effect of intranasal staphylococcal enterotoxin A (SEA) exposure on murine lung. The pathological features in the lung resulting from SEA exposure had characteristics of both obstructive and restrictive pulmonary disorders. There was also an increase in bronchoalveolar lavage protein concentration and cellularity following SEA challenge. Massive CD8(+)Vbeta3(+) T cell accumulation observed in the lung was dependent on CD4 T cell help, both for recruitment and for IFN-gamma synthesis. The primary source of IFN-gamma synthesis was CD8 T cells, and depletion of these cells abrogated disease. IFN-gamma deficiency also prevented SEA-mediated disease, and this was by enhancing early recruitment of neutrophils as detected in the bronchoalveolar lavage. Thus, IFN-gamma appeared to selectively aid the recruitment of T cells to the lungs while preventing the neutrophil accumulation. Therefore, our results show that IFN-gamma-producing CD8 T cells mediated pulmonary alveolitis and inflammation, which were dependent upon CD4 T cells for their recruitment to the lung.

PMID: 18714046 [PubMed - in process]

Coexistence of asthma and allergic rhinitis in adult patients attending allergy clinics: ONEAIR study.

J Investig Allergol Clin Immunol. 2008;18(4):233-8

Authors: Navarro A, Valero A, Juliá B, Quirce S

BACKGROUND: Several studies have shown links between the upper and lower airways in allergic patients. OBJECTIVES: This study aimed to evaluate the prevalence of rhinitis in patients with allergic asthma attending allergy outpatient clinics and to examine the interrelationship between both conditions. METHODS: An epidemiological prospective study was carried out during the period 2004-2005 and 170 allergists from all over the country participated. After obtaining written informed consent, we collected clinical and demographic data, a personal and family history of allergic diseases, and data on the duration and severity of asthma and rhinitis. These data were classified according to the criteria of the Global Initiative for Asthma and the Allergic Rhinitis and its Impact on Asthma guidelines, respectively. RESULTS: A total of 968 subjects were screened and 942 were enrolled in the study. Mean (SD) age was 35.5 (14) years and 63% were female. Of these patients, 89.5% presented with allergic rhinitis. The duration of the disease was 12.6 (8.9) years for rhinitis and 11.4 (9.6) years for asthma (P < .0001). The severity of asthma was classified as intermittent (39%), mild persistent (30%), moderate persistent (27%), and severe persistent (4%). Rhinitis was classified as mild intermittent (24%), moderate/severe intermittent (22%), mild persistent (19%) and moderate/severe persistent (35%). A significant correlation was found (P < .0001) between the severity of rhinitis and asthma. The prevalence of allergic rhinitis was inversely correlated with the age of the patients (P < .0001) and the severity of asthma (P < .05). CONCLUSION: This study reinforces the high prevalence of allergic rhinitis in patients with asthma, which can affect as many as 89.5%.

PMID: 18714529 [PubMed - in process]

(CCTTT)n polymorphism of NOS2A in nasal polyposis and asthma: a case-control study.

J Investig Allergol Clin Immunol. 2008;18(4):239-44

Authors: Pascual M, Sanz C, Isidoro-García M, Dávila I, Moreno E, Laffond E, Lorente F

BACKGROUND: Nitric Oxide (NO) has been proposed as an important signaling molecule. NO produced by the inducible NO synthase enzyme NOS2A is generated at high levels in certain types of inflammation. A pentanucleotide polypyrimidine microsatellite CCTTT has been identified in the promoter region of the NOS2A gene. OBJECTIVE: The aim of this study was to analyze the (CCTTT)n polymorphism in patients with asthma and nasal polyposis. MATERIAL AND METHODS: The study included 292 white individuals (194 patients and 98 controls). Asthma was diagnosed according to American Thoracic Society criteria and classified in accordance with the guidelines of the Global Initiative for Asthma. Skin prick tests were performed in all individuals. The polymorphism was analyzed by an electrophoretic method and by direct sequencing. RESULTS: A significant association was detected for a 15-repeat cutoff in nasal polyposis (Fisher P value = .0001, Monte Carlo P value [after 10(4) simulations] = .002). Multivariate analysis adjusted for age and sex confirmed this association with an increased risk of nasal polyposis (odds ratio, 14.39; 95% confidence interval, 3.02-68.60; P = .001). CONCLUSION: The number of CCTTT repeats in the promoter region of NOS2A could be associated with the inflammatory process of nasal polyposis in our population. Modifications of NOS2A transcription levels could be involved in this association.

