Allergen-Specific Antibodies Regulate Secondary Allergen-Specific Immune Responses

Immunoglobulin E (IgE)-associated allergy is the most common immunologically-mediated hypersensensitivity disease. It is based on the production of IgE antibodies and T cell responses against per se innocuous antigens (i.e., allergens) and subsequent allergen-induced inflammation in genetically pre-disposed individuals. While allergen exposure in sensitized subjects mainly boosts IgE production and T cell activation, successful allergen-specific immunotherapy (AIT) induces the production of allergen-specific IgG antibodies and reduces T cell activity. Under both circumstances, the resulting allergen-antibody complexes play a major role in modulating secondary allergen-specific immune responses: Allergen-IgE complexes induce mast cell and basophil activation and perpetuate allergen-specific T cell responses via presentation of allergen by allergen presenting cells to T cells, a process called IgE-facilitated antigen presentation (FAP). In addition, they may induce activation of IgE memory B cells. Allergen-induced production of specific IgGs usually exerts ameliorating effects but under certain circumstances may also contribute to exacerbation. Allergen-specific IgG antibodies induced by AIT which compete with IgE for allergen binding (i.e., blocking IgG) inhibit formation of IgE-allergen complexes and reduce activation of effector cells, B cells and indirectly T cells as FAP is prevented. Experimental data provide evidence that by binding of allergen-specific IgG to epitopes different from those recognized by IgE, allergen-specific IgG may enhance IgE-mediated activation of mast cells, basophils and allergen-specific IgE+ B cells. In this review we provide an overview about the role of allergen-specific antibodies in regulating secondary allergen-specific immune responses

Nasal IL-13 production identifies patients with late phase allergic responses

BACKGROUND: There is limited knowledge on how local cytokine secretion patterns after nasal allergen challenge correlate with clinical symptoms especially with regards to the "late allergic response" (LAR) which occurs in approximately 40-50% of allergic patients. OBJECTIVE: In this study we aimed to characterise the immunological and clinical nasal responses to birch pollen allergen challenge with a special focus on the LAR. METHODS: In this randomised double-blinded placebo-control trial, birch pollen allergic participants were challenged with pollen extract (n=20) or placebo (n=10) on three consecutive days. On days one and three nasal secretions were collected at selected time points over a 24h time course for the measurement of 33 inflammatory mediators. Clinical responses were determined through subjective symptom scores and objective nasal airflow measurements. RESULTS: Provoked participants had significantly greater clinical responses and showed significant increases in tryptase and sST2 within minutes compared to placebo. Eight out of 20 provoked participants displayed high IL-13 levels 2-8 hours after allergen provocation. This group also showed significant changes in clinical parameters, with a secondary drop in nasal airflow measured by peak nasal inspiratory flow and increased symptoms of nasal obstruction which significantly differed from IL-13 non responders at 6 hours. CONCLUSION: IL-13 response status correlates with cytokine and clinical responses in the late phase after allergen provocation

Is diet partly responsible for differences in COVID-19 death rates between and within countries?

Correction: Volume: 10 Issue: 1 Article Number: 44 DOI: 10.1186/s13601-020-00351-w Published: OCT 26 2020Reported COVID-19 deaths in Germany are relatively low as compared to many European countries. Among the several explanations proposed, an early and large testing of the population was put forward. Most current debates on COVID-19 focus on the differences among countries, but little attention has been given to regional differences and diet. The low-death rate European countries (e.g. Austria, Baltic States, Czech Republic, Finland, Norway, Poland, Slovakia) have used different quarantine and/or confinement times and methods and none have performed as many early tests as Germany. Among other factors that may be significant are the dietary habits. It seems that some foods largely used in these countries may reduce angiotensin-converting enzyme activity or are anti-oxidants. Among the many possible areas of research, it might be important to understand diet and angiotensin-converting enzyme-2 (ACE2) levels in populations with different COVID-19 death rates since dietary interventions may be of great benefit.Peer reviewe

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.Peer reviewe

Use of biologicals in allergic and type 2 inflammatory diseases in the current COVID-19 pandemic

