This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

IgG4 subclass antibodies are expressed in alternative Th2 environments featuring high IL-10 expression, including several solid tumors such as melanoma. To induce tolerance, allergen immunotherapy mediates antibody class switching from pro-inflammatory IgE to anti-inflammatory IgG4. We previously reported that IgG4 drives allergic M2 macrophages toward tolerogenic states. Here we assessed the roles of IgG4 and macrophage activation in colorectal cancer (CRC). In this observer-blinded, case-control study, we analyzed total circulating serum IgE, IgG1 and IgG4 levels in CRC (n = 38) patients with (n = 13, TxNxM1) or without (n = 25, TxNxM0) metastasis, and in healthy donors (n = 21). Primary cultures of circulating monocyte-derived macrophages from healthy controls and CRC patients were further evaluated in their responses to stimulation with IgG1 or IgG4. We found higher absolute serum levels of IgG4 in patients with CRC. IgG4 enabled polarization of macrophages derived from CRC patients and healthy controls into alternatively-activated tolerogenic M2b phenotypes. IgG4-stimulated M2 macrophages were characterized by lower surface CD206, CD163, CD14, and CD11b expression and higher CCL-1, IL-10, and IL-6 production. IgG4 was less potent that IgG1 in triggering antibody-dependent cell-mediated phagocytosis (ADCP) of cancer cells. Further, higher z-normalized IgG4/-IgE sera level ratios correlated with the presence of metastasis ( p = .0247 and p = .0009, respectively) in CRC patients. High IgG4 in CRC synergizes with macrophages in shaping an immunosuppressive microenvironment and impairs anti-cancer effector cell functions. The shift of serum IgG4/IgE ratios toward enhanced tolerance induction in metastatic disease indicates a role for high IgG4 in disease progression and poor prognostic outcome.

equally contributed.This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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The numbers of reptiles in homes has at least doubled in the last decade in Europe and the USA. Reptile purchases are increasingly triggered by the attempt to avoid potentially allergenic fur pets like dogs and cats. Consequently, reptiles are today regarded as surrogate pets initiating a closer relationship with the owner than ever previously observed. Reptile pets are mostly fed with insects, especially grasshoppers and/or locusts, which are sources for aggressive airborne allergens, best known from occupational insect breeder allergies. Exposure in homes thus introduces a new form of domestic allergy to grasshoppers and related insects. Accordingly, an 8-year old boy developed severe bronchial hypersensitivity and asthma within 4 months after purchase of a bearded dragon. The reptile was held in the living room and regularly fed with living grasshoppers. In the absence of a serological allergy diagnosis test, an IgE immunoblot on grasshopper extract and prick-to-prick test confirmed specific sensitization to grasshoppers. After 4 years of allergen avoidance, a single respiratory exposure was sufficient to trigger a severe asthma attack again in the patient.Based on literature review and the clinical example we conclude that reptile keeping is associated with introducing potent insect allergens into home environments. Patient interviews during diagnostic procedure should therefore by default include the question about reptile pets in homes.

The population of elderly people in the European Union currently ranges from 12.2% (Ireland) to 20.6% (Germany). 1 Germany, with 17 million elderly people, thus currently represents the European country with the oldest population, and this cohort will increase to approximately 23.4 million by 2050. 1 According to the US Census Bureau, 2 in the United States approximately 47 million (15%) of the population are currently older than 65 years. It is moreover expected that the US population will become significantly older and reach 83.7 million people older than 65 years in 2050 (ie, 20% of the population). Notably, similar trends are expected in this report for all industrial countries. In all instances, the proportion of people older than 85 years will also significantly increase. From this, it can be expected that the new situation will challenge policymakers and health care professionals. In parallel with these changes, we may expect that the occurrence of allergies will also increase in the elderly cohort, especially considering environmental challenges.

Background In allergology practice, efficient counselling of cat owners is often frustrating because the topic of allergen avoidance is mostly a “no-go” and there are only few studies on allergen immunotherapy that prove its efficacy. In the end, what patients are mostly offered in allergy consultations are allergen reduction measures and symptomatic therapy. Results Sensitisation to the main cat allergen Fel d 1 occurs more frequently in atopic conditions and then represents a risk for allergic rhinitis and asthma. Current guidelines are therefore cautious about the first-time acquisition of a cat in the first months of life in atopic families. However, sensitisation occurs in many cases even without contact with an own cat at home. Conversely, it has been observed in adult patients that in the case of high Fel d 1 exposure immunological tolerance can also develop through the induction of specific IgG4. The fact that many cat allergic patients keep their animals despite diagnosis is, however, partly due to the psychological phenomenon of coping. Conclusion In this review, we present current literature and facts that should make everyday life easier for patients, even without giving up the animal. We also review best practices in the management of cat allergy and present new management options and concepts from the development pipeline that our patients are eagerly awaiting.