PMID: 18714530 [PubMed - in process]

Emedastine difumarate inhibits histamine-induced collagen synthesis in dermal fibroblasts.

J Investig Allergol Clin Immunol. 2008;18(4):245-52

Authors: Murota H, Bae S, Hamasaki Y, Maruyama R, Katayama I

BACKGROUND: Mast cell-derived histamine is known to act on dermal fibroblasts and contribute to formation of an intractable chronic allergic dermatitis. Although this fibrotic event may also occur in other organs such as the nasal mucosa, no direct evidence has been reported as to whether responsiveness to histamine by fibroblasts derived from different organs is of the same intensity. Furthermore, while type 1 histamine receptor (H1R) blockers have been shown to be effective for alleviation of the symptoms of allergic diseases, their ability to affect histamine-induced tissue remodeling has not yet been clarified. OBJECTIVE: Our aim was to study the effect of H1R-blockers on histamine-induced tissue remodeling. METHODS: A macroarray assay was used for a comprehensive analysis of histamine-induced gene expression by normal human fibroblasts. Fibroblasts derived from skin or nasal mucosa were cultured in the presence of various concentrations of histamine, and the synthesis of type 1 collagen was measured by means of semi-quantitative reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay. To determine the effect of H1R blockers, diphenhydramine hydrochloride and emedastine difumarate were investigated in this assay. RESULTS: Histamine induced expression of various kinds of fibrogenic molecules in fibroblasts. Increased type 1 collagen expression was observed in fibroblasts treated with high-dose (0.1 mM to 1 microM) and low-dose (1 pM) histamine. This histamine-induced type 1 collagen synthesis was effectively diminished by emedastine difumarate. While organ specificity seems to be involved, emedastine difumarate is considered to be an effective drug for reversal of such histamine-induced remodeling in the skin. CONCLUSIONS: We found that the expression of fibroblast-derived genes is differentially regulated by different concentrations of histamine and that the robustness of the inhibitory action of H1R blockers is different for skin-derived and nasal mucosa-derived fibroblasts. We believe that our findings may contribute to a better understanding of the mechanisms of histamine-induced tissue remodeling and provide information useful for the management of refractory allergic dermatitis.

PMID: 18714531 [PubMed - in process]

Clinical and immunologic features of pediatric patients with common variable immunodeficiency and respiratory complications.

J Investig Allergol Clin Immunol. 2008;18(4):260-5

Authors: Aydogan M, Eifan AO, Gocmen I, Ozdemir C, Bahceciler NN, Barlan IB

BACKGROUND: Common variable immunodeficiency (CVID) is the term used to describe a heterogeneous group of B-cell deficiency syndromes characterized by hypogammaglobulinemia, impaired antibody production, and recurrent bacterial infections. OBJECTIVES: To determine the clinical manifestations and perform an immunological analysis of pediatric CVID patients suffering from respiratory complications. METHODS: The records of 10 patients with CVID who were followed up from 1992 to 2005 (6 males and 4 females) with a median (interquartile range) age of 13.9 (10.4-19.4) years were reviewed. All patients met the standard criteria set for CVID. RESULTS: Median total serum levels of immunoglobulin (Ig) G, IgM, and IgA in mg/dL were 383.5 (239.2-574.5), 32.5 (17.0-117.0), and 12.5 (5.0-30.7), respectively. Median age at the onset of symptoms, at CVID diagnosis, and on starting intravenous Ig therapy was 4.0 (0.8-6.2), 9.4 (6.7-11.3), and 9.1 (7.0-11.6) years, respectively. Associated disorders were recurrent infections (100%), bronchiectasis (90%), and growth failure (80%), whereas malabsorption, malignant neoplasm, inflammatory bowel disease, and autoimmune disorders were less common. All bronchiectatic patients had a low percentage of B cells, with an average of 4% (range, 1%-7%). The characteristic computed tomography finding in patients with CVID was a multilobar pattern. Malignant neoplasm developed an average of 11.5 (range, 6.5-20.2) years after the diagnosis of CVID was made. CONCLUSION: Recurrent respiratory infection should be evaluated to rule out CVID. Early diagnosis and intravenous Ig replacement therapy may reduce the frequency of respiratory infection. Low levels of serum Ig and percentage of B lymphocytes at diagnosis are important parameters for identifying patients at risk of structural lung damage.

