Background: The development of safe and effective immunotherapy for peanut allergy has been complicated by the high anaphylactic potential of native peanut extracts. We sought to map the T‐cell epitopes of the major peanut allergen, Ara h 2 in order to develop T‐cell targeted vaccines. Methods: A panel of eight peanut‐specific CD4+ T‐cell lines (TCL) was derived from eight peanut‐allergic subjects and proliferative and cytokine responses to stimulation with a set of overlapping 20‐mer peptides representing the entire sequence of Ara h 2 determined. Proliferation was assessed in 72 h assays via tritiated thymidine incorporation, while interleukin (IL)‐5 and interferon (IFN)‐ γ production were assessed via sandwich enzyme‐linked immunosorbent assay (ELISA) of cell culture supernatants. Results: Eight of the 17 Ara h 2 peptides were recognized by one or more subjects, with the two peptides showing highest reactivity [Ara h 2 (19–38) and Ara h 2 (73–92)] being recognized by three subjects each. Adjoining peptides Ara h 2 (28–47) and Ara h 2 (100–119) induced proliferative responses in two subjects. Each of these peptides was associated with a Th2‐type cytokine response. Conclusion: Two highly immunogenic T‐cell reactive regions of Ara h 2 have been identified, Ara h 2 (19–47) and Ara h 2 (73–119), providing scope for the development of safe forms of immunotherapy for peanut allergy.
Inborn errors affecting components of the T-cell receptor signaling cascade cause combined immunodeficiency with various degrees of severity. Recently, homozygous variants in LCP2 were reported to cause pediatric onset of severe combined immunodeficiency with neutrophil, platelet, and T- and B-cell defects.We sought to unravel the genetic cause of combined immunodeficiency and early-onset immune dysregulation in a 26-year-old man who presented with specific antibody deficiency, autoimmunity, and inflammatory bowel disease since early childhood.The patient was subjected to whole-exome sequencing of genomic DNA and examination of blood neutrophils, platelets, and T and B cells. Expression levels of the Src homology domain 2-containing leukocyte protein of 76 kDa (SLP76) and tonic and ligand-induced PI3K signaling were evaluated by flow-cytometric detection of phosphorylated ribosomal protein S6 in B and T cells.Compound heterozygous missense variants were identified in LCP2, affecting the proline-rich repeat domain of SLP76 (p.P190R and p.R204W). The patient's total B- and T-cell numbers were within the normal range, as was platelet function. However, neutrophil function, numbers of unswitched and class-switched memory B cells, and serum IgA were decreased. Moreover, intracellular SLP76 protein levels were reduced in the patient's B cells, CD4+ and CD8+ T cells, and natural killer cells. Tonic and ligand-induced levels of phosphorylated ribosomal protein S6 and ligand-induced phosphorylated PLCγ1 were decreased in the patient's B cells and CD4+ and CD8+ T cells.Biallelic variants in LCP2 impair neutrophil function and T-cell and B-cell antigen-receptor signaling and can cause combined immunodeficiency with early-onset immune dysregulation, even in the absence of platelet defects.
