Team players and helpers - describing professional identity among finnish physicians in a cross-sectional study.

BACKGROUND: Every physician has a unique professional identity. However, little is known about the diversity of identities among physicians. This study aimed to quantitatively assess the professional identity of physicians in Finland using descriptions of professional identity. METHODS: This study was part of a larger cross-sectional Finnish Physician 2018 Study. The target population consisted of all Finnish physicians under the age of 70 (N = 24,827) in 2018. The sample was drawn from physicians born on even numbered days (N = 11,336) using the Finnish Medical Association register. A total of 5,187 (46%) physicians responded. Professional identity was examined by 27 given characterisations using a five-point Likert scale. Multivariate logistic regression was used in assessing how place of work, graduation year and gender were associated with identity descriptions. RESULTS: The descriptions which most physicians identified with were "member of a working group/team" (82%), "helper" (82%), and "health expert" (79%); the majority reported these as describing them very or quite well. Identity descriptions such as "prescriber of medications" (68% vs. 45%), "prioritiser" (57% vs. 35%) and "someone issuing certificates" (52% vs. 32%) were more popular among junior than senior physicians. The biggest differences between the genders were found in the descriptions "provider of comfort" (62% vs. 40%) and "someone engaged in social work" (45% vs. 25%), with which women identified more frequently than men. CONCLUSIONS: Strong identification as a member of a team is an important finding in the increasingly multiprofessional world of health care. Importantly, most physicians shared several core professional identity descriptions (i.e., helper, health expert) that reflect the traditional image of an exemplary doctor.

Preterm-Born Young Women Have Weaker Hand Grip Strength Compared to Their Full-Term-Born Peers.

Prematurity has been linked to lower muscular fitness and increased morbidity across the human lifespan. Hand grip strength is widely used as a measure of muscle strength. Previous studies have shown inconsistent results regarding the role of vitamin D in hand grip strength. Here, we investigated hand grip strength and the effects of a yearlong vitamin D supplementation in healthy preterm-born young adults. We recruited 38 young adults born preterm at either ≤32 weeks' gestation or <34 weeks' gestation and weighing <1500 g, as well as 39 gender- and age-matched controls, for this study. Anthropometric measurements, hand grip strengths, and vitamin D concentrations were recorded. These investigations were repeated after a yearlong vitamin D supplementation intervention. There was a significant difference in the age- and gender-specific hand grip strength ranks between the preterm- and full-term-born young adults: 57.9% and 30.7%, respectively, were below average (p = 0.009). In the preterm-born group, the females had significantly lower hand grip strengths compared to their full-term-born peers, with a mean difference of -3.46 kg (95% CI: -6.68 to -0.247; p = 0.035). In a linear regression analysis, the preterm-born female adult height was negatively associated with hand grip strength (R2 = 0.24, F (1.43) = 13.61, p < 0.001). The vitamin D concentrations were increased after the supplementation period, with no association with hand grip strength. According to our results, preterm-born young females are at risk for lower muscle strength, independent of their current vitamin D status.

Heart Rate and Heart Rate Variability in Healthy Preterm-Born Young Adults and Association with Vitamin D: A Wearable Device Assessment.

Prematurity has been associated with impaired parasympathetic cardiac regulation later in life. Changes in heart rate (HR) and heart rate variability (HRV) may indicate a risk for future cardiac dysfunction. The putative role of Vitamin D on cardiac autonomic function in individuals born preterm (PT) remains unknown. This study involves monitoring autonomic cardiac regulation and Vitamin D concentrations in 30 PT and 16 full-term (FT) young adults in a free-living context. The PT subjects were born between 1994 and 1997 at Oulu University Hospital. The inclusion criteria were (1) being born ≤ 32 gestation weeks or (2) being born < 34 gestation weeks with a birth weight under 1500 g. Participants wore an Oura ring sleep tracer, a smart ring device, for 2 weeks to monitor cardiac autonomic function. Parameters related to autonomic cardiac regulation, lowest nighttime resting HR, and the root mean square of successive differences (RMSSD) to describe HRV were collected. PT males exhibited a tendency toward lower RMSSD (71.8 ± 22.6) compared to FT males (95.63 ± 29.0; p = 0.10). Female participants had a similar mean RMSSD in the FT and PT groups at 72.04 ± 33.2 and 74.0 ± 35.0, respectively. Serum 25-hydroxyvitamin D concentration did not correlate with cardiac autonomic function parameters. When assessing the lowest resting nighttime HRs and HRVs in a long-term, real-world context, healthy female PT young adults performed similarly to their FT peers. In contrast, the present study's results suggest that male PT young adults exhibit impaired autonomic cardiac function, potentially putting them at risk for cardiovascular disease later in adulthood.