PMID: 18714533 [PubMed - in process]

Alterations in humoral immunity in relatives of patients with common variable immunodeficiency.

J Investig Allergol Clin Immunol. 2008;18(4):266-71

Authors: Aghamohammadi A, Sedighipour L, Saeed SE, Kouhkan A, Heydarzadeh M, Pourpak Z

BACKGROUND AND OBJECTIVES: It has been reported that there is a high prevalence of immunodeficiency and autoimmunity in relatives of patients with common variable immunodeficiency (CVID). The aim of this study was to determine the prevalence of immunoglobulin deficiency in relatives of patients with CVID in Iran, where there is a high rate of consanguineous marriage. METHODS: A descriptive study was undertaken in 64 family members of 23 unrelated CVID patients. The group contained 17 fathers, 18 mothers, 18 sisters, 9 brothers, and 2 children. Serum immunoglobulin levels were measured by nephelometry. Immunoglobulin (Ig) G subclass levels were measured in a subgroup of 36 individuals. Serum IgA levels were confirmed by enzyme-linked immunosorbent assay for subjects with suspected IgA deficiency. RESULTS: The rate of consanguineous marriage in families containing relatives with antibody deficiencies was significantly higher than in those families in whom relatives did not have immune deficiencies. IgA deficiency was observed in 2 relatives of patients with CVID. Also CVID was observed in 2 family members. In 3 fathers and 1 brother, IgM levels were lower than normal. Three relatives had IgG4 deficiency and 1 person had combined IgG4 and IgG2 deficiency. Twenty percent of the relatives had hypogammaglobulinemia (including IgA deficiency, CVID, decreased levels of IgM, and IgG subclass deficiencies). CONCLUSION: In our study, alteration in humoral immunity in relatives of CVID patients was higher than previously reported, and this could be attributed to the high rate of consanguineous marriage in Iran. Since the family members of CVID patients are at high risk of hypogammaglobulinemia, it is advisable that they be evaluated for immunodeficiency disorders and monitored throughout their lifetimes.

PMID: 18714534 [PubMed - in process]

Soluble CD40 ligand and soluble P-selectin in allergic asthma patients during exercise-induced bronchoconstriction.

J Investig Allergol Clin Immunol. 2008;18(4):272-8

Authors: Zietkowski Z, Skiepko R, Tomasiak MM, Bodzenta-Lukaszyk A

BACKGROUND: The interactions between CD40 and its ligand, CD40L, control humoral and cell-mediated immune responses. CD40 ligation may promote asthma-associated inflammatory responses in the airways. Many reports confirm the inflammatory basis of exercise-induced bronchoconstriction (EIB) in asthmatics. METHODS: The study was conducted in a group of 19 asthmatic patients (11 with EIB, 8 without EIB) and 8 healthy volunteers. We analyzed the changes in plasma concentrations of soluble CD40 ligand (sCD40L) and soluble P-selectin (sP-selectin) induced by intensive exercise. We also studied possible correlations with the results of measurements commonly associated with asthmatic inflammation. RESULTS: The study revealed statistically significant higher baseline concentrations of sCD40L--but not sP-selectin--in the group of asthmatics with EIB than in those without. In the asthmatic patients with EIB, sCD40L and sP-selectin concentrations increased significantly 30 minutes after exercise and returned to baseline 24 hours after exercise. Baseline concentrations of sCD40L correlated with baseline sP-selectin or fractional exhaled nitric oxide concentration (FE(NO)), an increase in sP-selectin 30 minutes after exercise, and changes in FE(NO) or bronchial hyperresponsiveness 24 hours after exercise. A statistically significant correlation between an increase in sCD40L concentrations 30 minutes after exercise and an increase in FE(NO) 24 hours after exercise or baseline eosinophil cationic protein was observed. CONCLUSION: After exercise in the group of allergic asthmatics with EIB, upregulation of CD40L by increased expression of inflammatory molecules and improved sensitivity of CD40-responsive cell types to the effects of proinflammatory cytokines may play an important role in the increased airway inflammation observed after postexercise bronchoconstriction.

