Multilingual Children’s Motivations to Code-Switch: A Qualitative Analysis of Code-Switching in Dutch-English Bilingual Daycares

This paper investigates code-switching in young multilingual children through a qualitative analysis. Our aim was to examine which types of code-switches occur and to categorize these in terms of children’s motivations for code-switching. Data were collected from 70 children aged two to three years who attended Dutch-English daycare in the Netherlands where teachers adopted a one-teacher-one-language approach. We observed seven types of code-switches. Motivations for code-switching related to social, metalinguistic, lexical, or conversational factors. These data indicate that young children can tailor their language choices towards the addressee, suggesting a certain level of meta-linguistic awareness and perspective taking. Implications for computational approaches are discussed

HSP: Bystander Antigen in Atopic Diseases?

Over the last years insight in the complex interactions between innate and adaptive immunity in the regulation of an inflammatory response has increased enormously. This has revived the interest in stress proteins; proteins that are expressed during cell stress. As these proteins can attract and trigger an immunological response they can act as important mediators in this interaction. In this respect, of special interest are proteins that may act as modulators of both innate and adaptive immunity. Heat shock proteins (HSPs) are stress proteins that have these, and more, characteristics. More than two decades of studies on HSPs has revealed that they are part of intrinsic, “natural” mechanisms that steer inflammation. This has provoked comprehensive explorations of the role of HSPs in various human inflammatory diseases. Most studies have focused on classical autoimmune diseases. This has led to the development of clinical studies with HSPs that have shown promise in Phase II/III clinical trials. Remarkably, only very little is yet known of the role of HSPs in atopic diseases. In allergic disease a number of studies have investigated the possibility that allergen-specific regulatory T cell (Treg) function is defective in individuals with allergic diseases. This raises the question whether methods can be identified to improve the Treg repertoire. Studies from other inflammatory diseases have suggested HSPs may have such a beneficial effect on the T cell repertoire. Based on the immune mechanisms of atopic diseases, in this review we will argue that, as in other human inflammatory conditions, understanding immunity to HSPs is likely also relevant for atopic diseases. Specifically, we will discuss why certain HSPs such as HSP60 connect the immune response to environmental antigens with regulation of the inflammatory response. Thus they provide a molecular link that may eventually even help to better understand the immune pathological basis of the hygiene hypothesis

Cutaneous vasculitis in children: A nationwide epidemiological study in Spain [version 1; referees: 1 approved]

Background: Cutaneous vasculitis (CV) are a complex group of conditions in children, of which IgA vasculitis (IgAV) is the most common. The objectives of the current study are to describe the incidence of CV in Spain and to analyze the temporal trend in the last 11 years, as well as it seasonal distribution. Methods: Hospital discharges of patients aged 0-18 years with a diagnosis consistent with CV in Spain from 2005 to 2015 were collected from the Spanish National Institute of Statistics (INE) databases. Results: A total of 7304 patients from January 2005 to December 2015 were included; 6991 patients (95%) had a diagnosis of IgAV. The yearly incidence in the whole group was 7.7 per 100,000. Mean age at diagnoses was 6±3 years and 52% were male. The highest rate of admissions was found in the 5-9 year-old group, followed by those with 0-4 years of age (15.7 and 9.0 admissions per 100.000, respectively). Admissions due to CV followed an annual cyclic pattern, with the highest number of daily admissions during fall and winter months and the lowest number in summer months. There was an overall downwards trend of the number of hospital admissions during the period of study, in both males and females (p=0.01). Conclusions: We have estimated an incidence of a 7.7 cases per 100,000 CV in children in Spain. CV-related hospitalization rates have a marked seasonal pattern, with a peak in fall and winter and a nadir in summer months. Children between 5 and 9 years of age are most frequently affected. There is a decreasing trend in CV-related hospitalization, the causes of which should be further assessed

Identification of Natural Bispecific Antibodies against Cyclic Citrullinated Peptide and Immunoglobulin G in Rheumatoid Arthritis