The effects of mindfulness-based interventions in medical students: a systematic review.

The number of studies on the effects of mindfulness on healthcare professionals is increasing. The main aim of this study was to collate the quantitative results of original studies analyzing the effects of mindfulness-based interventions on a variety of outcomes in medical students. We also analyzed how the study design and characteristics of the intervention affect the results, and identified qualitative effects of mindfulness interventions. A literature search was performed in different databases in June 2020. Original articles meeting the following criteria were included: (1) at least 50% of the participants were medical students, (2) included a mindfulness intervention, (3) analyzed any outcome relating to mindfulness intervention, (4) peer-reviewed (5) written in English. Eventually, 31 articles including 24 different samples were included. Over half of the studies were RCTs. In over half of the studies, the intervention was 4- to 10-week original Mindfulness-Based Stress Reduction or Mindfulness-Based Cognitive Therapy or a modification of these. In general, satisfaction with the interventions was good. Based on a meta-analysis, after the intervention, the intervention group had statistically significantly fewer symptoms of stress and distress and had higher mindfulness than the controls. The beneficial effects persisted in follow-ups over months or years. Both long and shorter courses and courses with and without face-to-face sessions were effective. Both controlled and uncontrolled studies had statistically significant results. Qualitative results revealed potential factors behind the quantitative effects. The number of studies on mindfulness interventions in medical students has increased drastically. Mindfulness-based interventions seem to offer a good possibility to enhance medical students' well-being.

The educational paradigm shift-a phenomenographic study of medical teachers' experiences of practices.

BACKGROUND: This paper proposes a novel approach to the development of competence-oriented higher education, a national transformation aimed at harmonising and digitising undergraduate medical and dental education in Finland. METHODS: We apply phenomenography as a viable qualitative method for medical education research. To better understand medical teachers' expectations towards the change in the educational paradigm, we need to study teachers' experiences of the current practices in undergraduate medical and dental education. The phenomenographic approach facilitates solid links between research, educational development, and change. RESULTS: The phenomenographic study maps the qualitatively different ways in which medical teachers experience undergraduate medical and dental education practices. The answers reflect the changing educational paradigm in medical schools, suggesting practical implications for further development of medical and dental education and training. Core content analysis is preferred instructional scaffold for both teachers and students to prioritise the extensive medical education objectives. The change towards competence-based orientation is in progress and national co-operation accelerates its impact. CONCLUSION: There is an obvious need to enrich the content of the current curriculum with national guidelines that aim for congruence in assessment and objectives. Our results suggest an assessment application for the theoretical concepts presented and promote the competence orientation of education throughout the curricula of medical and dental undergraduate education. Moreover, our results contribute to current European discourses on competence-based approaches in higher education. Up-to-date pedagogical faculty development programmes are a key prerequisite for teacher empowerment and future orientation in teaching and learning for healthcare professions.

Myeloid-related protein 8/14 in plasma and serum in patients with new-onset juvenile idiopathic arthritis in real-world setting in a single center.

