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151.
Catherine Riou Elsa du Bruyn Cari Stek Remy Daroowala Rene T. Goliath Fatima Abrahams Qonita Said-Hartley Brian W. Allwood Nei-Yuan Hsiao Katalin A. Wilkinson Cecilia S. Lindestam Arlehamn Alessandro Sette Sean Wasserman Robert J. Wilkinson 《The Journal of clinical investigation》2021,131(12)
T cells are involved in control of coronavirus disease 2019 (COVID-19), but limited knowledge is available on the relationship between antigen-specific T cell response and disease severity. Here, we used flow cytometry to assess the magnitude, function, and phenotype of SARS coronavirus 2–specific (SARS-CoV-2–specific) CD4+ T cells in 95 hospitalized COVID-19 patients, 38 of them being HIV-1 and/or tuberculosis (TB) coinfected, and 38 non–COVID-19 patients. We showed that SARS-CoV-2–specific CD4+ T cell attributes, rather than magnitude, were associated with disease severity, with severe disease being characterized by poor polyfunctional potential, reduced proliferation capacity, and enhanced HLA-DR expression. Moreover, HIV-1 and TB coinfection skewed the SARS-CoV-2 T cell response. HIV-1–mediated CD4+ T cell depletion associated with suboptimal T cell and humoral immune responses to SARS-CoV-2, and a decrease in the polyfunctional capacity of SARS-CoV-2–specific CD4+ T cells was observed in COVID-19 patients with active TB. Our results also revealed that COVID-19 patients displayed reduced frequency of Mycobacterium tuberculosis–specific CD4+ T cells, with possible implications for TB disease progression. These results corroborate the important role of SARS-CoV-2–specific T cells in COVID-19 pathogenesis and support the concept of altered T cell functions in patients with severe disease. 相似文献
152.
Human leukocyte antigen (HLA) class I alleles are known to affect the cytotoxic T lymphocyte responses and influence susceptibility to viral infections. The objective of the present study was to find out whether HLA class I alleles are associated with clinical manifestations of dengue virus infection. The profile of HLA class I alleles were investigated in 224 human subjects [85 dengue fever (DF) cases, 29 dengue hemorrhagic fever (DHF) cases and 110 healthy controls (HCs)] from Western India using PCR based methods. Results revealed significantly higher frequency of HLA-A∗33 in DF cases compared to HCs [P = 0.032, Odds ratio (OR) 2.12]. The frequency of HLA-A∗02:11 was higher in DHF cases compared to DF cases. The frequency of HLA-B∗18 was significantly higher in dengue (DEN) cases [P = 0.047 Pc = 0.846, OR 3.53]. The frequency of HLA-Cw∗07 allele was significantly higher in DEN cases [DEN vs. HCs: P = 0.0120, Pc = 0.168, OR 2.00]. Significance was observed even when the cases were categorized in to DF and DHF [DF vs. HCs: P = 0.0349, Pc = 0.49, OR 1.87; DHF vs. HCs: P = 0.0399, Pc = 0.56, OR 2.4]. The combined frequency of HLA-Cw∗07 with HLA-DRB1∗07/∗15 genotype was significantly higher in DHF cases as compared to DF and HCs [DHF vs. HCs: P = 0.022, OR 5.31; DHF vs. DF: P = 0.027, OR 5.49]. On the other hand, the frequency of combination of HLA-Cw∗07 without HLA-DRB1∗07 was significantly higher in DF cases compared to HCs [DF vs. HCs: P = 0.002, OR 2.42 (1.28–4.55)]. The results suggest that HLA-A∗∗33 may be associated with DF while HLA-B∗18 and HLA-Cw∗07 alleles may be associated with symptomatic dengue requiring hospitalization. In the presence of HLA-DRB1∗07/∗15 genotype, HLA-Cw∗07 is associated with increased risk of developing DHF while in the presence of other HLA-DRB1 alleles, HLA-Cw∗07 is associated with DF. 相似文献
153.
Luca Passamonti Francesco Fera Alessandro Tessitore Antonio Russo Antonio Cerasa Cecilia M. Gioia Maria R. Monsurrò Raffaella Migliaccio Gioacchino Tedeschi Aldo Quattrone 《Neurobiology of aging》2013
Previous studies have shown that affective symptoms are part of the clinical picture in amyotrophic lateral sclerosis (ALS), the most common motor neuron disorder in elderly people. Diffuse neurodegeneration of limbic regions (e.g., prefrontal cortex [PFC], amygdala) was demonstrated in ALS post-mortem, although the mechanisms of emotional dysregulation in ALS in vivo remain unclear. Using functional imaging, we assessed the brain responses to emotional faces in 11 cognitively unimpaired ALS patients and 12 healthy controls (HCs). We tested whether regional activities and connectivity patterns in the limbic system differed between ALS patients and HCs and whether the variability in clinical measures modulated the neuroimaging data. Relative to HCs, ALS patients displayed greater activation in a series of PFC areas and altered left amygdala–PFC connectivity. Anxiety modulated the right amygdala–PFC connectivity in HCs but not in ALS patients. Reduced right premotor cortex activity and altered left amygdala–supplementary motor area connectivity were associated with longer disease duration and greater disease severity, respectively. Our findings demonstrate dysfunctions of the limbic system in ALS patients at early stages of the disease, and extend our knowledge about the interplay between emotional brain areas and the regions traditionally implicated in motor control. 相似文献
154.