BACKGROUND: Previous studies indicate that natural bispecific antibodies can be readily produced in vivo when the body is simultaneously stimulated with 2 distinct antigens. Patients with rheumatoid arthritis (RA) usually exhibit persistent immune responses to various autoantigens, raising the possibility that natural bispecific antibodies against 2 distinct autoantigens might exist. METHODOLOGY/PRINCIPAL FINDINGS: We identified the presence of natural bispecific antibodies against cyclic citrullinated peptide (CCP) and immunoglobulin G (IgG) in RA patients' sera by means of a double-antigen sandwich enzyme-linked immunosorbent assay (ELISA). The spontaneous emergence of bispecific antibodies was confirmed by mixing different proportions of 1 anti-CCP-positive serum and 1 rheumatoid factor (RF)-positive serum in vitro. Among the tested samples, positive correlations were found between the presence of bispecific antibodies and both IgG4 anti-CCP antibodies and IgG4 RF (r = 0.507, p<0.001 and r = 0.249, p = 0.044, respectively), suggesting that the IgG4 subclass is associated with this phenomenon. Furthermore, bispecific antibodies were selectively generated when several anti-CCP- and RF-positive sera were mixed pairwise, indicating that factors other than the monospecific antibody titers may also contribute to the production of the natural bispecific antibodies. CONCLUSIONS/SIGNIFICANCE: We successfully identified the presence of natural bispecific antibodies. Our results suggest that these antibodies originate from anti-CCP and RF in the sera of RA patients. The natural occurrence of bispecific antibodies in human diseases may provide new insights for a better understanding of the diseases. Further investigations are needed to elucidate their precise generation mechanisms and explore their clinical significance in disease development and progression in a larger study population

Production of Native Bispecific Antibodies in Rabbits

BACKGROUND: A natural bispecific antibody, which can be produced by exchanging Fab arms of two IgG4 molecules, was first described in allergic patients receiving therapeutic injections with two distinct allergens. However, no information has been published on the production of natural bispecific antibody in animals. Even more important, establishment of an animal model is a useful approach to investigate and characterize the naturally occurring antibody. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated that a natural bispecific antibody can also be generated in New Zealand white rabbits by immunization with synthesized conjugates. These antibodies showed bispecificity to the components that were simultaneously used to immunize the animals. We observed a trend in our test animals that female rabbits exhibited stronger bispecific antibody responses than males. The bispecific antibody was monomeric and primarily belonged to immunoglobulin (Ig) G. Moreover, bispecific antibodies were demonstrated by mixing 2 purified monospecific antibodies in vivo and in vitro. CONCLUSIONS/SIGNIFICANCE: Our results extend the context of natural bispecific antibodies on the basis of bispecific IgG4, and may provide insights into the exploration of native bispecific antibodies in immunological diseases

Mite and pet allergen levels in homes of children born to allergic and nonallergic parents: the PIAMA study.

The Prevention and Incidence of Asthma and Mite Allergy (PIAMA) study is a birth cohort study that investigates the influence of allergen exposure on the development of allergy and asthma in the first several years of life. The objectives of this study were to investigate the relationship between a family history of allergy and/or asthma and exposure of newborn children to mite and pet allergen and to study the influence of different home and occupant characteristics on mite allergen exposure. Dust was sampled from the child's mattress and the parental mattress at 3 months after birth of the index child and analyzed for mite and pet allergens. Subjects were divided in groups according to history of asthma and allergy in their parents, and allergen exposure was studied in the different groups. Cat allergen exposure was significantly lower on parental mattresses in families with allergic mothers, but dog allergen exposure was not different. Mite allergen exposure was lower on parental mattresses in families with allergic mothers. Use of mite allergen-impermeable mattress covers reduced mite allergen exposure. Some other characteristics such as age of home and mattress were also found to influence mite allergen exposure. Parental mattresses in homes of allergic mothers had lower cat and mite (but not dog) allergen loadings than mattresses in homes of nonallergic parents. Paternal (as opposed to maternal) allergy seemed to have little influence