OBJECTIVE: The aim of this study was to analyze the usefulness of myeloid-related protein 8/14 (MRP8/14) in the prediction of disease course in a real-world setting for patients with new-onset juvenile idiopathic arthritis (JIA), to identify the relationship between MRP8/14 and disease activity using the physician's global assessment of disease activity (PGA), and determine whether the MRP8/14 levels measured in serum and plasma are equally useful. METHODS: In this prospective follow-up study, 87 new-onset non-systemic JIA patients were studied. Blood and synovial fluid samples were collected prior to any antirheumatic medication use. MRP8/14 was measured from serum (S-MRP8/14), plasma (P-MRP8/14), and synovial fluid samples using ELISA. RESULTS: The baseline MRP8/14 blood levels were significantly higher in patients using synthetic antirheumatic drugs than in patients with no systemic medications at 1 year after diagnosis in serum (mean 298 vs. 198 ng/ml, P < 0.001) and in plasma (mean 291 vs. 137 ng/ml, P = 0.001). MRP8/14 levels at the time of JIA diagnosis were higher in patients who started methotrexate during 1.5-year follow-up compared to those who achieved long-lasting inactive disease status without systemic medications (serum: mean 298 vs. 219 ng/ml, P = 0.006 and plasma: 296 vs. 141 ng/ml, P = 0.001). P-MRP8/14 was the most effective predictive variable for disease activity (by PGA) in linear multivariate regression model (combined to ESR, CRP, leukocytes, and neutrophils), whereas S-MRP8/14 was not significant. CONCLUSION: Blood MRP8/14 levels at baseline seem to predict disease course in new-onset JIA patients. P-MRP8/14 might be better than S-MRP8/14 when assessing disease activity at the time of JIA diagnosis.

The Effectiveness and Student Perceptions of Peer-Conducted Team-Based Learning Compared to Faculty-Led Teaching in Undergraduate Teaching.

Background: Today's professionals need to be capable of independent information retrieval, teamwork, and lifelong learning. To meet these demands, more active learning methods are needed in university teaching. Team-based learning (TBL) is a learner-centered method which enables activation of students in large classes. Objective: The aim of this study was to compare a method combining peer teaching and TBL (peer-conducted TBL; pTBL) with faculty-led seminar teaching. More precisely, students' opinions about teaching methods and immediate and long-term learning outcomes were aimed to compare. Methods: A faculty-led design was compared to a pTBL design when teaching pediatric and dermatological allergy in a seminar setting for 5th year medical students. For that purpose, students were randomly split into two learning groups. In a faculty-led seminar (n = 44 students) the instructor first lectured on each subject; then, named students from each group were asked to present clinical cases given to them beforehand and them raising questions were answered. In a pTBL group (n = 50) student's prior knowledge was first tested. Then, randomly selected, pre-prepared students took a tutors role in a seminar and presented clinical case to be solved in groups by all students. Students' performance was equally tested after both sessions and 5-6 months afterwards. Students' opinions were asked by an electronic survey. Results: In this study, pTBL was significantly preferred over faculty-led learning (mean grade 8.5 vs 6.5). Those participating in pTBL group studied pre-learning material more actively than those in faculty-led group. However, there was no difference in learning outcomes (immediate or long term) between the groups. Conclusion: Students prefer teaching method in which they are self in active role. Combining TBL and peer teaching may further increase the accumulation of non-academic skills like expertise and proficiency.

Delivery mode and the incidence of atopic sensitization and food allergy in a Finnish child population.

BACKGROUND: Caesarean section (CS) has been associated with an increased risk of subsequent atopic diseases, particularly asthma and respiratory allergies, but controversial findings have also been reported. Our aim was to clarify the association between the delivery mode and longitudinal (atopic) outcomes. METHODS: The target population was identified from the population register and comprised all children born between 2001 and 2006 and living in the province of South Karelia, Finland (N = 5564). The information on the delivery mode was available for 5552 children from the Finnish Medical Birth Register. Results of allergy tests (skin prick tests, specific IgE and open food challenges, OFCs) were collected from patient records of all healthcare units in the area. RESULTS: By 12 years of age, the cumulative incidence of atopic sensitization was 15% for those born by normal vaginal delivery (VD), 20% (adjusted RR 1.28; 95% CI 0.99-1.65) by assisted VD, 20% (adjusted RR 1.28; 95% CI 1.02-1.61) by elective CS and 20% (adjusted RR 1.24; 95% CI 0.99-1.56) by others, for example emergency CS. Among the offspring of mothers without atopic diseases, the incidence of food allergy (positive OFC) was 6% for those born by elective CS and 2% for those born by normal VD (adjusted RR 2.41; 95% CI 1.19-4.88), while the respective incidences were 5% and 6% (adjusted RR 0.82; 95% CI 0.33-2.06) among the offspring of mothers with atopic diseases. CONCLUSION: By adolescence, the cumulative incidences of atopic sensitization was highest among those born by assisted VD or CS. The incidence of food allergy was highest among those born by elective CS among the offspring of mothers without atopic diseases.

