Assessing IgE sensitization profiles to birch and timothy grass pollen allergens in birch pollen allergic blood donors using an oligoplex specific IgE assay.

IgE sensitization profiles to single birch allergens in birch-sensitized patients differ among European countries. The aim of this study was to determine the distribution of specific IgE antibodies to major and minor birch pollen allergens in a population of allergic Norwegian individuals by using a birch allergic blood donor population as a surrogate sample. Sixty blood donors were recruited and sampled based on birch allergy symptoms such as rhinitis, rhinoconjunctivitis and/or mild asthma in previous seasons. All sera were collected before start of the pollen season and tested using a line blot assay (Euroimmun AG, Lübeck, Germany) for IgE to birch and timothy pollen. Both extracts, single allergens, and cross-reacting carbohydrate determinants (CCD) were analysed. Only donors with specific IgE to birch and/or timothy grass were further evaluated. Specific IgE to birch pollen extract was found in 52 sera, and sensitization to timothy grass in 40 sera. Specific IgE to Bet v 1 was predominant in contrast to Bet v 4 which was absent. However, sensitization to the minor allergens Bet v 2 and 6 was always found together with high levels of IgE to Bet v 1. Subjects sensitized to the profilin Bet v 2 from birch were also sensitized to Phl p 12 from timothy grass. In conclusion, there was predominantly Bet v 1 sensitization in this cohort and low sensitization to minor allergens and cross-reactive allergens (Bet v 2, Bet v 4, Phl p 7 and Phl p 12).

Antitumor, Anti-Inflammatory and Antiallergic Effects of Agaricus blazei Mushroom Extract and the Related Medicinal Basidiomycetes Mushrooms, Hericium erinaceus and Grifola frondosa: A Review of Preclinical and Clinical Studies.

Since the 1980s, medicinal effects have been documented in scientific studies with the related Basidiomycota mushrooms Agaricus blazei Murill (AbM), Hericium erinaceus (HE) and Grifola frondosa (GF) from Brazilian and Eastern traditional medicine. Special focus has been on their antitumor effects, but the mushrooms' anti-inflammatory and antiallergic properties have also been investigated. The antitumor mechanisms were either direct tumor attack, e.g., apoptosis and metastatic suppression, or indirect defense, e.g., inhibited tumor neovascularization and T helper cell (Th) 1 immune response. The anti-inflammatory mechanisms were a reduction in proinflammatory cytokines, oxidative stress and changed gut microbiota, and the antiallergic mechanism was amelioration of a skewed Th1/Th2 balance. Since a predominant Th2 milieu is also found in cancer, which quite often is caused by a local chronic inflammation, the three conditions-tumor, inflammation and allergy-seem to be linked. Further mechanisms for HE were increased nerve and beneficial gut microbiota growth, and oxidative stress regulation. The medicinal mushrooms AbM, HE and GF appear to be safe, and can, in fact, increase longevity in animal models, possibly due to reduced tumorigenesis and oxidation. This article reviews preclinical and clinical findings with these mushrooms and the mechanisms behind them.

A novel HLA-DQA1 allele, DQA1*01:05:03, identified in a patient with suspected celiac disease.

A novel HLA-DQA1 allele, officially named DQA1*01:05:03 by the WHO Nomenclature Committee, was identified in a Norwegian patient with suspected celiac disease. The allele was sequenced by next-generation sequencing and is identical to DQA1*01:05:01:01 with the exception of one synonymous nucleotide substitution in exon two.

Agaricus blazei-Based Mushroom Extract Supplementation to Birch Allergic Blood Donors: A Randomized Clinical Trial.

Since Agaricus blazei Murill (AbM) extract reduced specific IgE and ameliorated a skewed Th1/Th2 balance in a mouse allergy model, it was tested in blood donors with self-reported, IgE-positive, birch pollen allergy and/or asthma. Sixty recruited donors were randomized in a placebo-controlled, double-blinded study with pre-seasonal, 7-week, oral supplementation with the AbM-based extract AndosanTM. Before and after the pollen season, questionnaires were answered for allergic rhino-conjunctivitis, asthma, and medication; serum IgE was measured, and Bet v 1-induced basophil activation was determined by CD63 expression. The reported general allergy and asthma symptoms and medication were significantly reduced in the AbM compared to the placebo group during pollen season. During the season, there was significant reduction in specific IgE anti-Bet v 1 and anti-t3 (birch pollen extract) levels in the AbM compared with the placebo group. While the maximal allergen concentrations needed for eliciting basophil activation before the season, changed significantly in the placebo group to lower concentrations (i.e., enhanced sensitization) after the season, these concentrations remained similar in the AndosanTM AbM extract group. Hence, the prophylactic effect of oral supplementation before the season with the AbM-based AndosanTM extract on aeroallergen-induced allergy was associated with reduced specific IgE levels during the season and basophils becoming less sensitive to allergen activation.

Annual decline in forced expiratory volume and airway inflammatory cells and mediators in a general population-based sample.

