HLA peptide-binding pocket diversity modulates immunological complications after cord blood transplant in acute leukaemia.

Pocket motifs and their amino acid positions of HLA molecules are known to govern antigen presentation to effector cells. Our objective was to analyse their influence on the risk of graft-versus-host disease (GVHD) and relapse after umbilical cord blood transplant (UCBT). The transplant characteristics of 849 patients with acute leukaemia were obtained from the Eurocord/EBMT database. Higher acute (a) GVHD was associated with homozygosity of UCB HLA-C amino acid positions 77 and 80 (NN/KK) (p = 0.008). Severe aGVHD was associated with HLA-A pocket B YSAVMENVHY motif (p = 0.002) and NN and RR genotypes of the HLA-C amino acid positions 77 and 156 (p = 0.006 and p = 0.002). Such risk was also increased in case of recipient and UCB mismatches in P4 (p < 0.0001) and P9 (p = 0.003) pockets of HLA-DQB1 alleles. For chronic GVHD, the pocket B YYAVMEISNY motif of the HLA-B*15:01 allele and the absence of mismatch between recipient and UCB in the P6 pocket of HLA-DRB1 were associated with a lower risk (p = 0.0007 and p = 0.0004). In relapse, both UCB pocket B YFAVMENVHY belonging to HLA-A*32:01 and recipient pocket B YDSVGENYQY motif of the HLA-C*07:01 allele were associated with higher risk (p = 0.0026 and p = 0.015). We provide clues on HLA-mediated cellular interactions and their role in the development of GVHD and relapse.

Immune cell subsets in patients with bipolar disorder or schizophrenia with history of childhood maltreatment.

A history of Childhood Maltreatment (CM) has been repeatedly associated with an increased risk of developing bipolar disorders (BD) or schizophrenia (SZ). The impact of severe stress induced by CM has been proposed to be mediated by elevated inflammation reflected by dysregulated inflammatory processes. Little is known about the potential impact of CM on lymphocyte subpopulations or the role of pre-existing infections on CM physiological consequences. This study therefore explored the role of CM and past infection exposure impact on lymphocyte subpopulations to give an indication of their relevance as stressors in the pathoetiology of major mood and psychotic disorders. 118 adult patients with SZ, and 152 with BD were included in the analysis. CM history was assessed by the Childhood Trauma Questionnaire (CTQ), with current and past psychiatric symptomatology also evaluated. Circulating immune cell subsets were analyzed using flow cytometry-based analysis. Past exposure to common infectious stigma including toxoplasma, cytomegalovirus (CMV) and Epstein-Barr virus (EBV) were measured by solid phase-enzyme microplate and ELISA immunoassays. The relationship between CM, biological phenotypes (including immune cell subsets distribution and past infectious status) and clinical phenotypes were analyzed using univariate and multivariate analyses. BD patients with, versus without, CM had higher levels of CD3+CD8+ cytotoxic T cells and CMV antibodies along with decreased levels of CD45RA+CCR7+CD8+ naïve CD8+ T cells, and a more severe clinical profile. CMV antibody levels were inversely associated with the CD3 + CD8 + lymphocyte subset level. SZ patients with, versus without, CM, showed lower levels of CD14 + monocytes and no specific clinical characteristics. The accumulation of different types of maltreatment associated with increased body mass index and CMV autoantibodies as well as decreased levels of CD14 + monocytes. In both BD and SZ, further analysis according to the type and the number of CM subtypes showed association with specific changes in lymphocyte cell subsets, clinical profile, and infectious stigma. Adults with BD or SZ exposed to CM exhibit specific immune cell subset profiles, clinical features, and stigma of past infections. In BD, our data indicate an interplay between CM and CMV infections, which may possibly contribute to premature aging and cellular senescence, both of which have previously been shown to associate with mood disorders. Longitudinal studies of CM-exposed patients are required to clarify the interactions of CM and viral infections, including as to the pathophysiological processes driving patient symptomatology.

Clinical and pharmacological correlates of caffeine consumption in subjects with schizophrenia - Data from the FACE-SZ cohort.