<b><i>Background:</i></b> Bahia grass pollen (BaGP) is a major cause of allergic rhinitis. Subcutaneous allergen-specific immunotherapy is effective for grass pollen allergy, but is unsuitable for patients with moderate to severe asthma due to the risk of anaphylaxis. T cell-reactive but IgE nonreactive peptides provide a safer treatment option. This study aimed to identify and characterize dominant CD4<sup>+</sup> T cell epitope peptides of the major BaGP allergen, Pas n 1. <b><i>Methods:</i></b> Pas n 1-specific T cell lines generated from the peripheral blood of BaGP-allergic subjects were tested for proliferative and cytokine response to overlapping 20-mer Pas n 1 peptides. Cross-reactivity to homologous peptides from Lol p 1 and Cyn d 1 of Ryegrass and Bermuda grass pollen, respectively, was assessed using Pas n 1 peptide-specific T cell clones. MHC class II restriction of Pas n 1 peptide T cell recognition was determined by HLA blocking assays and peptide IgE reactivity tested by dot blotting. <b><i>Results:</i></b> Three Pas n 1 peptides showed dominant T cell reactivity; 15 of 18 (83%) patients responded to one or more of these peptides. T cell clones specific for dominant Pas n 1 peptides showed evidence of species-specific T cell reactivity as well as cross-reactivity with other group 1 grass pollen allergens. The dominant Pas n 1 T cell epitope peptides showed HLA binding diversity and were non-IgE reactive. <b><i>Conclusions:</i></b> The immunodominant T cell-reactive Pas n 1 peptides are candidates for safe immunotherapy for individuals, including those with asthma, who are allergic to Bahia and possibly other grass pollens.
Objective: To evaluate the effectiveness of a multifaceted educational intervention for general practitioners to improve the outcomes of older people with asthma. Design: Cluster randomised controlled trial. Participants and setting: 42 GPs recruited from metropolitan Melbourne between 1 August 2006 and 31 July 2007, randomly assigned to an intervention or control group, and 107 patients with asthma, aged 55 years or older (consecutive patients recruited by the GPs). Main outcome measures: Evaluation by means of a videorecorded consultation with a simulated patient for GPs; and for patients, asthma control and quality of life, lung function and action plan ownership at baseline and at 4 months. Results: GPs in the intervention group scored significantly higher than those in the control group for the content and style of their consultation with simulated patients. At 4 months’ follow-up, there was no significant difference between patient groups in the asthma control scores, asthma-related quality of life or lung function. Conclusion: This trial showed an improvement in GPs’ performance in delivering asthma care to older people. Despite this, there was no significant improvement in patient outcomes. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12607000634471.
Abstract In December 2019, China reported the first cases of the coronavirus disease 2019 (COVID‐19). This disease, caused by the severe acute respiratory syndrome–related coronavirus 2 (SARS‐CoV‐2), has developed into a pandemic. To date, it has resulted in ~9 million confirmed cases and caused almost 500 000 related deaths worldwide. Unequivocally, the COVID‐19 pandemic is the gravest health and socioeconomic crisis of our time. In this context, numerous questions have emerged in demand of basic scientific information and evidence‐based medical advice on SARS‐CoV‐2 and COVID‐19. Although the majority of the patients show a very mild, self‐limiting viral respiratory disease, many clinical manifestations in severe patients are unique to COVID‐19, such as severe lymphopenia and eosinopenia, extensive pneumonia, a “cytokine storm” leading to acute respiratory distress syndrome, endothelitis, thromboembolic complications, and multiorgan failure. The epidemiologic features of COVID‐19 are distinctive and have changed throughout the pandemic. Vaccine and drug development studies and clinical trials are rapidly growing at an unprecedented speed. However, basic and clinical research on COVID‐19–related topics should be based on more coordinated high‐quality studies. This paper answers pressing questions, formulated by young clinicians and scientists, on SARS‐CoV‐2, COVID‐19, and allergy, focusing on the following topics: virology, immunology, diagnosis, management of patients with allergic disease and asthma, treatment, clinical trials, drug discovery, vaccine development, and epidemiology. A total of 150 questions were answered by experts in the field providing a comprehensive and practical overview of COVID‐19 and allergic disease.
Atopic eczema, allergic broncho‐pulmonary aspergillosis, helminthic infections and rare primary immunodeficiencies are known to elevate total serum immunoglobulin E ( IgE ) above 1000 IU / mL . However, of 352 patients with IgE >1000 IU / mL seen in our hospital over a 5‐year period, less than 50% had these conditions. Markedly elevated IgE levels in the rest of the patients were associated with asthma, allergic rhinitis and food allergy, instances where the test is of limited diagnostic utility.