Hintergrund: Die Behandlung von Patienten mit Allergien und atopieassoziierten Erkrankungen wurde seit Beginn der ­COVID-19-Pandemie vor große Herausforderungen gestellt. Empfehlungen zum „social distancing“ und die Angst der Patienten vor einer Infektion in medizinischen Einrichtungen haben zu einer drastischen Abnahme der persönlichen Arzt-Patienten-Kontakte geführt. Hiervon sind Akutversorgung und Behandlung chronisch Kranker gleichermaßen betroffen. Die Immunantwort nach SARS-CoV-2-Infektion ist bislang nur unzureichend bekannt und könnte durch eine Therapie mit monoklonalen Antikörpern günstig aber auch ungünstig verändert werden. Zum jetzigen Zeitpunkt bestehen keine Hinweise auf ein erhöhtes Risiko von Allergikern für einen schwereren COVID-19-Krankheitsverlauf. Zahlreiche Patientinnen und Patienten befinden sich unter laufender Therapie mit Biologika, die über verschiedene Ansätze Typ 2 Immunantworten inhibieren. Es besteht Unklarheit über mögliche immunologische Interaktionen und potenzielle Risiken dieser Biologika im Falle einer Infektion mit SARS-CoV-2. Methodik: Für die vorliegende Publikation wurde eine selektive Literaturrecherche in PubMed, Livivo und im World Wide Web für die zurückliegenden 10 Jahre (Zeitraum Mai 2010 – April 2020) durchgeführt. Darüber hinaus wurden hier die aktuellen, dort nicht enthaltenen deutschsprachigen Publikationen analysiert. Auf Grundlage dieser Daten gibt dieses Positionspapier Empfehlungen für die Behandlung mit Biologika bei Patienten mit allergischen und Atopie assoziierten Erkrankungen in der COVID-19-Pandemie. Ergebnisse: Zur Aufrechterhaltung von Präsenzsprechstunden muss eine sichere und an die Pandemiesituation adaptierte Behandlungsumgebung geschaffen werden. Verlässliche Studiendaten zur Versorgung komplex erkrankter Atemwegs-, Atopie- und Allergiepatienten in Zeiten imminenter Infektionsgefahr durch SARS-CoV-2 fehlen bis dato. Typ-2-geprägte Immunreaktionen, wie sie bei Allergiepatienten oft vorliegen, könnten auf die verschiedenen Phasen von ­COVID-19 Einfluss nehmen, indem sie beispielsweise Immun­reaktionen bremsen. Das könnte sich theoretisch in der frühen Phase der SARS-Cov-2 Infektion ungünstig, in der späten Phase schwerer Verläufe während eines „cytokine storm“ (Zytokinsturm) günstig auswirken. Da es dafür bisher aber keine Belege gibt, sollten alle Daten von Patienten unter einem gegen Typ-2 Immunreaktionen gerichteten Biologikum, die an COVID-19 erkranken, in Registern gesammelt und ihre Krankheitsverläufe dokumentiert werden, um in Zukunft erfahrungsbasierte Handlungsanweisungen geben zu können. Schlussfolgerung: Die Therapie mit Biologika zur Behandlung von Asthma bronchiale, atopischer Dermatitis, chronischer Rhinosinusitis mit Nasenpolypen und spontaner Urtikaria sollte in der aktuellen COVID-19-Pandemie bei Patienten ohne Infektionsverdacht oder nachgewiesene SARS-CoV-2 Infektion unverändert fortgesetzt werden. Falls verfügbar ist es empfehlenswert, eine Formulierung zur Eigenapplikation zu bevorzugen und ein telemedizinisches Monitoring anzubieten. Behandlungsziel sollte sein, schwer kontrollierbare allergische und atopische Erkrankungen durch angemessene Bedarfs- und Add-on-Therapie bestmöglich einzustellen und die Notwendigkeit systemischer Glukokortikosteroide zu vermeiden. Im Falle eines begründeten Verdachts oder einer nachgewiesenen Infektion mit SARS-CoV-2 sollte die Therapie individuell durch Abwägung von Nutzen und Risiken als Einzelfallentscheidung unter Einbeziehung des Patienten bestimmt werden. Hierbei ist zu bedenken, dass mögliche Einflüsse von Biologika auf die Immunantwort bei COVID-19 aktuell nicht genau bekannt sind. Telemedizinische Angebote sind insbesondere für akuten Beratungsbedarf bei geeigneten Patienten wünschenswert