BACKGROUND: Few studies have examined the relationships between sputum inflammatory markers and subsequent annual decline in forced expiratory volume in 1 s (dFEV1). This study investigated whether indices of airway inflammation are predictors of dFEV1 in a general population-based sample. METHODS: The study, conducted from 2003 to 2005, included 120 healthy Norwegian subjects aged 40 to 70 years old. At baseline, the participants completed a self-administered respiratory questionnaire and underwent a clinical examination that included spirometry, venous blood sampling, and induced sputum examination. From 2015 to 2016, 62 (52%) participants agreed to a follow-up examination that did not include induced sputum examination. Those with a FEV1/forced vital capacity (FVC) ratio <  0.70 underwent a bronchial reversibility test. The levels of cytokines, pro-inflammatory M1 macrophage phenotypes were measured in induced sputum using bead-based multiplex analysis. The associations between cytokine levels and dFEV1 were then analysed. RESULTS: The mean dFEV1 was 32.9 ml/year (standard deviation 26.3). We found no associations between dFEV1 and the baseline indices of sputum inflammation. Seven participants had irreversible airflow limitation at follow-up. They had lower FEV1 and gas diffusion at baseline compared with the remaining subjects. Moreover, two of these individuals had a positive reversibility test and sputum eosinophilia at baseline. CONCLUSIONS: In this cohort of presumably healthy subjects, we found no associations between sputum inflammatory cells or mediators and dFEV1 during 10 years of follow-up.

Amphiregulin-producing γδ T cells are vital for safeguarding oral barrier immune homeostasis.

γδ T cells are enriched at barrier sites such as the gut, skin, and lung, where their roles in maintaining barrier integrity are well established. However, how these cells contribute to homeostasis at the gingiva, a key oral barrier and site of the common chronic inflammatory disease periodontitis, has not been explored. Here we demonstrate that the gingiva is policed by γδ T cells with a T cell receptor (TCR) repertoire that diversifies during development. Gingival γδ T cells accumulated rapidly after birth in response to barrier damage, and strikingly, their absence resulted in enhanced pathology in murine models of the oral inflammatory disease periodontitis. Alterations in bacterial communities could not account for the increased disease severity seen in γδ T cell-deficient mice. Instead, gingival γδ T cells produced the wound healing associated cytokine amphiregulin, administration of which rescued the elevated oral pathology of tcrδ-/- mice. Collectively, our results identify γδ T cells as critical constituents of the immuno-surveillance network that safeguard gingival tissue homeostasis.

In vitro preconditioning of insulin-producing cells with growth factors improves their survival and ability to release insulin.

Glucose-induced oxidative stress in the diabetic pancreas directly affects viability and the consequent therapeutic outcome of transplanted stem cells. Pretreatment of stem cells with growth factors induces tolerance in them against various stresses (hypoxia, thermal or hyperglycaemic). This study investigated the effect of pretreatment on insulin-producing cells (IPCs) differentiated from adipose-derived mesenchymal stem cells (ADMSCs), with a combination of stromal cell-derived factor 1 alpha (SDF1 α) and basic fibroblast growth factor (bFGF) against hyperglycaemic stress (17 or 33 mM glucose). The results showed that IPCs pretreated with a combination of SDF1α and bFGF exhibited maximally alleviated apoptosis, senescence and cell damage with a concomitantly increased release of insulin, enhanced cell proliferation and greater upregulation of Insulin 1, Insulin 2, Ngn3, Pdx1 and Nkx6.2 when stressed with 33 mM glucose. These findings may offer an improved therapeutic outcome for the treatment of diabetes.

Relationship of Baseline Hemoglobin Level with Serum Ferritin, Postphlebotomy Hemoglobin Changes, and Phlebotomy Requirements among HFE C282Y Homozygotes.

Objectives. We aimed to examine whether baseline hemoglobin levels in C282Y-homozygous patients are related to the degree of serum ferritin (SF) elevation and whether patients with different baseline hemoglobin have different phlebotomy requirements. Methods. A total of 196 patients (124 males and 72 females) who had undergone therapeutic phlebotomy and had SF and both pre- and posttreatment hemoglobin values were included in the study. Results. Bivariate correlation analysis suggested that baseline SF explains approximately 6 to 7% of the variation in baseline hemoglobin. The results also showed that males who had higher (≥150 g/L) baseline hemoglobin levels had a significantly greater reduction in their posttreatment hemoglobin despite requiring fewer phlebotomies to achieve iron depletion than those who had lower (<150 g/L) baseline hemoglobin, regardless of whether baseline SF was below or above 1000 µg/L. There were no significant differences between hemoglobin subgroups regarding baseline and treatment characteristics, except for transferrin saturation between male subgroups with SF above 1000 µg/L. Similar differences were observed when females with higher (≥138 g/L) baseline hemoglobin were compared with those with lower (<138 g/L) baseline hemoglobin. Conclusion. Dividing C282Y-homozygous patients into just two subgroups according to the degree of baseline SF elevation may obscure important subgroup variations.

Resistance of polio to its eradication in Pakistan.

BACKGROUND: This study is based on EPI (Expanded Program on Immunization) immunization surveys and surveillance of polio, its challenges in immunization and the way forward to overcome these challenges. METHODS: Several Government documents, survey reports and unpublished program documents were studied and online search was made to find information on EPI Pakistan. SPSS 16 and Microsoft Excel 2007 were used for the statistical analysis. RESULTS: Immunization against polio is higher in urban areas as compared to rural areas. Marked variation in vaccination has been observed in different provinces of Pakistan in the last decade. Secondly 10-20% of the children who have received their first dose of trivalent polio vaccine were deprived of their 2nd and 3rd dose because of poor performance of EPI and Lack of information about immunization. CONCLUSION: In spite of numerous successes, such as the addition of new vaccines and raising immunization to over 100% in some areas, EPI is still struggling to reach its polio eradication goals. Inadequate service delivery, lack of information about immunization and limited number of vaccinators were found to be the key reason for poor performance of immunization and for large number of cases reported each year due to the deficiency of second and third booster dose.