Georg M. N. Behrens

Selective depletion of Foxp3+ Treg during sensitization phase aggravates experimental allergic airway inflammation

Recent studies highlight the role of Treg in preventing unnecessary responses to allergens and maintaining functional immune tolerance in the lung. We investigated the role of Treg during the sensitization phase in a murine model of experimental allergic airway inflammation by selectively depleting the Treg population in vivo. DEpletion of REGulatory T cells (DEREG) mice were depleted of Treg by diphtheria toxin injection. Allergic airway inflammation was induced using OVA as a model allergen. Pathology was assessed by scoring for differential cellular infiltration in bronchoalveolar lavage, IgE and IgG1 levels in serum, cytokine secretion analysis of lymphocytes from lung draining lymph nodes and lung histology. Use of DEREG mice allowed us for the first time to track and specifically deplete both CD25+ and CD25− Foxp3+ Treg, and to analyze their significance in limiting pathology in allergic airway inflammation. We observed that depletion of Treg during the priming phase of an active immune response led to a dramatic exacerbation of allergic airway inflammation in mice, suggesting an essential role played by Treg in regulating immune responses against allergens as early as the sensitization phase via maintenance of functional tolerance.

Norovirus outbreaks in german refugee camps in 2015

Purpose Refugees often live in confined housing conditions with shared kitchen and sanitary facilities, rendering susceptible to communicable diseases. We here describe the outbreak, spread and self-limiting nature of a norovirus outbreak in a German refugee camp in the winter of 2015. Methods During a norovirus outbreak, data on clinical symptoms, nationality and living conditions was obtained in a refugee camp in northern Germany in the winter of 2015. Furthermore secondary data on norovirus outbreaks in 2015 was assessed. Results Amongst n = 982 refugees, n = 36 patients (3.7 %) presented with acute norovirus gastroenteritis. The vast majority of cases were children, only the first patient was admitted to the hospital. Intensified hygiene measures were implemented on day 2 of the outbreak, but new cases peaked on day 21 and occurred until one month after the first case. Different cultural backgrounds, eating habits and hygiene standards amongst the refugees made it particularly challenging to implement stringent isolation and hygiene measures. Despite these predisposing factors, only minor norovirus outbreaks were reported in refugee camps in 2015. Conclusion Adults refugees had a low attack rate of symptomatic norovirus infection, while small children are at high risk. Infection spreads despite hygiene measures and camp sites and staff should be prepared for the particular challenges of such situations with a particular focus on cultural-background specific implementation of hygiene measures.

Metabolisches Syndrom und Hyperlipidämie bei HIV-positiven Patienten

ZusammenfassungDie Beeinflussung des Fett- und Glucosestoffwechsels sowie der Körperfettverteilung ist eine häufige unerwünschte Nebenwirkung der Behandlung der HIV-Infektion. Viele Patienten entwickeln während der antiretroviralen Therapie zentrale Kriterien des sog. metabolischen Syndroms wie Insulinresistenz, Dyslipidämie und zentrale Adipositas. Für die Patienten steht die Angst vor physischen Veränderungen durch fazialen Fettverlust im Vordergrund, da diese das Aussehen, das Gefühlsleben und die Lebensqualität belasten. Hinzu kommt die Furcht, die Arzt und Patient teilen: ein erhöhtes kardiovaskuläres Risiko der HIV-Infizierten durch die Therapie. Obwohl neuere Medikamente ein besseres Nebenwirkungsprofil aufweisen, müssen künftig weitere Medikamente entwickelt werden, um die HIV-Infektion effektiv zu behandeln und Langzeitkomplikationen zu ver hindern. Bis dahin gilt es, durch geschickten Einsatz der verfügbaren antiretroviralen Medikamente unerwünschte Nebenwirkungen zu verhindern oder zu verzögern und kardiovaskuläre Risiken zu verringern. Dazu kommen generelle Empfehlungen (Nikotinentwöhnung, körperliche Betätigung), der Wechsel der antiretroviralen Therapie (z. B. Austausch von bestimmten Proteaseinhibitoren) sowie die Therapie mit metabolisch wirksamen Medikamenten zur Senkung der Lipide und Insulinresistenz.AbstractThe HIV lipodystrophy syndrome, a condition characterized by subcutaneous fat loss sometimes associated with relative or absolute accumulation of central fat, has a high prevalence in the treatment of HIV infection. Associated metabolic alterations include peripheral and hepatic insulin resistance, impaired glucose tolerance, type 2 diabetes, hypertriglyceridemia, hypercholesterolemia, increased free fatty acids, and decreased HDL. Often, these metabolic abnormalities appear or deteriorate before the manifestation of fat redistribution. Hypertriglyceridemia is the leading lipid abnormality after initiation of HIV therapy frequently observed together with low HDL cholesterol. Raised levels of tissue plasminogen activator and plasminogen activator inhibitor-1 have been found in these patients, and there are reports about hypertension associated with antiretroviral therapy. Thus, the lipodystrophy syndrome in HIV therapy resembles a clinical situation that is known as the “metabolic syndrome” in HIV-negative patients. There is now good evidence that the metabolic abnormalities of HIV-infected patients harbor a significant risk for cardiovascular disease with as yet unknown consequences. In addition, several studies report a reduced quality of life in patients with body habitus changes leading to reduced therapy adherence. Current data indicate a rather multifactorial pathogenesis where HIV infection, its therapy, and patient-related factors are major contributors. Therapeutic and preventive strategies have, so far, been of only limited or no success. For reduction of the cardiovascular risk, recommendations proposed for non-HIV-infected patients like the National Cholesterol Education Program (NECP) have been adapted for HIV-infected patients. These should be regarded as rather preliminary and need to be evaluated in further clinical trials. General recommendations include dietary changes and physical activity, switch of antiretroviral drugs (replacement of protease inhibitors), and, finally, use of metabolically active drugs. Lipid-lowering agents can be considered for the treatment of severe hypertriglyceridemia, elevated LDL, or a combination of both. Some HMG-CoA reductase inhibitors, however, share common hepatic metabolization pathways with protease inhibitors (cytochrome P450 3A4 system), thereby potentially leading to additional liver and muscle toxicity. Although clinicians should assess cardiovascular risk factors and target risk reduction in HIV-infected patients, the primary goal in HIV therapy remains to be the effective suppression of viral replication leading to reduced morbidity and mortality.

