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81.
Gaëlle Dzangué-Tchoupou Kuberaka Mariampillai Loïs Bolko Damien Amelin Wladimir Mauhin Aurélien Corneau Catherine Blanc Yves Allenbach Olivier Benveniste 《Autoimmunity reviews》2019,18(4):325-333
Background
Myositis is a heterogeneous group of muscular auto-immune diseases with clinical and pathological criteria that allow the classification of patients into different sub-groups. Inclusion body myositis is the most frequent myositis above fifty years of age. Diagnosing inclusion body myositis requires expertise and is challenging. Little is known concerning the pathogenic mechanisms of this disease in which conventional suppressive-immune therapies are inefficacious.Objectives
Our aim was to deepen our understanding of the immune mechanisms involved in inclusion body myositis and identify specific biomarkers.Methods
Using a panel of thirty-six markers and mass cytometry, we performed deep immune profiling of peripheral blood cells from inclusion body myositis patients and healthy donors, divided into two cohorts: test and validation cohorts. Potential biomarkers were compared to myositis controls (anti-Jo1-, anti-3-hydroxyl-3-methylglutaryl CoA reductase-, and anti-signal recognition particle-positive patients).Results
Unsupervised analyses revealed substantial changes only within CD8+ cells. We observed an increase in the frequency of CD8+ cells that expressed high levels of T-bet, and containing mainly both effector and terminally differentiated memory cells. The senescent marker CD57 was overexpressed in CD8+T-bet+ cells of inclusion body myositis patients. As expected, senescent CD8+T-bet+ CD57+ cells of both patients and healthy donors were CD28nullCD27nullCD127null. Surprisingly, non-senescent CD8+T-bet+ CD57- cells in inclusion body myositis patients expressed lower levels of CD28, CD27, and CD127, and expressed higher levels of CD38 and HLA-DR compared to healthy donors. Using classification and regression trees alongside receiver operating characteristics curves, we identified and validated a frequency of CD8+T-bet+ cells >51.5% as a diagnostic biomarker specific to inclusion body myositis, compared to myositis control patients, with a sensitivity of 94.4%, a specificity of 88.5%, and an area under the curve of 0.97.Conclusion
Using a panel of thirty-six markers by mass cytometry, we identify an activated cell population (CD8+T-bet+ CD57- CD28lowCD27lowCD127low CD38+ HLA-DR+) which could play a role in the physiopathology of inclusion body myositis, and identify CD8+T-bet+ cells as a predominant biomarker of this disease. 相似文献82.
Sara Boulaïch Annie Daszuta Michel Geffard Olivier Bosler 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1994,101(3):353-364
We have previously reported that a cell suspension from the rostral part of the embryonic raphe grafted to the basal hypothalamus of 5,7-dihydroxytryptamine-denervated rats produced incomplete serotonin (5-HT) re-innervation of the suprachiasmatic nucleus (SCN) as opposed to hyper-innervation of the supraoptic nucleus (SON). We took advantage of this experimental model to investigate whether the graft-derived, 5-HT fibres retained normal ultrastructural features, and, particularly, a normal density of synaptic junctions, irrespective of the extent of target re-innervation. The intrinsic features of immunostained, graft-derived 5-HT axonal varicosities in both the SCN (ventral portion) and the SON were essentially similar to those exhibited by the respective endogenous innervation. Analysis of well-preserved varicosities in uninterrupted series of thin sections allowed us to evaluate directly the proportions of junctional to non-junctional 5-HT varicosities in both regions. Synaptic incidences were also remarkably conserved after grafting (45.5% in the SCN versus 38.5% in the SON; 48% and 38% in normal rats, respectively). Synapses were primarily reestablished on dendritic shafts, which also were identified as the major post-synaptic targets of the normal 5-HT innervations. We noted, however, a tendency toward increased numbers of symmetrical versus asymmetrical synapses in both the SCN and SON of grafted rats. Thus, irrespective of whether hypo-or hyper-innervation patterns developed post-grafting, the transplanted 5-HT neurons essentially retained normal ultrastructural features in their target territories, with a normal incidence of synaptic junctions. The data provide further support to the hypothesis that the innervation territory is the major determinant of the frequency with which ingrowing 5-HT fibres make synaptic junctions. 相似文献
83.
Defective functional response to membrane stimuli in lymphocytes from patients with benign prostatic hyperplasia.
