Clinical and experimental immunology
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Clin. Exp. Immunol. · Mar 2012
ReviewImmunology in clinic review series; focus on autoinflammatory diseases: role of inflammasomes in autoinflammatory syndromes.
OTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIES Allergy, Host Responses, Cancer, Type 1 diabetes and viruses, Metabolic diseases. ⋯ Autoinflammatory syndromes are disorders characterized by the hyperactivation of the innate immune system in the absence of microbial infection or autoantibody production. Some autoinflammatory syndromes are associated with recurrent episodes of fever and systemic inflammation that are caused by dysregulated activation of inflammasomes, molecular platforms responsible for the activation of caspase-1 and the production of interleukin (IL)-1β. In this review we will discuss the role of IL-1β and the inflammasomes in host defence and how mutations of two genes, NLRP3 and PYRIN, leads to the autoinflammatory syndromes, cryopyrin-associated periodic syndromes (CAPS) and familial Mediterranean fever (FMF). Both CAPS and FMF are characterized by increased inflammasome activity and overproduction of IL-1β which is ultimately responsible for disease manifestations. Importantly, understanding the molecular mechanisms of these syndromes has led to effective treatment for these rare diseases with biological drugs that target IL-1β-mediated signalling.
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Clin. Exp. Immunol. · Jan 2012
ReviewTranslational Mini-Review Series on B cell subsets in disease. Reconstitution after haematopoietic stem cell transplantation - revelation of B cell developmental pathways and lineage phenotypes.
Haematopoietic stem cell transplantation (HSCT) is an immunological treatment that has been used for more than 40 years to cure a variety of diseases. The procedure is associated with serious side effects, due to the severe impairment of the immune system induced by the treatment. ⋯ Here, we discuss the current knowledge of humoral problems and B cell development after HSCT, and relate these to the current understanding of human peripheral B cell development. We describe how these studies have aided the identification of subsets of transitional B cells and also a robust memory B cell phenotype.
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Clin. Exp. Immunol. · May 2011
Review Historical ArticleWhat does the future hold for clinical studies in vasculitis?
The era prior to 1990 was a time of careful observation of disease presentation, course, outcomes and meticulous pathology studies. These mainly single-centre studies introduced new life-saving therapies for drugs still used effectively today. In the 1970-1980s, cyclophosphamide (CyP) added to glucocorticosteroids (GCS) was shown to be life-saving. ⋯ Unmet needs and strategies are as follows: (1) to increase the numbers of vasculitis-trained physicians; (2) to define risk-benefit formulae for chronic maintenance therapy versus discontinuation of treatment after remission; (3) to define risk- and cost-benefit formulae for laboratory monitoring; (4) large-scale studies with longer follow-up that explore inhibition of interleukin-5 in CSS; (5) to explore the value of anti-interferon-γ for GCA, Takayasu's and other granulomatous vasculitides; and (6) identification of aetiological factors: cures will probably be linked to knowledge of the antigen driving the disease, plus vulnerabilities of the patient that prepare them to develop an illness phenotype. Improved outcomes using anti-inflammatory/immunosuppressive agents do not rule out infection as a driver for autoimmunity. Techniques that can facilitate pathogen discovery have never been more sophisticated.
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Clin. Exp. Immunol. · Mar 2010
ReviewPharmacogenomics: a new paradigm to personalize treatments in nephrology patients.
Although notable progress has been made in the therapeutic management of patients with chronic kidney disease in both conservative and renal replacement treatments (dialysis and transplantation), the occurrence of medication-related problems (lack of efficacy, adverse drug reactions) still represents a key clinical issue. Recent evidence suggests that adverse drug reactions are major causes of death and hospital admission in Europe and the United States. The reasons for these conditions are represented by environmental/non-genetic and genetic factors responsible for the great inter-patient variability in drugs metabolism, disposition and therapeutic targets. ⋯ Therefore, to identify multi-genetic influence on drug response, researchers and clinicians from different fields of medicine and pharmacology have started to perform pharmacogenomic studies employing innovative whole genomic high-throughput technologies. However, to date, only few pharmacogenomics reports have been published in nephrology underlying the need to enhance the number of projects and to increase the research budget for this important research field. In the future we would expect that, applying the knowledge about an individual's inherited response to drugs, nephrologists will be able to prescribe medications based on each person's genetic make-up, to monitor carefully the efficacy/toxicity of a given drug and to modify the dosage or number of medications to obtain predefined clinical outcomes.
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Clin. Exp. Immunol. · Aug 2008
ReviewTranslational mini-review series on the immunogenetics of gut disease: immunogenetics of coeliac disease.
Recent advances in immunological and genetic research in coeliac disease provide new and complementary insights into the immune response driving this chronic intestinal inflammatory disorder. Both approaches confirm the central importance of T cell-mediated immune responses to disease pathogenesis and have further begun to highlight other relevant components of the mucosal immune system, including innate immunity and the control of lymphocyte trafficking to the mucosa. ⋯ These risk regions implicate genes involved in the immune system. Overlap with autoimmune diseases is striking with several of these regions being shown to confer susceptibility to other chronic immune-mediated diseases, particularly type 1 diabetes.