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Dive into the research topics where Stuart E. Turvey is active.

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Featured researches published by Stuart E. Turvey.


Journal of Immunology | 2001

IL-10 Is Required for Regulatory T Cells to Mediate Tolerance to Alloantigens In Vivo

Masaki Hara; Cherry I. Kingsley; Masanori Niimi; Simon Read; Stuart E. Turvey; Andrew Bushell; Peter J. Morris; Fiona Powrie; Kathryn J. Wood

We present evidence that donor-reactive CD4+ T cells present in mice tolerant to donor alloantigens are phenotypically and functionally heterogeneous. CD4+ T cells contained within the CD45RBhigh fraction remained capable of mediating graft rejection when transferred to donor alloantigen-grafted T cell-depleted mice. In contrast, the CD45RBlow CD4+ and CD25+CD4+ populations failed to induce rejection, but rather, were able to inhibit rejection initiated by naive CD45RBhigh CD4+ T cells. Analysis of the mechanism of immunoregulation transferred by CD45RBlow CD4+ T cells in vivo revealed that it was donor Ag specific and could be inhibited by neutralizing Abs reactive with IL-10, but not IL-4. CD45RBlow CD4+ T cells from tolerant mice were also immune suppressive in vitro, as coculture of these cells with naive CD45RBhigh CD4+ T cells inhibited proliferation and Th1 cytokine production in response to donor alloantigens presented via the indirect pathway. These results demonstrate that alloantigen-specific regulatory T cells contained within the CD45RBlow CD4+ T cell population are responsible for the maintenance of tolerance to donor alloantigens in vivo and require IL-10 for functional activity.


The Journal of Allergy and Clinical Immunology | 2010

Mutations in STAT3 and diagnostic guidelines for hyper-IgE syndrome

Cristina Woellner; E. Michael Gertz; Alejandro A. Schäffer; Macarena Lagos; Mario Perro; Erik Glocker; Maria Cristina Pietrogrande; Fausto Cossu; José Luis Franco; Nuria Matamoros; Barbara Pietrucha; Edyta Heropolitańska-Pliszka; Mehdi Yeganeh; Mostafa Moin; Teresa Espanol; Stephan Ehl; Andrew R. Gennery; Mario Abinun; Anna Bręborowicz; Tim Niehues; Sara Sebnem Kilic; Anne K. Junker; Stuart E. Turvey; Alessandro Plebani; Berta Sanchez; Ben Zion Garty; Claudio Pignata; Caterina Cancrini; Jiri Litzman; Ozden Sanal

BACKGROUND The hyper-IgE syndrome (HIES) is a primary immunodeficiency characterized by infections of the lung and skin, elevated serum IgE, and involvement of the soft and bony tissues. Recently, HIES has been associated with heterozygous dominant-negative mutations in the signal transducer and activator of transcription 3 (STAT3) and severe reductions of T(H)17 cells. OBJECTIVE To determine whether there is a correlation between the genotype and the phenotype of patients with HIES and to establish diagnostic criteria to distinguish between STAT3 mutated and STAT3 wild-type patients. METHODS We collected clinical data, determined T(H)17 cell numbers, and sequenced STAT3 in 100 patients with a strong clinical suspicion of HIES and serum IgE >1000 IU/mL. We explored diagnostic criteria by using a machine-learning approach to identify which features best predict a STAT3 mutation. RESULTS In 64 patients, we identified 31 different STAT3 mutations, 18 of which were novel. These included mutations at splice sites and outside the previously implicated DNA-binding and Src homology 2 domains. A combination of 5 clinical features predicted STAT3 mutations with 85% accuracy. T(H)17 cells were profoundly reduced in patients harboring STAT3 mutations, whereas 10 of 13 patients without mutations had low (<1%) T(H)17 cells but were distinct by markedly reduced IFN-gamma-producing CD4(+)T cells. CONCLUSION We propose the following diagnostic guidelines for STAT3-deficient HIES. Possible: IgE >1000IU/mL plus a weighted score of clinical features >30 based on recurrent pneumonia, newborn rash, pathologic bone fractures, characteristic face, and high palate. Probable: These characteristics plus lack of T(H)17 cells or a family history for definitive HIES. Definitive: These characteristics plus a dominant-negative heterozygous mutation in STAT3.