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M Prez-Blas B Martínez-Martín J Carballido J Hontoria L I Salazar C Olivier M Alvarez-Mon 《Clinical and experimental immunology》1995,101(3):521-526
Benign prostatic hyperplasia (BPH) is a local disturbance in the prostate that may involve an inflammatory infiltrate predominantly composed of activated lymphocytes and macrophages. The activation and proliferative response of T lymphocytes to different mitogenic signals has been analysed in peripheral blood mononuclear cells (PBMC) from 45 patients with BPH and 55 healthy controls. The PBMC obtained from the patients showed a significant specific impairment in proliferation, CD25 expression and IL-2 production in response to stimulation with lectins (phytohaemagglutinin (PHA), concanavalin A (Con A)), that was not corrected by the addition of IL-2 or of phorbol esters (phorbol myristate acetate (PMA)). Also, the CD28 response was defective in patient PBMC. Activation with anti-CD3 or anti-CD2 MoAbs was normal, but the addition of PMA to these stimuli provoked a significant defective response. Only the use of transmembrane stimuli (PMA and ionomycin) elicited responses similar to those found in the control group. The results indicate that peripheral T lymphocytes from BPH patients show a functional impairment that is mainly explained by an alteration of membrane signals (PHA, CD28) and is distal to protein kinase C (PKC) activation. 相似文献
84.
85.
Philippe Hup Cline Rouveirol Isabel Brito Pierre Neuvial Philippe La Rosa Eric Viara Nicolas Stransky Gaëlle Pierron Elodie Mani Caroline Brennetot Isabelle Jannoueix Nadge Gruel Alain Aurias Olivier Delattre Franois Radvanyi Emmanuel Barillot 《European journal of medical genetics》2005,48(4):467-468
86.
Toussaint O Remacle J Dierick JF Pascal T Frippiat C Royer V Chainiaux F 《Mechanisms of ageing and development》2002,123(8):937-946
87.
Dien Pham Huy Monique Roch-Arveiller Monique Lenoir Olivier Muntaner Alain Thuret Jean-Paul Giroud 《Inflammation research》1986,18(3-4):366-371
The effect of piroxicam on rat polymorphonuclear leucocytes (PMN) has been studiedin vitro andin vivo after the induction of two acute, non specific inflammatory reactions (pleurisies induced by calcium pyrophosphate crystals (CaPP) or isologous serum).An inhibition of chemotaxis by piroxicam has been demonstrated by two techniques, the filter and agarose assaysin vivo andin vitro. An inhibition of random cell migration has been observed only at the higher drug concentration using agarose assay with CaPP-elicited cells.Piroxicam also inhibited superoxide anion generation and O2 consumption of CaPP- and serum-elicited cells.These findings suggest that piroxicam may have a direct effect on PMN responses and that this activity could, at least in part, contribute to its anti-inflammatory properties. 相似文献
88.
Cytosine methylation was studied at the level of the euchromatin/heterochromatin transition genomic region of the Arabidopsis chromosome 5 left arm. It has been shown using a monoclonal antibody against 5-methylcytosines that the density of DNA methylation
increases from the euchromatin towards the heterochromatin. YACs mapped along this region were characterized for their repeated
sequences content. Some of them, corresponding to euchromatin, euchromatin/heterochromatin border and heterochromatin regions,
were used as probes for a Southern blot analysis of methylation. This revealed that the degree of mCmCGG and GATmC methylation
increases significantly from the euchromatin towards the heterochromatin. Moreover, an analysis of cytosine methylation levels
(% of 5-methylcytosine) of different DNA fragments, inside the same genomic region, was performed using PCR and/or Southern
blot approaches. There is a gradual increase of methylation along the genomic region analyzed: CpG methylation in the euchromatic
fraction, CpG and CpNpG methylation at the euchromatin/heterochromatin transition and an additional asymmetrical methylation
in the repeated-heterochromatic fraction. The most methylated repeated family at CpG, CpNpG and asymmetrical sites is the
5S ribosomal DNA, highly methylated even though it is transcribed.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
89.
90.
El Benna J Hayem G Dang PM Fay M Chollet-Martin S Elbim C Meyer O Gougerot-Pocidalo MA 《Inflammation》2002,26(6):273-278
Superoxide anion (O2°-)production by neutrophil NADPH oxidase participates in arthritic joint lesion formation. Proinflammatory cytokines such as tumor necrosis factor (TNF), interleukin 8 (IL-8) and granulocyte/macrophage-colony stimulating factor (GM-CSF) have a priming effect on neutrophil NADPH oxidase activity. NADPH oxidase activation is dependent on phosphorylation of p47phox, a cytosolic component of the enzyme. We studied O2°-production and p47phox phosphorylation in synovial fluid (SF) from patients with rheumatoid arthritis (RA) and spondylarthropathy (SpA) according to TNF, IL-8 and GM-CSF levels. O2°-production by neutrophils isolated from SF of all the arthritis patients (RA and SpA) was higher than that of circulating resting neutrophils and when stimulated with fMLP or PMA. In addition, p47phox was partially phosphorylated in SF neutrophils compared to circulating neutrophils. High levels of TNF and IL-8 (but not GM-CSF) are detected in patient's SF (compared to circulating blood levels). TNF levels were significantly higher in RA than in SpA SF. These results suggest that increased NADPH oxidase activity could be involved in arthritic joint inflammation through increased p47phox phosphorylation. This could be the result of the presence of high levels of priming agents such as TNF and IL-8 but not GM-CSF. 相似文献