Atopic diseases of the parents predict the offspring's atopic sensitization and food allergy.

BACKGROUND: In genetic studies and selected study populations, parental atopy has been associated with atopic diseases in offspring. Our aim was to identify the association between parental atopic diseases and the offspring's atopic sensitization and food allergies, and their effect modifications due to the offspring's sex. METHODS: The study population (N = 5564) (born between 2001 and 2006) was identified from the population register and live in the province of South Karelia, Finland. Questionnaire-based information on parental atopic diseases was available for 3592 children. The results of skin prick tests, specific IgE tests, and open food challenges (OFC) were collected from patient records. RESULTS: By 12 years of age, the cumulative incidence of sensitization to food (14% vs 7%, hazard ratio 2.13; 95% CI 1.68-2.69), animal (10% vs 6%, 1.86; 1.42-2.44), and pollen allergens (12% vs 6%, 2.43; 1.85-3.19), as well as food allergies (positive OFC, 5% vs 2%, 2.28; 1.57-3.33), was higher in the offspring of parents with atopic diseases. The cumulative incidence for pollen sensitization was twofold higher for the female offspring of parents with atopic diseases than those of parents without, while it was almost threefold higher among males. The association between parental pollen allergy and the offspring's pollen sensitization was modified by sex according to additive scale estimates (RERI 1.03; 95% CI 0.13-1.91). CONCLUSION: Until adolescence, parental atopic diseases have a relatively strong association with the offspring's, particularly male offspring's, atopic sensitization, and food allergies. A pronounced association was found between parental pollen allergy and the male offspring's pollen sensitization.

Occurrence of pollen season at the end of the first trimester predicts clinical atopic diseases in the offspring: A Finnish population-based study.

OBJECTIVE: To evaluate the association between potential exposure to different pollen concentrations at the 11th fetal week and subsequent clinical atopic diseases. STUDY DESIGN AND SETTING: Parents of 1- to 4-year-old children (N = 3035) returned a questionnaire regarding physician-diagnosed atopic diseases. The children were born between 2001 and 2005 in the province of South Karelia, Finland. Results of allergy tests were collected from patient records in the area. RESULTS: The prevalence of atopic diseases with sensitisation was higher in children whose 11th fetal week occurred during pollen rather than non-pollen season: atopic eczema 6.3% vs. 4.3% (adjusted odds ratio, aOR 1.58, 95% CI 1.10─2.28), food allergy 5.7% vs. 3.9% (1.63; 1.12─2.38), respiratory allergy or asthma 3.7% vs. 2.2% (2.03; 1.24─3.33) and any atopic diseases 7.4% vs. 5.5% (1.48; 1.07─2.05), respectively. Respectively, the prevalence was higher in the children exposed to high rather than low tree pollen concentrations (>1000 vs. <10 particles/m3) at the 11th fetal week: 12.1% vs. 4.4% (3.35; 1.89─5.95), 12.1% vs. 3.9% (3.77; 2.11─6.72), 4.7% vs. 2.5% (2.95; 1.21─7.20) and 14.0% vs. 5.7% (3.15; 1.86─5.35). CONCLUSION: Coincidence of potential exposure to high tree pollen concentrations at the 11th fetal week is associated with subsequent clinical atopic diseases with sensitisation.

Diverse age-incidence patterns of atopic sensitization in an unselected Finnish population up to 12 years.