Caffeine is the most consumed psychoactive substance worldwide. Previous studies suggested higher caffeine consumption in subjects with schizophrenia spectrum disorders (SSD) as well as associations with symptoms, medication and medication side-effects. In a large and well-characterized sample of SSD subjects we explored the association between caffeine consumption and clinical (psychosis related, severity, general health) as well as pharmacological (antipsychotic treatment, sedation potential) variables. Eight hundred four subjects with data on their caffeine (coffee and tea) consumption successively recruited were included in this study. After controlling for potential confounders (demographic variables, smoking) only the negative dimension of psychosis was associated with the amount of caffeine ingested. Less severe negative symptoms were associated with higher caffeine consumption. The effect size of this association was small (partial correlation coefficient = -0.12) but significant.

Enhanced Photocatalytic Activity and Photoluminescence of ZnO Nano-Wires Coupled with Aluminum Nanostructures.

In this study, we fabricated a hybrid plasmonic/semiconductor material by combining the chemical bath deposition of zinc oxide nanowires (ZnONWs) with the physical vapor deposition of aluminum nanostructures (AlNSs) under controlled temperature and atmosphere. The morphological and the optical properties of the ZnONWs/AlNSs hybrid material fabricated at different temperatures (250, 350, and 450 °C) and thicknesses (5, 7, and 9 nm) of Al layers were investigated. By adjusting the deposition and annealing parameters, it was possible to tune the size distribution of the AlNSs. The resonant coupling between the plasmonic AlNSs and ZnONWs leads to an enhanced photoluminescence response. The photocatalytic activity was studied through photodegradation under UV-light irradiation of methylene blue (MB) adsorbed at the surface of ZnO. The MB photodegradation experiment reveals that the ZnONWs covered with 7 nm aluminum film and annealed at 450 °C exhibit the highest degradation efficiency. The comparison between ZnONws and ZnONws/AlNSs shows a photoluminescence enhancement factor of 1.7 and an increase in the kinetics constant of photodegradation with a factor of 4.

An Ecological Study Indicates the Importance of Ultraviolet A Protection in Sunscreens.

The use of sunscreens is recommended to limit the impact of sun exposure on the skin. The objective of this study was to examine the relationship between sunscreen sales and melanoma in 4 different countries with diverse sunscreen regulations. Data from publicly avail-able databases were examined for Sweden, England, Australia, and the USA from 1999 to 2018. The association between incidence of melanoma and sunscreen sales was estimated using a generalized estimating equation, and modelling was used to predict melanoma cases. Incidence of melanoma was positively associated with sunscreen sales in England, Australia, and the USA, and negatively associated with sunscreen sales in Sweden. Growth rates in melanoma cases of 0.42%, 16.7%, 19.1% and 12.2% were predicted for Sweden, England, Australia, and the USA, respectively. The differences observed between England, Australia, and the USA, on the one hand, and Sweden, on the other hand, are consistent with the adoption of strong regulations requiring the use of ultraviolet A blocking agents in sunscreens.

[Production of knowledge using data collected by associations of patients: The fibromyalgia example]. / Production de savoirs à partir de données collectées par les associations de malades - L'exemple de la fibromyalgie.

To respond to the social challenge of medical knowledge democratisation, numerous initiatives have been developed: information, training or consultation of patients or research applications funded by associations of patients. Only a few numbers of collaborations are initiated by the persons directly involved (patients and relatives) or fulfill association research need. We have adopted and tested such an approach with the French fibromyalgia association (Fibromyalgie France). Our work demonstrates the interest to use data collected by associations of patients to answer to their questioning or to rise further relevant research questions. Such participative approach will have a pertinent and significant impact on the knowledge of diseases and on the development of collaborative actions of research, providing a better answer to patient needs, while being methodologically rigorous.

TITLE: Production de savoirs à partir de données collectées par les associations de malades - L'exemple de la fibromyalgie. ABSTRACT: Pour répondre au défi sociétal de démocratisation de l'accès à la connaissance, différentes initiatives de recherches participatives se développent : actions d'information, de formation ou de consultation des citoyens ou par l'intermédiaire de demandes de financement par des chercheurs auprès des associations. Cependant, peu des collaborations chercheurs-malades sont à l'initiative des personnes concernées, les patients et leurs familles. Nous avons adopté et testé cette démarche à la demande et en coopération avec l'association Fibromyalgie France.

MICA-129Met/Val Polymorphism Is Associated with Early-Onset Breast Cancer Risk.