PMID: 18714535 [PubMed - in process]

CD30 serum levels and response to hymenoptera venom immunotherapy.

J Investig Allergol Clin Immunol. 2008;18(4):279-83

Authors: Foschi FG, Emiliani F, Savini S, Quercia O, Stefanini GF

BACKGROUND: The glycoprotein CD30 is expressed and released by T lymphocytes that secrete type 2 helper cytokines of (T(H)2). These molecules play a role in the pathogenesis of allergic diseases. Venom immunotherapy has proven to be very effective in hymenoptera venom allergy through a shift in cytokine production from T(H)2-type cytokines to T(H)1-type cytokines. OBJECTIVE: To evaluate the relationship between the soluble form of CD30 (sCD30) and venom immunotherapy in patients with hymenoptera venom allergy. MATERIALS AND METHODS: sCD30 levels were assayed by enzyme-linked immunosorbent assay in the sera of 61 healthy controls and 14 patients with hymenoptera venom allergy who had undergone immunotherapy before treatment and 1,3, and 12 months after treatment started. Nine patients were allergic to Apis venom, 4 to Vespula venom, and 1 to Polistes venom. RESULTS: CD30 serum levels (median, interquartile range) were significantly higher in venom-allergic patients before treatment (33.6 U/mL; 14.8-61.6) than in controls (9.7 U/mL, 1.9-21.3) (P < .000). These levels decreased progressively during treatment in all patients except 2 (P < .000). At the third month of therapy, the levels reached statistical significance in comparison with baseline. CONCLUSIONS: This study shows that sCD30 levels are significantly higher in patients with hymenoptera venom allergy and indirectly confirms a preferential T(H)2-type cytokine production in these patients. sCD30 expression decreases during immunotherapy, thus confirming the immunomodulatory role of this treatment in promoting a shift to T(H)1-type cytokines.

PMID: 18714536 [PubMed - in process]

Activation of basophils by stem cell factor: comparison with insulin-like growth factor-I.

J Investig Allergol Clin Immunol. 2008;18(4):293-9

Authors: Koketsu R, Suzukawa M, Kawakami A, Komiya A, Ra C, Yamamoto K, Yamaguchi M

BACKGROUND: Basophils are an active participant in the pathogenesis of local inflammation in allergic diseases such as asthma, but it is not fully known how basophil activation is regulated in inflamed tissue. OBJECTIVE: In order to clarify the control mechanisms of basophil activation in chronic inflammation and at remodeling sites, we analyzed the effects of fibroblast-derived cytokines, stem cell factor (SCF), and insulin-like growth factor-I (IGF-I) on basophils. METHODS: The effects of SCF and IGF-I on degranulation and surface activation marker expression by basophils were assessed and compared. RESULTS: SCF enhanced human basophil histamine release elicited by some, but not all, secretagogues; degranulation in response to IgE- or FcepsilonRI-mediated stimulation and 12-o-tetradecanoyl-phorbol-13-acetate (TPA) was enhanced by SCF. SCF slightly enhanced ionophore A23187-induced histamine release by basophils from some donors, but it failed to affect the release elicited by monocyte chemoattractant protein-1 (MCP-1), formylmethionyl-leucyl-phenylalanine (FMLP) or C5a. The repertoire of secretagogues responsive to SCF was similar to that of IGF-I. Expression levels of both CD11b and CD69 markers were significantly enhanced by the combination of SCF and IGF-I. CONCLUSIONS: These results suggest that SCF and IGF-I may modify the activation of basophils in a similar and/or synergistic fashion. Interaction of basophils with these cytokines might be involved in the pathogenesis of local inflammation and the remodeling process in asthma.

PMID: 18714538 [PubMed - in process]

Asthma and allergic rhinitis in a patient with BTK deficiency.