BACKGROUND: The temporal sequence in which allergic sensitization to different allergens emerges is not well characterized at the level of general population. OBJECTIVE: We describe the incidence patterns of atopic sensitization to different allergens from birth up to 12 years of age in an unselected Finnish population. METHODS: The study population comprised all children born between 2001 and 2006 identified from the nationwide population register as residents of the province of South Karelia, Finland (n = 5564). The results of allergy tests (22,380 results from skin prick tests, immunoglobulin E [IgE] antibodies, and open food challenges [OFCs], performed in 1827 children) were collected from patient records of all the health care units in the area. RESULTS: The incidence rates of positive results for food and animal allergens as well as positive OFCs for cow's milk showed prominent peaks at 5 months of age. Positive results for pollen allergens started to emerge after 1.5 years of age. The 12-year cumulative incidence of sensitization to food, animal, pollen, and any allergens was 12%, 8%, 10%, and 18%, respectively. The cumulative incidence of sensitization to house dust mites was 1% and to molds or latex less than 1%. Firstborn boys had the highest, and those who were not firstborn girls and children born in rural municipalities had the lowest early incidence of sensitization to inhalation allergens. CONCLUSION: In the unselected population, the atopic sensitization against food and animal allergens began before 6 months of age and was followed by sensitization to pollen allergens before 2 years of age. Primary prevention of sensitization to food and inhalation allergens should therefore occur in early infancy.

Very early introduction of semisolid foods in preterm infants does not increase food allergies or atopic dermatitis.

BACKGROUND: The optimal age for the introduction of solid foods for infants has long been a controversial issue. OBJECTIVE: To determine whether the early introduction of semisolid foods influences the incidence of food allergy or atopic dermatitis among preterm infants. METHODS: Retrospective data from 464 preterm infants born in Oulu University Hospital between 2008 and 2012 were analyzed. Age- and sex-matched full-term control children from the general population were identified. The primary outcome of the study was the difference in timing of the introduction of complementary feeding between preterm and full-term infants. The secondary outcomes were the incidences of food allergies and atopic dermatitis by the ages of 1 and 2 years. RESULTS: Semisolid food was introduced at the median corrected age of 1.4 months for all preterm infants, at 1.9 months for late preterm, at 0.9 months for very preterm, and at 0.1 months for extremely preterm infants. The cumulative incidence, either of food allergies or of atopic dermatitis, did not differ significantly between preterm infants and controls by the ages of 1 and 2 years. CONCLUSION: The very early introduction of complementary foods into the diet of preterm babies did not increase the incidence of food allergies or atopic dermatitis even among the most preterm infants. This finding supports the hypothesis that the gut-associated lymphoid tissue of preterm infants is ready to encounter food proteins and to begin the maturation process within 3 to 6 months of birth, regardless of gestational age.

The interplay between risk and preventive factors explains why some children develop allergies to certain foods and others show tolerance.

AIM: A number of studies have clarified the tolerance mechanisms and risk factors for food allergies. Our aim was to explore food allergy symptoms by target organs, together with the risk factors and how to prevent food allergies and induce tolerance. METHODS: We carried out a thorough review of studies on paediatric food allergies published in the last decade. RESULTS: Food allergy symptoms may affect the skin, nasal and oral mucosa, conjunctivae, gastrointestinal tract or, in severe cases, the respiratory tract and cardiovascular organs. Immunoglobulin E (IgE)-mediated symptoms appear rapidly after exposure to the offending allergen, whereas non-IgE-mediated symptoms are typically delayed. The immunological processes involved in non-IgE-mediated allergic reactions are poorly understood, but T-cell activation is probably involved. There are several factors that influence the food sensitisation process: genetic predisposition, disruption of oral tolerance development, impaired skin barriers in atopic eczema and the influence of microbiomes. CONCLUSION: The symptoms and intensity of reactions vary considerably with regard to food allergies, and these depend on the individual's concomitant immunological and regulatory mechanisms. There is strong evidence that dietary diversity is important for children, even when they come from families with high allergy risks.