The major histocompatibility complex class I-related chain A (MICA), expressed on cell surface, plays an important role in the elimination of both virus-infected cells and tumor through the activation of the natural killer (NK) receptor NKG2D. A polymorphic change from methionine (Met) to valine (Val) at amino acid position 129 categorizes MICA alleles into strong and weak binders for the NKG2D receptor and has been found in a variety of immune-related disorders. In this study, we investigated the potential interaction between genetic polymorphism of MICA and the development of breast cancer. We recruited 192 unrelated Tunisian women affected by breast cancer and 205 controls age-matched women, all genotyped for MICA-129 Met/Val (rs 1051792). A significant association was found between the Val allele and Val/Val genotype and the risk of breast cancer (p = 0.002, OR = 1.64, 95% CI = [1.17-2.27]; p = 0.002, OR = 1.88, 95% CI = [1.24-2.87], respectively). After stratification with clinical-pathology parameters, we found that 71% of women aged lower than 40 years had a Val/Val genotype versus 49% (p = 0.014). About 72% of these patients having a family history of cancers had a Val/Val genotype (p = 0.04). These results suggest that tumor escape mechanism because of failure in order to activate NK cells by MICA-129 Val allele may play a role in individual susceptibility for breast cancer development in Tunisian women.

Cognitive deterioration among bipolar disorder patients infected by Toxoplasma gondii is correlated to interleukin 6 levels.

BACKGROUND: Cognitive deficits are present in a large majority of Bipolar Disorder (BD) patients and known to be a marker of bad prognosis. Because, these deficits encompass several domains and no specific medical treatment seems to be effective, it is important to better understand the mechanisms underlying cognitive deterioration. As Toxoplasma gondii is known to induce the synthesis of pro-inflammatory cytokines such as IL-6, we will explore here the possible role of T. gondii in the cognitive decline observed in BD. METHODS: 42 euthymic BD patients and 36 controls were assessed for episodic verbal memory using the CVLT and for working memory and verbal ability using the WAIS III. Patients and controls were also screened for seropositivity to T. gondii and evaluated for the levels of IL-6 transcripts. RESULTS: The seropositivity for T. gondii was significantly higher in BD patients as compared to controls (p=0.005). The cognitive deterioration index (DI) was higher in BD patients (p=5.10(-6)) and correlated to high IL-6 mRNA expression only among those infected by T. gondii (rho=0.43, p=0.01). Among deteriorated patients (defined by scores above 0.10 according to Weschler׳s definition), the IL-6 mRNA expression was twice greater (p=0.01). LIMITATIONS: Our results are to be interpreted with caution because of our small sample size and the cross-sectional design. CONCLUSIONS: A long-term exposure to inflammation, measured here with IL-6 mRNA expression in T. gondii infected BD may alter cognitive functioning. IL-6 could thus be a useful predictive marker of cognitive deterioration in BD and may help to design personalized treatment.

Relationship between Toxoplasma gondii infection and bipolar disorder in a French sample.

BACKGROUND: Prenatal exposure to viruses or parasites with tropism for the central nervous system is one of the risk factors for psychotic disorders. However, the relationship between past exposure to Toxoplasma gondii (T. gondii) and incidence of bipolar disorders (BD) is poorly documented across populations. METHODS: We explored the potential association between T. gondii exposure and BD in France, a country of high prevalence of Toxoplasmosis, comparing the prevalence of serological markers (IgG/IgM class antibodies) for T. gondii infection in 110 BD patients and 106 healthy controls all living in France. In a subgroup of 42 patients and 42 controls we also evaluated the levels of interleukin 6 (IL-6) transcripts, an adjunct marker of inflammation. RESULTS: We found that the sero-positive group for IgG antibodies to T. gondii had a 2.7 fold odds of having BD as compared to the sero-negative group (OR=2.17 CI 95%=1.09-4.36, p=0.028). Despite the fact that BD patients had significantly higher levels of IL-6 than the non-patient controls, no notable association between T. gondii status and IL-6 transcript levels was found. We did not find any clinical or demographic correlates of Toxoplasma exposure in the study population. LIMITATIONS: Our results are to be interpreted with caution because of our small sample size. RESULTS: We confirm the association between seropositive status to T. gondii and bipolar disorders reported in other populations and extend it to French patients. Our data strengthen the importance of early detection of T. gondii infected patients in order to propose specific and adequate treatments.