IntroductionSeptic shock remains a major health care problem worldwide. Sepsis-induced immune alterations are thought to play a major role in patients' mortality and susceptibility to nosocomial infections. Programmed death-1 (PD-1) receptor system constitutes a newly described immunoregulatory pathway that negatively controls immune responses. It has recently been shown that PD-1 knock-out mice exhibited a lower mortality in response to experimental sepsis. The objective of the present study was to investigate PD-1-related molecule expressions in septic shock patients.MethodsThis prospective and observational study included 64 septic shock patients, 13 trauma patients and 49 healthy individuals. PD-1-related-molecule expressions were measured by flow cytometry on circulating leukocytes. Plasmatic interleukin (IL)-10 concentration as well as ex vivo mitogen-induced lymphocyte proliferation were assessed.ResultsWe observed that septic shock patients displayed increased PD-1, PD-Ligand1 (PD-L1) and PD-L2 monocyte expressions and enhanced PD-1 and PD-L1 CD4+ T lymphocyte expressions at day 1-2 and 3-5 after the onset of shock in comparison with patients with trauma and healthy volunteers. Importantly, increased expressions were associated with increased occurrence of secondary nosocomial infections and mortality after septic shock as well as with decreased mitogen-induced lymphocyte proliferation and increased circulating IL-10 concentration.ConclusionsThese findings indicate that PD-1-related molecules may constitute a novel immunoregulatory system involved in sepsis-induced immune alterations. Results should be confirmed in a larger cohort of patients. This may offer innovative therapeutic perspectives on the treatment of this hitherto deadly disease.
Killer cell immunoglobulin-like receptors (KIRs) belong to a diverse family of natural killer (NK) cell receptors recognizing human leukocyte antigen (HLA) class I molecules. Due to this functional link, KIR molecules are expected to display a high polymorphism, such as their HLA ligands. Moreover, many studies conducted in mouse and human models have shown that NK-KIR receptors play an important role in haematopoietic stem cell transplantation (HSCT). A beneficial impact of peculiar KIR ligand (HLA) mismatching has been reported suggesting a role to this combinatory HLA-KIR polymorphism. It is thus important to investigate KIR diversity in various human populations. To this end, we used polymerase chain reaction-sequence-specific primers to evaluate KIR gene in five selected populations (France, Guadeloupe, Senegal, Finland and Réunion). Genotypic and haplotypic frequencies were computed, as well as genetic distances and dendrogram (phylip package). These data illustrate the genetic relationship of these five populations through the KIR polymorphism. Results revealed a wide diversity in KIR gene frequencies in Guadeloupe and Réunion, and a high specificity in Senegal. The obtained dendrogram indicated small genetic distances between France, Guadeloupe and Réunion as well as between France and Finland. Senegal showed a distant genetic relationship with the other countries and, interestingly, an inverted ratio of coding/non-coding (KIR2DS4/1D) alleles compared with Caucasians. These data expose the broad diversity in KIR genes worldwide and show that KIR genes are pertinent tools in human population genetics. If the role of KIR donor-recipient incompatibilities is confirmed, KIR diversity according to ethnicity should be taken into account during the selection of HSCT donors.
BackgroundThe great majority of mental disorders begin during adolescence or early adulthood, although they are often detected and treated later in life. To compare mental health status of college students and their non-college-attending peers whether working, attending a secondary school, or non-college-attending peers who are neither employed nor students or trainees (NENST) will allow to focus on high risk group.MethodsData were drawn from a large cross-sectional survey conducted by phone in 2005 in four French regions in a randomly selected sample of 22,138 adults. Analyses were restricted to the college-age subsample, defined as those aged 18 to 24 (n = 2424). Sociodemographic, educational, and occupational status were determined. In addition, respondents were administered standardized instruments to assess mental health and well-being (CIDI-SF, SF-36, Sheehan Disability Scale, CAGE), mastery, social support, and isolation. The four occupational groups were compared. All analyses were stratified by gender.ResultsMental health disorders were more prevalent among the NENST group, with significant differences among men for anxiety disorders including phobias, post-traumatic stress disorder (PTSD) and panic disorder, impairing at least one role in their daily life. This was also true among women except for panic disorder. The NENST group also reported the lowest level of mastery and social support for both genders and the highest level of social isolation for women only. After adjustment, occupational status remained an independent correlate of PTSD (OR = 2.92 95 % CI = 1.4–6.1), agoraphobia (OR = 1.86 95 % CI 1.07–3.22) and alcohol dependence (OR = 2.1 95 % CI = 1.03–4.16).ConclusionCompared with their peers at work or in education/training, the prevalence of certain common mental health disorders was higher among college-aged individuals in the NENST group. Efforts should be made to help young adults in the transition between school or academic contexts and joining the workforce. It is also important to help youths with psychiatric disorders find an occupational activity and provide them information, care, support and counseling, particularly in times of economic hardship. Schools and universities may be adequate institutional settings to set health promotion programs in mental health and well-being.
cancérologie, UMR892, UFR Médecine et Techniques médicales, Nantes, France NK-cell function is regulated by a balance between inhibitory and activating killer cell immunoglobulin-like receptors (KIR) that specifically recognize HLA class I molecules. Using KIR-specific mAb to discriminate between KIR2DS1 and KIR2DL1 receptors, we show that KIR2DS1 + NK cells are C2-alloreactive only from C2 À individuals. Moreover, using an in vitro model of NK-cell expansion, we show here that the frequency of KIR2DL1 + NK cells is significantly higher in the absence of C2 ligand on stimulator EBV-B cells than in its presence. This observation was made regardless of the presence or absence of the autologous C2 ligand, suggesting that the C2 À EBV-B stimulator cells used in this in vitro model could activate unlicensed KIR2DL1 + NK cells. In the case of KIR2DL1 + /S1 + genotyped individuals, KIR2DS1 + NK-cell frequency was increased after stimulation with C2 + compared with C2 À stimulator B cells, but only from C2 À individuals. Altogether, these data highlight the C2 alloreactivity of KIR2DS1 + NK cells that is only observed in C2 À individuals. These results provide new insights into the way in which NK KIR cell expansion might be regulated in an allogeneic environment.
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