Wheat oral immunotherapy was moderately successful but was associated with very frequent adverse events in children aged 6-18 years.

AIM: This study investigated oral immunotherapy (OIT) for children aged 6-18 years with wheat allergies. METHODS: Well-cooked wheat spaghetti was given to 100 children with wheat allergies every day for 17 weeks, increasing from 0.3 to 2000 mg of wheat protein, followed by three- and nine-month maintenance phases. Blood samples were taken before therapy and at follow-up visits. The study was carried out in 2009-2015 in four Finnish paediatric allergology units. RESULTS: The children (67% male) had a mean age of 11.6 years (range 6.1-18.6), and 57 were using wheat daily 16 months after the initiation of therapy. Allergic symptoms occurred in 94/100 children: mild in 34, moderate in 36 and severe in 24. Specific immunoglobulin E (IgE) for ω-5-gliadin was significantly higher in patients who did not reach the target dose and were related to the intensity of reactions. CONCLUSION: The majority (57%) of children with wheat allergies could use wheat in their daily diet 16 months after the initiation of OIT, but 94/100 had adverse reactions and 60 were moderate or severe. Specific IgE to ω-5-gliadin may provide a biomarker for how much wheat can be tolerated and the intensity of the reactions to immunotherapy.

FOXP3+ T cells are present in kidney biopsy samples in children with tubulointerstitial nephritis and uveitis syndrome.

BACKGROUND: Tubulointerstitial nephritis (TIN) is an inflammatory disease of unknown pathogenesis. To evaluate a possible role of regulatory T cells (Tregs) in the pathophysiology of TIN with (TINU) and without uveitis, we investigated the presence and quantity of FOXP3+ T regulatory lymphocytes in diagnostic kidney biopsies from pediatric patients. METHODS: A total of 33 patients (14 TIN and 19 TINU) were enrolled. The quantity of CD4+, FOXP3+ and double-positive T cells in formalin-fixed kidney biopsies was determined using double label immunohistochemistry with anti-human CD4 and FOXP3 antibodies. RESULTS: FOXP3 staining was successful in all 33 patients. In patients with chronic uveitis, the density of FOXP3+ cells was significantly lower (p = 0.046) than in TIN patients without uveitis or with uveitis lasting <3 months. CD4+ staining was successful in 23 patients. The density of all lymphocytes (CD4+, CD4+FOXP3+ and FOXP3+ cells) was significantly lower (p = 0.023) in patients with chronic uveitis than in other patients. CONCLUSIONS: FOXP3+ T cells are present in kidney biopsy samples from TIN and TINU patients. In patients with chronic uveitis, the density of FOXP3+ T cells is significantly lower than in other patients, suggesting a different pathomechanism for these clinical conditions.

Damaging heterozygous mutations in NFKB1 lead to diverse immunologic phenotypes.

BACKGROUND: The nuclear factor κ light-chain enhancer of activated B cells (NF-κB) signaling pathway is a key regulator of immune responses. Accordingly, mutations in several NF-κB pathway genes cause immunodeficiency. OBJECTIVE: We sought to identify the cause of disease in 3 unrelated Finnish kindreds with variable symptoms of immunodeficiency and autoinflammation. METHODS: We applied genetic linkage analysis and next-generation sequencing and functional analyses of NFKB1 and its mutated alleles. RESULTS: In all affected subjects we detected novel heterozygous variants in NFKB1, encoding for p50/p105. Symptoms in variant carriers differed depending on the mutation. Patients harboring a p.I553M variant presented with antibody deficiency, infection susceptibility, and multiorgan autoimmunity. Patients with a p.H67R substitution had antibody deficiency and experienced autoinflammatory episodes, including aphthae, gastrointestinal disease, febrile attacks, and small-vessel vasculitis characteristic of Behçet disease. Patients with a p.R157X stop-gain experienced hyperinflammatory responses to surgery and showed enhanced inflammasome activation. In functional analyses the p.R157X variant caused proteasome-dependent degradation of both the truncated and wild-type proteins, leading to a dramatic loss of p50/p105. The p.H67R variant reduced nuclear entry of p50 and showed decreased transcriptional activity in luciferase reporter assays. The p.I553M mutation in turn showed no change in p50 function but exhibited reduced p105 phosphorylation and stability. Affinity purification mass spectrometry also demonstrated that both missense variants led to altered protein-protein interactions. CONCLUSION: Our findings broaden the scope of phenotypes caused by mutations in NFKB1 and suggest that a subset of autoinflammatory diseases, such as Behçet disease, can be caused by rare monogenic variants in genes of the NF-κB pathway.

