The identification of MHC class II restricted peptide epitopes is an important goal in immunological research. A number of computational tools have been developed for this purpose, but there is a ...lack of large-scale systematic evaluation of their performance. Herein, we used a comprehensive dataset consisting of more than 10,000 previously unpublished MHC-peptide binding affinities, 29 peptide/MHC crystal structures, and 664 peptides experimentally tested for CD4+ T cell responses to systematically evaluate the performances of publicly available MHC class II binding prediction tools. While in selected instances the best tools were associated with AUC values up to 0.86, in general, class II predictions did not perform as well as historically noted for class I predictions. It appears that the ability of MHC class II molecules to bind variable length peptides, which requires the correct assignment of peptide binding cores, is a critical factor limiting the performance of existing prediction tools. To improve performance, we implemented a consensus prediction approach that combines methods with top performances. We show that this consensus approach achieved best overall performance. Finally, we make the large datasets used publicly available as a benchmark to facilitate further development of MHC class II binding peptide prediction methods.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aims/hypothesis
Recent evidence suggests that oxidative stress may contribute to the pathogenesis of type 2 diabetes. The diet, and especially fruit and vegetables, contains a variety of compounds ...with antioxidant activity, which may have cumulative/synergistic antioxidant effects. The total antioxidant capacity, an index derived from dietary intake, is a single estimate of antioxidant capacity from all dietary antioxidants. The main aim of this study was to investigate the relationship between total antioxidant capacity and risk of type 2 diabetes.
Methods
Among 64,223 women (mean age 52 ± 7 years) from the French E3N-European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, 1751 women had validated type 2 diabetes during 15 years of follow-up. The total antioxidant capacity was estimated with the ferric ion-reducing antioxidant power (FRAP) method. Adjusted Cox proportional hazards regression models were used to calculate HRs and 95% CIs for the associations between total antioxidant capacity and type 2 diabetes risk, adjusted for potential confounders.
Results
In multivariable models, higher levels of total antioxidant capacity were associated with a lower risk of type 2 diabetes. Compared with women in the lowest quintile, women in the third, fourth and fifth quintiles for total antioxidant capacity had HRs of 0.74 (95% CI 0.63, 0.86), 0.70 (95% CI 0.59, 0.83) and 0.73 (95% CI 0.60, 0.89), respectively. The inverse association between total antioxidant capacity and risk of type 2 diabetes was linear up to values of 15 mmol/day, after which the effect reached a plateau.
Conclusions/interpretation
Our findings suggest that the total antioxidant capacity may play an important role in reducing the risk of type 2 diabetes in middle-aged women. More studies are warranted to better understand the biological mechanisms underlying this inverse association.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The prevalence of type 2 diabetes (T2D) is increasing worldwide. Recent studies have suggested that environmental factors, such as exposure to brominated flame retardants (BFRs), could play a role in ...the epidemic of T2D. The aim of this study was to analyze the association between the dietary exposure to BFRs (Hexabromocyclododecane (HBCD) and Polybromodiphenylether (PBDE)) and T2D risk in the E3N prospective cohort of French women.
Overall, 71,415 women followed for 19 years were included in the study. We performed Cox regression models to analyze the association between dietary exposure to BFRs and T2D risk.
Overall 71,415 women were included and 3667 (5.13%) developed a T2D during follow-up. The mean dietary exposure to HBCD and to PBDE was 0.22 ng/kg body weight (BW)/day and 1.21 ng/kg bw/day, respectively. There was a positive linear association between dietary exposure to HBCD and T2D risk starting from the 2nd quintile group (HR: 1.18; 95% CI: 1.06–1.30) to the 5th quintile group (HR: 1.47; 95% CI: 1.29–1.67) when compared to the 1st quintile group. We also found positive although non-linear associations between dietary exposure to PBDE and T2D risk, with an increased HR only for the 2nd and 4th vs. 1st quintile groups (HR: 1.12; 95% CI: 1.02–1.24, and HR: 1.20; 95% CI: 1.08–1.34, respectively).
The findings suggest an association between dietary exposure to BFRs and T2D risk, highlighting the importance of further investigating this association the long-term health effects of endocrine disruptors in the general population. Additional studies are needed to reproduce these findings in other populations and clarify the underlying biological mechanisms.