Journal of Immunology | 2001

Differential Susceptibility of Heart, Skin, and Islet Allografts to T Cell-Mediated Rejection

Nick D. Jones; Stuart E. Turvey; Andre Van Maurik; Masaki Hara; Cherry I. Kingsley; Clare H. Smith; Andrew L. Mellor; Peter J. Morris; Kathryn J. Wood

Although it is widely accepted that there is a hierarchy in the susceptibility of different allografts to rejection, the mechanisms responsible are unknown. We show that the increased susceptibility of H-2Kb+ skin and islet allografts to rejection is not based on their ability to activate more H-2Kb-specific T cells in vivo; heart allografts stimulate the activation and proliferation of many more H-2Kb-specific T cells than either skin or islet allografts. Rejection of all three types of graft generate memory cells by 25 days posttransplant. These data provide evidence that neither tissue-specific Ags nor, surprisingly, the number of APCs carried in the graft dictate their susceptibility to T cell-mediated rejection and suggest that the graft microenvironment and size may play a more important role in determining the susceptibility of an allograft to rejection and resistance to tolerance induction.


PLOS ONE | 2010

Ontogeny of Toll-Like Receptor Mediated Cytokine Responses of Human Blood Mononuclear Cells

Nathan Corbett; Darren Blimkie; Kevin Ho; Bing Cai; Darren Sutherland; Arlene Kallos; Juliet Crabtree; Annie Rein-Weston; Pascal M. Lavoie; Stuart E. Turvey; Natalie Hawkins; Steven G. Self; Christopher B. Wilson; Adeline M. Hajjar; Edgardo S. Fortuno; Tobias R. Kollmann

Newborns and young infants suffer increased infectious morbidity and mortality as compared to older children and adults. Morbidity and mortality due to infection are highest during the first weeks of life, decreasing over several years. Furthermore, most vaccines are not administered around birth, but over the first few years of life. A more complete understanding of the ontogeny of the immune system over the first years of life is thus urgently needed. Here, we applied the most comprehensive analysis focused on the innate immune response following TLR stimulation over the first 2 years of life in the largest such longitudinal cohort studied to-date (35 subjects). We found that innate TLR responses (i) known to support Th17 adaptive immune responses (IL-23, IL-6) peaked around birth and declined over the following 2 years only to increase again by adulthood; (ii) potentially supporting antiviral defense (IFN-α) reached adult level function by 1 year of age; (iii) known to support Th1 type immunity (IL-12p70, IFN-γ) slowly rose from a low at birth but remained far below adult responses even at 2 years of age; (iv) inducing IL-10 production steadily declined from a high around birth to adult levels by 1 or 2 years of age, and; (v) leading to production of TNF-α or IL-1β varied by stimuli. Our data contradict the notion of a linear progression from an ‘immature’ neonatal to a ‘mature’ adult pattern, but instead indicate the existence of qualitative and quantitative age-specific changes in innate immune reactivity in response to TLR stimulation.


British Journal of Obstetrics and Gynaecology | 2016

Impact of maternal intrapartum antibiotics, method of birth and breastfeeding on gut microbiota during the first year of life: a prospective cohort study.

Meghan B. Azad; Theodore Konya; David S. Guttman; Radha Chari; Catherine J. Field; Sears; Piushkumar J. Mandhane; Stuart E. Turvey; Padmaja Subbarao; Allan B. Becker; James A. Scott; Anita L. Kozyrskyj

Dysbiosis of the infant gut microbiota may have long‐term health consequences. This study aimed to determine the impact of maternal intrapartum antibiotic prophylaxis (IAP) on infant gut microbiota, and to explore whether breastfeeding modifies these effects.


The Journal of Allergy and Clinical Immunology | 2010

Chapter 2: Innate Immunity

Stuart E. Turvey; David H. Broide

Recent years have witnessed an explosion of interest in the innate immune system. Questions about how the innate immune system senses infection and empowers a protective immune response are being answered at the molecular level. These basic science discoveries are being translated into a more complete understanding of the central role innate immunity plays in the pathogenesis of many human infectious and inflammatory diseases. It is particularly exciting that we are already seeing a return on these scientific investments with the emergence of novel therapies to harness the power of the innate immune system. In this review we explore the defining characteristics of the innate immune system, and through more detailed examples, we highlight recent breakthroughs that have advanced our understanding of the role of innate immunity in human health and disease.


Clinical & Experimental Allergy | 2015

Infant gut microbiota and food sensitization: associations in the first year of life

Meghan B. Azad; Theodore Konya; David S. Guttman; Catherine J. Field; Malcolm R. Sears; Kent T. HayGlass; Piushkumar J. Mandhane; Stuart E. Turvey; Padmaja Subbarao; Allan B. Becker; James A. Scott; Anita L. Kozyrskyj

The gut microbiota is established during infancy and plays a fundamental role in shaping host immunity. Colonization patterns may influence the development of atopic disease, but existing evidence is limited and conflicting.