J Investig Allergol Clin Immunol. 2008;18(4):300-4

Authors: Shabestari MS, Rezaei N

BTK deficiency is a primary immunodeficiency disease characterized by the absence of circulating B cells and agammaglobulinemia. While recurrent bacterial infections are the most common manifestations, symptoms of allergy and asthma are rare. We present the case of a 7-year-old boy who presented with asthma symptoms, allergic rhinitis, and severe papular urticaria. He had a positive skin prick test to aeroallergens and food allergens. However, further laboratory tests revealed a low number of B cells and decreased serum levels of all immunoglobulin isotypes. Molecular analysis revealed a mutation in the BTK gene. Although patients with BTK deficiency seem to be protected from atopy, our patient had allergic symptoms suggesting a bias toward a type 2 helper T cell pattern in this case. Primary antibody deficiency should be considered in the differential diagnosis of pediatric allergy and asthma when respiratory infection persists despite appropriate treatment.

PMID: 18714539 [PubMed - in process]

Anaphylaxis to oral iron salts. desensitization protocol for tolerance induction.

J Investig Allergol Clin Immunol. 2008;18(4):305-8

Authors: de Barrio M, Fuentes V, Tornero P, Sánchez I, Zubeldia J, Herrero T

Allergies to iron salts are seldom reported. We studied a patient with iron-deficiency anemia who had suffered anaphylactic reactions caused by oral iron salts. An allergy study was performed using single-blind, placebo-controlled oral challenge and skin tests with various iron salts as well as excipients in commercial formulations. Oral challenges were positive for 2 of the commercial formulations of iron salts. Intradermal tests with ferrous sulphate and ferrous lactate also showed positive results. All of the cutaneous tests using the excipients were negative. A desensitization protocol was designed which enabled us to readminister ferrous sulphate, although antihistamines were necessary to guarantee good tolerance to iron salts. We report a patient with allergy to iron salts, positive skin tests, and positive controlled challenge. We highlight the desensitization protocol designed to complete the therapeutic management of the anemia.

PMID: 18714540 [PubMed - in process]

Desensitization to co-trimoxazole in a patient with fixed drug eruption.

J Investig Allergol Clin Immunol. 2008;18(4):309-11

Authors: Patriarca G, Schiavino D, Buonomo A, Aruanno A, Altomonte G, Nucera E

Although co-trimoxazole is a major cause of fixed drug eruption, there are no reports in the literature of desensitization protocols for co-trimoxazole in such patients. We present the case of an 85-year-old woman with a fixed drug eruption to co-trimoxazole. Since she needed co-trimoxazole therapy for treatment of infection of a prosthetic hip by Staphylococcus aureus, she underwent allergy testing with co-trimoxazole and its components sulfamethoxazole and trimethoprim. Allergy tests were all negative and a diagnosis of nonallergic hypersensitivity reaction to co-trimoxazole was made. Based on previous experience, we decided to attempt a desensitization protocol with co-trimoxazole. After 10 days, the patient could receive 800 mg of sulfamethoxazole and 160 mg of trimethoprim twice a day and no adverse reactions were observed. We suggest that desensitization protocols with co-trimoxazole be considered in patients with fixed drug eruption, especially when there are no alternative drugs.

PMID: 18714541 [PubMed - in process]

Diurnal variation of nasal nitric oxide levels in healthy subjects.

J Investig Allergol Clin Immunol. 2008;18(4):316-7

Authors: Dressel H, Bihler A, Jund F, de la Motte D, Nowak D, Jörres RA, Kramer MF

PMID: 18714543 [PubMed - in process]

Late patch test reaction to dichlorophene.

J Investig Allergol Clin Immunol. 2008;18(4):317-8

Authors: Barbuzza O, Guarneri F, Galtieri G, Vaccaro M

PMID: 18714544 [PubMed - in process]

Tolerability of lumiracoxib in patients with analgesic intolerance.

J Investig Allergol Clin Immunol. 2008;18(4):318-9

Authors: Celikel S, Isik SR, Karakaya G, Kalyoncu AF

PMID: 18714545 [PubMed - in process]

Allergen-specific IgE to inhalant and food allergens and total IgE values in China: comparison of 2 commercial immunoassays.

J Investig Allergol Clin Immunol. 2008;18(4):319-21

Authors: Sun BQ, Mahler M, Jiang M, Li J, Zhong NS

PMID: 18714546 [PubMed - in process]