•The prevalence of type 2 diabetes (T2D) increased worldwide in the last decades•Understanding the role of brominated flame retardants (BFRs) in T2D epidemic is urgent•HBCD dietary exposure and T2D were characterized by positive and linear relationship•The relationship between PBDE and T2D was characterized by a non-linear association
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The objective of this study was to determine the relationship between maternal pre-pregnancy body mass index (BMI) and child hyperactivity-inattention symptoms (HIS) at 5 years, including preterm and ...term-born children, and to determine whether this association varied with gestational age. Maternal pre-pregnancy BMI and offspring HIS were assessed in 10,898 participants born ≥ 33 weeks of gestation from the ELFE cohort and 2646 children born between 23 and 34 weeks from the EPIPAGE 2 cohort. Reported pre-pregnancy weight (kg) and measured height (m) were collected from mothers at inclusion and used to classify BMI (kg/m
). Child HIS were evaluated using the Strengths and Difficulties Questionnaire around 5 years of age. Logistic regression estimated odds ratios (OR) of a high HIS score (≥ 90th percentile) in the ELFE cohort and generalized estimated equations were used in EPIPAGE 2 to account for non-independence of multiple births. As a negative control, paternal BMI was also considered as an exposure of interest in sensitivity analyses. Maternal pre-pregnancy obesity and overweight were associated with child HIS at 5 years in ELFE (adjusted OR aOR for obesity 1.27 1.06, 1.53; overweight aOR 1.16 1.00, 1.36) and pre-pregnancy obesity was associated with high HIS scores in preterm infants of EPIPAGE 2 (aOR 1.48 1.06, 2.08). In ELFE, the magnitude of the association increased with decreasing gestational age (interaction p = 0.02). High maternal pre-pregnancy BMI is associated with greater likelihood of high HIS scores in both at-term and preterm children at 5 years of age.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Coxiella burnetii is an obligate intracellular gram-negative bacterium that causes acute Q fever and chronic infections in humans. A killed, whole cell vaccine is efficacious, but vaccination can ...result in severe local or systemic adverse reactions. Although T cell responses are considered pivotal for vaccine derived protective immunity, the epitope targets of CD4(+) T cell responses in C. burnetii vaccination have not been elucidated. Since mapping CD4(+) epitopes in a genome with over 2,000 ORFs is resource intensive, we focused on 7 antigens that were known to be targeted by antibody responses. 117 candidate peptides were selected from these antigens based on bioinformatics predictions of binding to the murine MHC class II molecule H-2 IA(b). We screened these peptides for recognition by IFN-γ producing CD4(+) T cell in phase I C. burnetii whole cell vaccine (PI-WCV) vaccinated C57BL/6 mice and identified 8 distinct epitopes from four different proteins. The identified epitope targets account for 8% of the total vaccination induced IFN-γ producing CD4(+) T cells. Given that less than 0.4% of the antigens contained in C. burnetii were screened, this suggests that prioritizing antigens targeted by antibody responses is an efficient strategy to identify at least a subset of CD4(+) targets in large pathogens. Finally, we examined the nature of linkage between CD4(+) T cell and antibody responses in PI-WCV vaccinated mice. We found a surprisingly non-uniform pattern in the help provided by epitope specific CD4(+) T cells for antibody production, which can be specific for the epitope source antigen as well as non-specific. This suggests that a complete map of CD4(+) response targets in PI-WCV vaccinated mice will likely include antigens against which no antibody responses are made.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A balanced diet is essential to slowing the progression of chronic kidney disease (CKD) and managing the symptoms. Currently, no tool is available to easily and quickly assess energy and ...macronutrient intake in patients with non end-stage CKD. We aimed to develop and evaluate the validity and reproducibility of a new short 49-item food frequency questionnaire (SFFQ) adapted to patients with CKD.
The CKD-REIN study is a prospective cohort that enrolled 3033 patients with moderate or advanced CKD from a national sample of nephrology clinics. A sub-sample of 201 patients completed the SFFQ twice, at a one-year interval and were included in the reproducibility study. During this interval, 127 patients also completed six 24-h recalls and were included in the validity study. Main nutrient and dietary intakes were computed. Validity was evaluated by calculating crude, energy-adjusted and de-attenuated correlation coefficients (CC) between FFQ and the mean of the 24-h recall results. Bland-Altman plots were performed and cross-classification into quintiles of consumption of each nutrient and food group was computed. Reproducibility between the two SFFQs was evaluated by intraclass CC (ICC).