Science | 2006

Islet Recovery and Reversal of Murine Type 1 Diabetes in the Absence of Any Infused Spleen Cell Contribution

Junko Nishio; Jason L. Gaglia; Stuart E. Turvey; Christopher J. Campbell; Christophe Benoist; Diane Mathis

A cure for type 1 diabetes will probably require the provision or elicitation of new pancreatic islet β cells as well as the reestablishment of immunological tolerance. A 2003 study reported achievement of both advances in the NOD mouse model by coupling injection of Freunds complete adjuvant with infusion of allogeneic spleen cells. It was concluded that the adjuvant eliminated anti-islet autoimmunity and the donor splenocytes differentiated into insulin-producing (presumably β) cells, culminating in islet regeneration. Here, we provide data indicating that the recovered islets were all of host origin, reflecting that the diabetic NOD mice actually retain substantial β cell mass, which can be rejuvenated/regenerated to reverse disease upon adjuvant-dependent dampening of autoimmunity.


The New England Journal of Medicine | 2016

Exome Sequencing and the Management of Neurometabolic Disorders

Maja Tarailo-Graovac; Casper Shyr; Colin Ross; Gabriella A. Horvath; Ramona Salvarinova; Xin C. Ye; Lin Hua Zhang; Amit P. Bhavsar; Jessica Lee; Britt I. Drögemöller; Mena Abdelsayed; Majid Alfadhel; Linlea Armstrong; Matthias R. Baumgartner; Patricie Burda; Mary B. Connolly; Jessie M. Cameron; Michelle Demos; Tammie Dewan; Janis Dionne; A. Mark Evans; Jan M. Friedman; Ian Garber; Suzanne Lewis; Jiqiang Ling; Rupasri Mandal; Andre Mattman; Margaret L. McKinnon; Aspasia Michoulas; Daniel Metzger

BACKGROUND Whole-exome sequencing has transformed gene discovery and diagnosis in rare diseases. Translation into disease-modifying treatments is challenging, particularly for intellectual developmental disorder. However, the exception is inborn errors of metabolism, since many of these disorders are responsive to therapy that targets pathophysiological features at the molecular or cellular level. METHODS To uncover the genetic basis of potentially treatable inborn errors of metabolism, we combined deep clinical phenotyping (the comprehensive characterization of the discrete components of a patients clinical and biochemical phenotype) with whole-exome sequencing analysis through a semiautomated bioinformatics pipeline in consecutively enrolled patients with intellectual developmental disorder and unexplained metabolic phenotypes. RESULTS We performed whole-exome sequencing on samples obtained from 47 probands. Of these patients, 6 were excluded, including 1 who withdrew from the study. The remaining 41 probands had been born to predominantly nonconsanguineous parents of European descent. In 37 probands, we identified variants in 2 genes newly implicated in disease, 9 candidate genes, 22 known genes with newly identified phenotypes, and 9 genes with expected phenotypes; in most of the genes, the variants were classified as either pathogenic or probably pathogenic. Complex phenotypes of patients in five families were explained by coexisting monogenic conditions. We obtained a diagnosis in 28 of 41 probands (68%) who were evaluated. A test of a targeted intervention was performed in 18 patients (44%). CONCLUSIONS Deep phenotyping and whole-exome sequencing in 41 probands with intellectual developmental disorder and unexplained metabolic abnormalities led to a diagnosis in 68%, the identification of 11 candidate genes newly implicated in neurometabolic disease, and a change in treatment beyond genetic counseling in 44%. (Funded by BC Childrens Hospital Foundation and others.).


Journal of Clinical Investigation | 2005

Noninvasive imaging of pancreatic inflammation and its reversal in type 1 diabetes

Stuart E. Turvey; Eric F. Swart; Maria C. Denis; Umar Mahmood; Christophe Benoist; Ralph Weissleder; Diane Mathis

A major stumbling block for research on and treatment of type 1 diabetes is the inability to directly, but noninvasively, visualize the lymphocytic/inflammatory lesions in the pancreatic islets. One potential approach to surmounting this impediment is to exploit MRI of magnetic nanoparticles (MNP) to visualize changes in the microvasculature that invariably accompany inflammation. MNP-MRI did indeed detect vascular leakage in association with insulitis in murine models of type 1 diabetes, permitting noninvasive visualization of the inflammatory lesions in vivo in real time. We demonstrate, in proof-of-principle experiments, that this strategy allows one to predict, within 3 days of completing treatment with an anti-CD3 monoclonal antibody, which NOD mice with recent-onset diabetes are responding to therapy and may eventually be cured. Importantly, an essentially identical MNP-MRI strategy has previously been used with great success to image lymph node metastases in prostate cancer patients. This success strongly argues for rapid translation of these preclinical observations to prediction and/or stratification of type 1 diabetes and treatment of individuals with the disease; this would provide a crucially needed early predictor of response to therapy.

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Aaron F. Hirschfeld

University of British Columbia

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