Expression of Glucocorticoid Receptors GRα and GRß in Bullous Pemphigoid.

First-line treatments of bullous pemphigoid (BP) are topical and systemic glucocorticoids (GC). The actions of GC are mediated by glucocorticoid receptors (GR), which exist in several isoforms, of which GRα and GRß are the most important. In many inflammatory diseases, up-regulation of GRß is associated with GC insensitivity. The aims of this study were to determine the expression of GRα and GRß in patients with BP and to investigate the effect of prednisolone treatment on the expression of GR isoforms in BP. Quantitative real-time PCR (qPCR) analysis demonstrated that GR isoform mRNAs are expressed in peripheral blood mononuclear cells (PBMC) from patients with BP. Expression of GRα and GRß protein was confirmed by immunohistochemical staining of BP skin biopsies and by Western blot analysis and flow cytometric analysis of PBMCs. During prednisolone treatment, GRα and GRß expression varied markedly, but changes were not suitable as a clinical marker of GC sensitivity in patients with BP.

CD4⁺ T-cell proliferation responses to wheat polypeptide stimulation in children at different stages of type 1 diabetes autoimmunity.

AIMS: Our aim was to study whether immune responses to wheat-based proteins are related to the development of type 1 diabetes. METHODS: We analysed proliferative T-cell responses after in vitro gliadin, gluten, whole wheat, and tetanus toxoid stimulation with a carboxyfluorescein succinimidyl ester (CFSE) based T-cell proliferation assay in children at various phases of type 1 diabetes autoimmunity and in healthy autoantibody-negative control children. RESULTS: At an early stage of beta cell autoimmunity the strength and frequencies of positive proliferation responses to gliadin, gluten, and whole wheat did not differ between newly seroconverted children positive for one islet autoantibody and the controls. However, in prediabetic children with at least two islet autoantibodies and also in children with newly diagnosed type 1 diabetes positive T-cell responses to gliadin were significantly less frequent and the strength of gliadin responses was reduced when compared to the controls. No differences were seen in T-cell responses to wheat-based antigens when comparing children with long-lasting type 1 diabetes with healthy controls. CONCLUSIONS/INTERPRETATION: Decreased in vitro T-cell responses to wheat-based antigens were observed in children with multiple islet autoantibodies and in those with newly diagnosed type 1 diabetes, probably reflecting a generally aberrant immune response during the development of type 1 diabetes.

Autoimmunity, hypogammaglobulinemia, lymphoproliferation, and mycobacterial disease in patients with activating mutations in STAT3.

The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of immunodysregulation polyendocrinopathy enteropathy X-linked-like syndrome. Here, we immunologically characterized 3 patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T, and p.K658N, respectively). The patients displayed multiorgan autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B-cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4(-)CD8(-)) T cells, and decreased natural killer, T helper 17, and regulatory T-cell numbers. Notably, the patient harboring the K392R mutation developed T-cell large granular lymphocytic leukemia at age 14 years. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.

[Food hyposensitization--new approach and treatment for food allergies]. / Ruokasiedätys--uusi ajattelutapa ja hoito ruoka-aineallergioihin.

Although most infants will recover from food allergy within the early years of life, at least one fifth will carry on with the disease until school age. Recent studies have managed to develop increased tolerance in children with food allergy by food hyposensitization with slowly increasing orally administered doses. In these studies either complete or partial increase of food tolerance for 80% of subjects has been achieved. The clinical results seem promising, and immunologic changes upon food hyposensitization look similar to those observed with other hyposensitization therapies.