155.
Roberto Ronca Patrizia Alessi Daniela Coltrini Emanuela Di Salle Arianna Giacomini Daria Leali Michela Corsini Mirella Belleri Chiara Tobia Cecilia Garlanda Elisa Bonomi Regina Tardanico William Vermi Marco Presta 《The Journal of pathology》2013,230(2):228-238
Fibroblast growth factors (FGFs) exert autocrine/paracrine functions in prostate cancer by stimulating angiogenesis and tumour growth. Here dihydrotestosterone (DHT) up‐regulates FGF2 and FGF8b production in murine TRAMP‐C2 prostate cancer cells, activating a FGF‐dependent autocrine loop of stimulation. The soluble pattern recognition receptor long pentraxin‐3 (PTX3) acts as a natural FGF antagonist that binds FGF2 and FGF8b via its N‐terminal domain. We demonstrate that recombinant PTX3 protein and the PTX3‐derived pentapeptide Ac‐ARPCA‐NH2 abolish the mitogenic response of murine TRAMP‐C2 cells and human LNCaP prostate cancer cells to DHT and FGFs. Also, PTX3 hampers the angiogenic activity of DHT‐activated TRAMP‐C2 cells on the chick embryo chorioallantoic membrane (CAM). Accordingly, human PTX3 overexpression inhibits the mitogenic activity exerted by DHT or FGFs on hPTX3_TRAMP‐C2 cell transfectants and their angiogenic activity. Also, hPTX3_TRAMP‐C2 cells show a dramatic decrease of their angiogenic and tumourigenic potential when grafted in syngeneic or immunodeficient athymic male mice. A similar inhibitory effect is observed when TRAMP‐C2 cells overexpress only the FGF‐binding N‐terminal PTX3 domain. In keeping with the anti‐tumour activity of PTX3 in experimental prostate cancer, immunohistochemical analysis of prostate needle biopsies from primary prostate adenocarcinoma patients shows that parenchymal PTX3 expression, abundant in basal cells of normal glands, is lost in high‐grade prostatic intraepithelial neoplasia and in invasive tumour areas. These results identify PTX3 as a potent FGF antagonist endowed with anti‐angiogenic and anti‐neoplastic activity in prostate cancer. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
156.
Mara Cerqueiro Bybrant Lena Grahnquist Eva Örtqvist Cecilia Andersson Gun Forsander Helena Elding Larsson 《Autoimmunity》2013,46(5):221-227
AbstractObjectives: This study explored the association between tissue transglutaminase autoantibody (tTGA), high-risk human leucocyte antigen (HLA) genotypes and islet autoantibodies in children with newly diagnosed type 1 diabetes (T1D).Patients and methods: Dried blood spots and serum samples were taken at diagnosis from children <18?years of age participating in Better Diabetes Diagnosis (BDD), a Swedish nationwide prospective cohort study of children newly diagnosed with T1D. We analyzed tTGA, high-risk HLA DQ2 and DQ8 (DQX is neither DQ2 nor DQ8) and islet auto-antibodies (GADA, IA-2A, IAA, and three variants of Zinc transporter; ZnT8W, ZnT8R, and ZnT8QA).Results: Out of 2705 children diagnosed with T1D, 85 (3.1%) had positive tTGA and 63 (2.3%) had borderline values. The prevalence of tTGA was higher in children with the HLA genotypes DQ2/2, DQ2/X or DQ2/8 compared to those with DQ8/8 or DQ8/X (p?=?.00001) and those with DQX/X (p?≤?.00001). No significant differences were found in relation to islet autoantibodies or age at diagnosis, but the presence of tTGA was more common in girls than in boys (p?=?.018).Conclusion: tTGA at T1D diagnosis (both positive and borderline values 5.4%) was higher in girls and in children homozygous for DQ2/2, followed by children heterozygous for DQ2. Only children with DQ2 and/or DQ8 had tTGA. HLA typing at the diagnosis of T1D can help to identify those without risk for CD. 相似文献
157.
