Prevention of Birch Pollen-Related Food Allergy by Mucosal Treatment with Multi-Allergen-Chimers in Mice

Among birch pollen allergic patients up to 70% develop allergic reactions to Bet v 1-homologue food allergens such as Api g 1 (celery) or Dau c 1 (carrot), termed as birch pollen-related food allergy. In most cases, specific immunotherapy with birch pollen extracts does not reduce allergic symptoms to the homologue food allergens. We therefore genetically engineered a multi-allergen chimer and tested if mucosal treatment with this construct could represent a novel approach for prevention of birch pollen-related food allergy.BALB/c mice were poly-sensitized with a mixture of Bet v 1, Api g 1 and Dau c 1 followed by a sublingual challenge with carrot, celery and birch pollen extracts. For prevention of allergy sensitization an allergen chimer composed of immunodominant T cell epitopes of Api g 1 and Dau c 1 linked to the whole Bet v 1 allergen, was intranasally applied prior to sensitization.Intranasal pretreatment with the allergen chimer led to significantly decreased antigen-specific IgE-dependent β-hexosaminidase release, but enhanced allergen-specific IgG2a and IgA antibodies. Accordingly, IL-4 levels in spleen cell cultures and IL-5 levels in restimulated spleen and cervical lymph node cell cultures were markedly reduced, while IFN-γ levels were increased. Immunomodulation was associated with increased IL-10, TGF-β and Foxp3 mRNA levels in NALT and Foxp3 in oral mucosal tissues. Treatment with anti-TGF-β, anti-IL10R or anti-CD25 antibodies abrogated the suppression of allergic responses induced by the chimer.Our results indicate that mucosal application of the allergen chimer led to decreased Th2 immune responses against Bet v 1 and its homologue food allergens Api g 1 and Dau c 1 by regulatory and Th1-biased immune responses. These data suggest that mucosal treatment with a multi-allergen vaccine could be a promising treatment strategy to prevent birch pollen-related food allergy

Gastroesophageal reflux disease is associated with a more severe interstitial lung disease in systemic sclerosis in the EUSTAR cohort

Objectives Gastroesophageal reflux disease (GERD) is frequent in systemic sclerosis (SSc) and could predict progression of interstitial lung disease (ILD). We aimed to analyse (1) the prevalence of GERD among SSc-ILD patients, (2) its association with disease characteristics and (3) predictive factors for ILD progression in SSc-ILD patients with GERD. Methods SSc patients from the EUSTAR database with ILD were included. GERD was labelled as present if reflux/dysphagia was reported at the baseline visit or before. Disease characteristics of patients with and without GERD were compared at baseline. ILD progression was defined as relative FVC decline ≥10% or relative FVC decline between 5–9% in association with relative DLCO decline of ≥15% over 12 ± 3 months of follow-up. Prognostic factors for ILD progression, overall survival and progression-free survival in SSc-ILD patients with GERD were tested by multivariable Cox regression. Results A total of 5462 SSc-ILD patients were included, 4400 (80.6%) had GERD. Patients with GERD presented more frequently with diffuse cutaneous SSc (OR: 1.44 [1.22–1.69], P < 0.001) and more severe lung involvement with lower FVC (85.8 ± 22.1 vs 90.2 ± 20.1, P < 0.001), lower DLCO (60.8 ± 19.7 vs 65.3 ± 20.6, P < 0.001) and worse performance at the 6-min walking test. Female sex (HR: 1.39 [1.07–1.80], P = 0.012) and older age (HR: 1.02 [1.01–1.03], P < 0.001) independently predicted ILD progression in SSc-ILD patients with GERD. Conclusion SSc-ILD patients with GERD appear to suffer from a more severe SSc disease. In this population, female sex may be considered a risk factor for ILD progression

Birch pollen-related food allergy: clinical aspects and the role of allergen-specific IgE and IgG4 antibodies

Birch pollen-related food allergy is highly prevalent and often perennial. High food allergen-specific IgG(4)/IgE ratios seem associated with food tolerance, potentially because specific IgG(4) blocks IgE binding to food allergens. Thus, the presence of food allergen-specific IgG(4) antibodies is no diagnostic marker for birch pollen-related food allergy

Evidence of Immunogenic Cell Death (ICD) and ICD-dependent Dendritic Cell Activation Induced by Extracorporeal Photopheresis in Patients with leukemic forms of cutaneous T cell lymphoma.

Despite novel therapeutic options, the long-term management of cutaneous T cell lymphoma (CTCL) remains challenging. Extracorporeal photopheresis (ECP) is an immunomodulating photochemotherapy associated with higher overall survival when used for the treatment of leukemic forms of CTCL. Its exact mode of action is not fully elucidated. Immunogenic cell death (ICD) is pivotal in cancer immunotherapy, marked by the release of damage-associated molecular patterns that enhance dendritic cell (DC) maturation and cytotoxic T lymphocyte responses. This study explores ICD in patients with leukemic forms of CTCL during ECP and its effect on DC activation. We conducted in vitro studies with peripheral blood mononuclear cells (PBMCs) from healthy donors and ex vivo experiments with white blood cells (WBCs) from patients with leukemic forms of CTCL undergoing ECP. We assessed cell viability, apoptosis, and ICD markers (ATP, HMGB1, calreticulin) using flow cytometry, ELISA, and qPCR. Engulfment assays evaluated DC activation by ECP-treated CD4+ T cells. ECP-treated healthy PBMCs and WBCs from patients with leukemic forms of CTCL showed significant induction of ICD hallmarks, including ATP release, HMGB1 secretion, and calreticulin surface exposure. In the patients with leukemic forms of CTCL, calreticulin expression was mainly present in CD4+CD26- T cells, indicating greater ICD susceptibility of malignant T cells. ECP-treated CD4+ T cells were phagocytosed by DCs, a process which we found to be dependent on ICD signals. ECP induces ICD in malignant T cells and, to a lesser extent, in healthy T cells, facilitating DC activation. These findings suggest that ECP enhances targeted immune responses against malignant T cells in leukemic forms of CTCL, offering new insights into its therapeutic mechanisms and potential applications in cancer immunotherapy