Regarding validity, CC ranged from 0.05 to 0.79 (unadjusted CC, median: 0.40) and 0.10 to 0.59 (de-attenuated CC, median: 0.35) for food group and nutrient intakes, respectively. Five of the most important nutrients of interest in CKD, i.e. protein, calcium, phosphorus, potassium, and sodium had de-attenuated CC of 0.46, 0.43, 0.39, 0.32, and 0.12, respectively. The median of classification into the same or adjacent quintiles was 68% and 65% for food and nutrient intakes, respectively, and ranged from 63% to 69% for the five nutrients mentioned before. Bland-Altman plots showed good agreement across the range of intakes. ICC ranged from 0.18 to 0.66 (median: 0.46).
The CKD-REIN SFFQ showed acceptable validity and reproducibility in a sample of patients with CKD, notably for CKD nutrients of importance. It can now be used in large-scale epidemiological studies to easily assess the relations between diet and CKD outcomes as well as in clinical routine. It may also serve as a basis for the development of FFQs in international CKD cohort networks.
Evidence suggests obesity during pregnancy is associated with offspring attention-deficit hyperactivity disorder. However, studies have been limited to evaluating the association at a single age with ...inadequate data on important maternal lifestyle confounders and unmeasured familial confounding. The objective of this study was to examine the association between maternal pre-pregnancy body mass index (BMI) and child hyperactivity–inattention symptoms (HIS) at 3, 5 and 8 years. Data came from the EDEN mother–child cohort. Maternal pre-pregnancy BMI status (kg/m
2
) was calculated using pre-pregnancy weight and height (self-reported by mothers or measured by midwives). HIS were assessed by parental-report on the Strengths and Difficulties Questionnaire at 3, 5 and 8 years of age and used to derive developmental trajectories of HIS (
n
= 1428). Multivariate models were adjusted for confounders including socioeconomic status, maternal lifestyle behaviours (exercise, diet, smoking, alcohol), childcare and a stimulating home environment. Paternal BMI was used as a negative control. Compared to a normal pre-pregnancy BMI, pre-pregnancy maternal obesity was positively associated with increased odds of a high HIS trajectory between 3 and 8 years old in both unadjusted and adjusted logistic regression (adjusted odds ratio aOR 1.87 95% CI 1.12, 3.12). Pre-pregnancy overweight was not significantly associated after adjustment for confounders (aOR 1.32 0.87, 2.01). Maternal pre-pregnancy obesity, but not overweight, was associated with increased likelihood of a high HIS trajectory in children from 3 to 8 years old. This association persisted despite controlling for many important maternal lifestyle factors and paternal BMI. Further research is warranted to identify possible mediators involved.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Diabetic retinopathy is a microvascular complication of diabetes that threatens all individuals with diabetes, leading to vision loss or blindness if left untreated. It is frequently associated with ...diabetic macular edema, which can occur at any point during the development of diabetic retinopathy. The key factors known to lead to its development include hyperglycemia, hypertension, and the duration of diabetes. Though the diet is important in the development of diabetes, its role in diabetic retinopathy has not been clearly identified. In this systematic review, we aimed to identify, summarize and interpret the literature on the association between the diet and dietary intakes of specific foods, nutrients, and food groups, and the risk of diabetic retinopathy. We searched PubMed and Web of Science for English-language studies evaluating the association between the dietary intake of individual foods, macro or micronutrients, dietary supplements, and dietary patterns and their association with retinopathy or macular edema. After reviewing potentially relevant abstracts and, when necessary, full texts, we identified 27 relevant studies. Identified studies investigated intakes of fruit, vegetables, fish, milk, carbohydrates, fibre, fat, protein, salt, potassium, vitamins C, D, and E, carotenoids, dietary supplements, green tea and alcohol. Studies suggest that adherence to the Mediterranean diet and high fruit, vegetable and fish intake may protect against the development of diabetic retinopathy, although the evidence is limited. Studies concerning other aspects of the diet are not in agreement. The role of the diet in the development of diabetic retinopathy is an area that warrants more attention.
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