Clinical and experimental immunology
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Clin. Exp. Immunol. · Oct 2012
Randomized Controlled TrialDifferential effects of infliximab on absolute circulating blood leucocyte counts of innate immune cells in early and late rheumatoid arthritis patients.
Anti-tumour necrosis factor (TNF) biologics have revolutionized therapy of rheumatoid arthritis (RA). We compared the effects of infliximab on numbers of circulating leucocyte subsets in early RA (disease/symptom duration of ≤1 year) and late RA patients (>1 year). A control group consisted of early RA patients treated with a combination of methotrexate (MTX) and methylprednisolone. ⋯ CD16(+) granulocytes, NK cells and CD14(dim) monocytes all expressed higher levels of mTNF in RA patients. In summary infliximab is associated with decreased CD16(+) granulocyte and NK cell counts, possibly through binding of mTNF. Differential effects of infliximab between early and late RA suggest that pathogenic mechanisms change as disease progresses.
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Clin. Exp. Immunol. · Sep 2012
ReviewIs interferon-gamma the right marker for bacille Calmette-Guérin-induced immune protection? The missing link in our understanding of tuberculosis immunology.
Bacille Calmette-Guérin (BCG), developed a century ago, is the only licensed tuberculosis (TB) vaccine in use to date. The protective efficacy of BCG against TB varies with no apparent protection in some population, and mechanisms of its immune protection is poorly known, and yet BCG is the most widely used vaccine, with more than 4 billion BCG-vaccinated children globally. BCG is probably the only licensed vaccine currently in use believed to mediate immune protection through the production of interferon (IFN)-γ by CD4 T cells, which in turn activates macrophages to kill Mycobacterium tuberculosis (Mtb). ⋯ These studies point to the fact that there is a missing link in our understanding of TB immunology. Conversely, there is emerging evidence that other T cell subsets (gammadelta, γδ), CD8(+) T cells and natural killer (NK) cells may play a vital role in immune protection against Mtb infection and BCG-induced immune protection. γδ T cells and NK cells, which were considered to be part of the innate immunity in the past, have been shown to develop immunological memory upon re-encounter with the same pathogen. In this paper, the controversy over the role of IFN-γ as a marker for protective immunity against TB, and emerging data on the role of γδ T cells, CD8(+) and NK cells in TB immunology, will be presented.
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Clin. Exp. Immunol. · Apr 2012
Sevoflurane reduces severity of acute lung injury possibly by impairing formation of alveolar oedema.
Pulmonary oedema is a hallmark of acute lung injury (ALI), consisting of various degrees of water and proteins. Physiologically, sodium enters through apical sodium channels (ENaC) and is extruded basolaterally by a sodium-potassium-adenosine-triphosphatase pump (Na(+) /K(+) -ATPase). Water follows to maintain iso-osmolar conditions and to keep alveoli dry. ⋯ The wet/dry ratio in sevoflurane/LPS was reduced by 21·6% ± 2·3% in comparison to propofol/LPS-treated animals. Sevoflurane has a stimulating effect on ENaC and Na(+) /K(+) -ATPase in vitro in LPS-injured AECII. In-vivo experiments, however, give strong evidence that sevoflurane does not affect water reabsorption and oedema resolution, but possibly oedema formation.
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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. · Mar 2012
Alterations of coagulation and fibrinolysis in patients with angioedema due to C1-inhibitor deficiency.
Patients with functional deficiency of C1-inhibitor (C1-INH) suffer from recurrent acute attacks (AA) of localized oedema associated with activation of the contact system, complement and fibrinolysis. To unravel further the role of coagulation and fibrinolysis in the pathophysiology of C1-INH deficiency, we performed simultaneous thrombin and plasmin generation measurements in plasma from patients with hereditary angioedema (HAE) due to C1-INH deficiency during AA (n = 23), in remission (R) (n = 20) and in controls (n = 20). During AA thrombin generation after in-vitro activation of plasma was higher than in controls, as demonstrated by shorter thrombin peak-time (P < 0·05), higher thrombin peak-height (P < 0·001) and increased area under the curve (AUC) (P < 0·05). ⋯ This apparent discrepancy can be reconciled by elevated soluble thrombomodulin (sTM) (P < 0·01) and thrombin activatable fibrinolysis inhibitor (TAFI) in patients during AA providing possible evidence for a regulatory effect on fibrinolysis. Plasminogen activator inhibitor-1 (PAI-1) was reduced in patients during AA indicating, together with the observed reduction of plasmin generation, the consumption of fibrinolytic factors. In conclusion, our results support the involvement of coagulation and fibrinolysis in the pathophysiology of HAE and show the possible application of simultaneous measurement of thrombin and plasmin generation to evaluate different clinical conditions in HAE patients.