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Pulsipher M.A.,University of Utah | Chitphakdithai P.,Center for International Blood and Marrow Transplant Research | Logan B.R.,Medical College of Wisconsin | Navarro W.H.,Center for International Blood and Marrow Transplant Research | And 7 more authors.
Blood | Year: 2014

We compared serious early and late events experienced by 2726 bone marrow (BM) and 6768 peripheral blood stem cell (PBSC) donors who underwent collection of PBSC or BM between 2004 and 2009 as part of a prospective study through the National Marrow Donor Program. Standardized FDA definitions for serious adverse events (SAEs) were used, and all events were reviewed by an independent physician panel. BM donors had an increased risk for SAEs (2.38%for BMvs 0.56%for PBSC; odds ratio [OR], 4.13; P < .001), andwomen were twice as likely to experience an SAE (OR for men, 0.50; P 5 .005). Restricting the analysis to life-threatening, unexpected, or chronic/disabling events, BM donors maintained an increased risk for SAEs (0.99% for BM vs 0.31% for PBSC; OR, 3.20; P < .001). Notably, the incidence of cancer, autoimmune illness, and thrombosis after donation was similar in BMvs PBSC donors. In addition, cancer incidence in PBSC donorswas less than that reported in the general population (Surveillance, Epidemiology, and End Results Programdatabase). In conclusion, SAEs after donation are rare butmore often occurred in BM donors and women. In addition, there was no evidence of increased risk for cancer, autoimmune illness, and stroke in donors receiving granulocyte colony-stimulating factor during this period of observation. © 2014 by The American Society of Hematology.

Harrison R.J.,Imperial College London | Ettorre A.,Imperial College London | Little A.-M.,Anthony Nolan Research Institute | Khakoo S.I.,Imperial College London
Clinical and Experimental Immunology | Year: 2010

Natural killer (NK) cells are critical to the immune response to viral infections. Their functions are controlled by receptors for major histocompatibility complex (MHC) class I, including NKG2A and killer-cell immunoglobulin-like receptors (KIR). In order to evaluate the role of MHC class I receptors in the immune response to hepatitis C virus infection we have studied patients with chronic HCV infection by multi-parameter flow cytometry directly ex vivo. This has permitted evaluation of combinatorial expression of activating and inhibitory receptors on single NK cells. Individuals with chronic HCV infection had fewer CD56dim NK cells than healthy controls (4·9 ± 3·4% versus 9·0 ± 5·9%, P < 0·05). Expression levels of the inhibitory receptor NKG2A was up-regulated on NK cells from individuals with chronic hepatitis C virus (HCV) (NKG2A mean fluorescence intensity 5692 ± 2032 versus 4525 ± 1646, P < 0·05). Twelve individuals were treated with pegylated interferon and ribavirin. This resulted in a down-regulation of NKG2A expression on CD56dim NK cells. Individuals with a sustained virological response (SVR) had greater numbers of NKG2A-positive, KIR-negative NK cells than those without SVR (27·6 ± 9·6% NK cells versus 17·6 ± 5·7, P < 0·02). Our data show that NKG2A expression is dysregulated in chronic HCV infection and that NKG2A-positive NK cells are associated with a beneficial response to pegylated interferon and ribavirin therapy. © 2010 British Society for Immunology.

Prieto-Hinojosa A.,Anthony Nolan Research Institute | Knight A.,Anthony Nolan Research Institute | Compton C.,University of Edinburgh | Gleeson M.,Loughborough University | And 2 more authors.
Brain, Behavior, and Immunity | Year: 2014

Athletes undergoing intensive training schedules have chronic exposure to stress-induced hormones such as cortisol that can depress immune function. We compared the circulating levels of T cell receptor excision circles (TREC), a marker of recent thymic emigrants, as well as the levels of naïve and memory subsets in a group of elite endurance athletes and in controls. The athletes showed a reduction in absolute numbers of naïve T cells, particularly in CD4 T cells. In contrast, memory cells were increased. TREC levels in the athletes were significantly reduced compared to age-matched controls. Such changes resemble premature ageing of the T cell component of the immune system. Since thymic production of T cells naturally decline with age, these results raise the concern that prolonging high intensity exercise into the 4th decade of life may have deleterious consequences for athletes' health. © 2014 Elsevier Inc.

Robinson J.,Anthony Nolan Research Institute | Halliwell J.A.,Anthony Nolan Research Institute | McWilliam H.,European Bioinformatics Institute | Lopez R.,European Bioinformatics Institute | And 3 more authors.
Nucleic Acids Research | Year: 2013

It is 14 years since the IMGT/HLA database was first released, providing the HLA community with a searchable repository of highly curated HLA sequences. The HLA complex is located within the 6p21.3 region of human chromosome 6 and contains more than 220 genes of diverse function. Of these, 21 genes encode proteins of the immune system that are highly polymorphic. The naming of these HLA genes and alleles and their quality control is the responsibility of the World Health Organization Nomenclature Committee for Factors of the HLA System. Through the work of the HLA Informatics Group and in collaboration with the European Bioinformatics Institute, we are able to provide public access to these data through the website http://www.ebi.ac.uk/imgt/hla/. Regular updates to the website ensure that new and confirmatory sequences are dispersed to the HLA community and the wider research and clinical communities. This article describes the latest updates and additional tools added to the IMGT/HLA project. © The Author(s) 2012.

Robinson J.,Anthony Nolan Research Institute | Halliwell J.A.,Anthony Nolan Research Institute | McWilliam H.,European Bioinformatics Institute | Lopez R.,European Bioinformatics Institute | And 2 more authors.
Nucleic Acids Research | Year: 2013

The Immuno Polymorphism Database (IPD), http://www.ebi.ac.uk/ipd/ is a set of specialist databases related to the study of polymorphic genes in the immune system. The IPD project works with specialist groups or nomenclature committees who provide and curate individual sections before they are submitted to IPD for online publication. The IPD project stores all the data in a set of related databases. IPD currently consists of four databases: IPD-KIR, contains the allelic sequences of killer-cell immunoglobulin-like receptors, IPD-MHC, a database of sequences of the major histocompati-bility complex of different species; IPD-HPA, alloantigens expressed only on platelets; and IPD-ESTDAB, which provides access to the European Searchable Tumour Cell-Line Database, a cell bank of immunologically characterized melanoma cell lines. The data is currently available online from the website and FTP directory. This article describes the latest updates and additional tools added to the IPD project. © The Author(s) 2012.

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