HIV-Immunologie: Gewinnt am Ende immer das Virus?

Die chronische Immunaktivierung ist eine charakteristische Eigenschaft der progressiven HIV-Erkrankung. Insbesondere die polyklonale B-Zell-Aktivierung war eine der ersten immunologischen Veranderungen, die bei HIV-Patienten diagnostiziert wurde. Spater wurden vermehrter T-Zell-Umsatz, eine vermehrte Frequenz von T-Zellen mit aktiviertem Phanotyp und auch erhohte Serumspiegel fur proinflammatorische Zytokine und Chemokine festgestellt. Es ist bemerkenswert, dass der Grad an Immunaktivierung ein besserer Pradiktor fur die Erkrankungsprogredienz ist, als die Viramie. War die Ursache fur die Immunaktivierung bisher unklar, so haben wir in den letzten Jahren insbesondere neue Erkenntnisse uber den zeitlichen Verlauf und die anatomische Lokalisation der pathogenetischen Ereignisse der HIV-Infektion gewonnen.

Metabolisches Syndrom und Hyperlipidämie bei HIV-positiven Patienten@@@Metabolic Syndrome and Hyperlipidemia in HIV-Positive Patients

ZusammenfassungDie Beeinflussung des Fett- und Glucosestoffwechsels sowie der Körperfettverteilung ist eine häufige unerwünschte Nebenwirkung der Behandlung der HIV-Infektion. Viele Patienten entwickeln während der antiretroviralen Therapie zentrale Kriterien des sog. metabolischen Syndroms wie Insulinresistenz, Dyslipidämie und zentrale Adipositas. Für die Patienten steht die Angst vor physischen Veränderungen durch fazialen Fettverlust im Vordergrund, da diese das Aussehen, das Gefühlsleben und die Lebensqualität belasten. Hinzu kommt die Furcht, die Arzt und Patient teilen: ein erhöhtes kardiovaskuläres Risiko der HIV-Infizierten durch die Therapie. Obwohl neuere Medikamente ein besseres Nebenwirkungsprofil aufweisen, müssen künftig weitere Medikamente entwickelt werden, um die HIV-Infektion effektiv zu behandeln und Langzeitkomplikationen zu ver hindern. Bis dahin gilt es, durch geschickten Einsatz der verfügbaren antiretroviralen Medikamente unerwünschte Nebenwirkungen zu verhindern oder zu verzögern und kardiovaskuläre Risiken zu verringern. Dazu kommen generelle Empfehlungen (Nikotinentwöhnung, körperliche Betätigung), der Wechsel der antiretroviralen Therapie (z. B. Austausch von bestimmten Proteaseinhibitoren) sowie die Therapie mit metabolisch wirksamen Medikamenten zur Senkung der Lipide und Insulinresistenz.AbstractThe HIV lipodystrophy syndrome, a condition characterized by subcutaneous fat loss sometimes associated with relative or absolute accumulation of central fat, has a high prevalence in the treatment of HIV infection. Associated metabolic alterations include peripheral and hepatic insulin resistance, impaired glucose tolerance, type 2 diabetes, hypertriglyceridemia, hypercholesterolemia, increased free fatty acids, and decreased HDL. Often, these metabolic abnormalities appear or deteriorate before the manifestation of fat redistribution. Hypertriglyceridemia is the leading lipid abnormality after initiation of HIV therapy frequently observed together with low HDL cholesterol. Raised levels of tissue plasminogen activator and plasminogen activator inhibitor-1 have been found in these patients, and there are reports about hypertension associated with antiretroviral therapy. Thus, the lipodystrophy syndrome in HIV therapy resembles a clinical situation that is known as the “metabolic syndrome” in HIV-negative patients. There is now good evidence that the metabolic abnormalities of HIV-infected patients harbor a significant risk for cardiovascular disease with as yet unknown consequences. In addition, several studies report a reduced quality of life in patients with body habitus changes leading to reduced therapy adherence. Current data indicate a rather multifactorial pathogenesis where HIV infection, its therapy, and patient-related factors are major contributors. Therapeutic and preventive strategies have, so far, been of only limited or no success. For reduction of the cardiovascular risk, recommendations proposed for non-HIV-infected patients like the National Cholesterol Education Program (NECP) have been adapted for HIV-infected patients. These should be regarded as rather preliminary and need to be evaluated in further clinical trials. General recommendations include dietary changes and physical activity, switch of antiretroviral drugs (replacement of protease inhibitors), and, finally, use of metabolically active drugs. Lipid-lowering agents can be considered for the treatment of severe hypertriglyceridemia, elevated LDL, or a combination of both. Some HMG-CoA reductase inhibitors, however, share common hepatic metabolization pathways with protease inhibitors (cytochrome P450 3A4 system), thereby potentially leading to additional liver and muscle toxicity. Although clinicians should assess cardiovascular risk factors and target risk reduction in HIV-infected patients, the primary goal in HIV therapy remains to be the effective suppression of viral replication leading to reduced morbidity and mortality.