Chiaravalloti Nancy D. Amato Maria Pia Brichetto Giampaolo Chataway Jeremy Dalgas Ulrik DeLuca John Meza Cecilia Moore Nancy B. Feys Peter Filippi Massimo Freeman Jennifer Inglese Matilde Motl Rob Rocca Maria Assunta Sandroff Brian M. Salter Amber Cutter Gary Feinstein Anthony 《Journal of neurology》2021,268(5):1598-1607
Journal of Neurology - Individuals with pre-existing chronic illness have shown increased anxiety and depression due to COVID-19. Here, we examine the impact of the COVID-19 pandemic on emotional... 相似文献
158.
Ravel Jean-Marie Benkirane Mehdi Calmels Nadège Marelli Cecilia Ory-Magne Fabienne Ewenczyk Claire Halleb Yosra Tison François Lecocq Claire Pische Guillaume Casenave Philippe Chaussenot Annabelle Frismand Solène Tyvaert Louise Larrieu Lise Pointaux Morgane Drouot Nathalie Bossenmeyer-Pourié Carine Oussalah Abderrahim Guéant Jean-Louis Leheup Bruno Bonnet Céline Anheim Mathieu Tranchant Christine Lambert Laëtitia Chelly Jamel Koenig Michel Renaud Mathilde 《Journal of neurology》2021,268(5):1927-1937
Journal of Neurology - STUB1 has been first associated with autosomal recessive (SCAR16, MIM# 615768) and later with dominant forms of ataxia (SCA48, MIM# 618093). Pathogenic variations in STUB1... 相似文献
159.
Thomas Klopstock MD Aleksandar Videnovic MD Almut Turid Bischoff MD Cecilia Bonnet MD Laura Cif MD Cynthia Comella MD Marta Correa-Vela MD Maria L. Escolar MD Jamie L. Fraser MD Victoria Gonzalez MD Neal Hermanowicz MD Robert Jech MD Hyder A. Jinnah MD Tomasz Kmiec MD Anthony Lang MD Maria J. Martí MD Saadet Mercimek-Andrews MD Migvis Monduy MD Graeme A.M. Nimmo MBBS Belen Perez-Dueñas MD Helle Cecilie Viekilde Pfeiffer MD Lluis Planellas MD Emmanuel Roze MD Nivedita Thakur MD Laura Tochen MD Nora Vanegas-Arroyave MD Giovanna Zorzi MD Colleen Burns PhD Feriandas Greblikas MD 《Movement disorders》2021,36(6):1342-1352
160.
Alice Morgunova Irina Pokhvisneva Saara Nolvi Sonja Entringer Pathik Wadhwa John Gilmore Martin Styner Claudia Buss Roberto Britto Sassi Geoffrey B.C. Hall Kieran J. ODonnell Michael J. Meaney Patricia P. Silveira Cecilia A. Flores 《Journal of psychiatry & neuroscience : JPN》2021,46(1):E154
BackgroundGenetic variation in the guidance cue DCC gene is linked to psychopathologies involving dysfunction in the prefrontal cortex. We created an expression-based polygenic risk score (ePRS) based on the DCC coexpression gene network in the prefrontal cortex, hypothesizing that it would be associated with individual differences in total brain volume.MethodsWe filtered single nucleotide polymorphisms (SNPs) from genes coexpressed with DCC in the prefrontal cortex obtained from an adult postmortem donors database (BrainEAC) for genes enriched in children 1.5 to 11 years old (BrainSpan). The SNPs were weighted by their effect size in predicting gene expression in the prefrontal cortex, multiplied by their allele number based on an individual’s genotype data, and then summarized into an ePRS. We evaluated associations between the DCC ePRS and total brain volume in children in 2 community-based cohorts: the Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) and University of California, Irvine (UCI) projects. For comparison, we calculated a conventional PRS based on a genome-wide association study of total brain volume.ResultsHigher ePRS was associated with higher total brain volume in children 8 to 10 years old (β = 0.212, p = 0.043; n = 88). The conventional PRS at several different thresholds did not predict total brain volume in this cohort. A replication analysis in an independent cohort of newborns from the UCI study showed an association between the ePRS and newborn total brain volume (β = 0.101, p = 0.048; n = 80). The genes included in the ePRS demonstrated high levels of coexpression throughout the lifespan and are primarily involved in regulating cellular function.LimitationsThe relatively small sample size and age differences between the main and replication cohorts were limitations.ConclusionOur findings suggest that the DCC coexpression network in the prefrontal cortex is critically involved in whole brain development during the first decade of life. Genes comprising the ePRS are involved in gene translation control and cell adhesion, and their expression in the prefrontal cortex at different stages of life provides a snapshot of their dynamic recruitment. 相似文献