Quantification of IFNγ- and IL17-producing cells after stimulation with citrullinated proteins in healthy subjects and RA patients

Antibodies against citrullinated proteins are highly specific for rheumatoid arthritis (RA) and are currently used as a diagnostic marker. In this study, we wanted to quantify the numbers of T cells that react to a wide range of citrullinated proteins in a wide range of HLA-DR subtypes in order to investigate whether citrullination might create T-cell neo-epitopes and could initiate a universal T-cell response. Therefore, PBMCs from healthy volunteers and RA patients were stimulated with a citrullinated and non-citrullinated cell extract on IFN gamma-ELISpot. We found a significantly higher number of IFN gamma-secreting cells after stimulation with citrullinated proteins compared to non-citrullinated proteins in RA patients (1:14,441 cells vs. 1:32,880 cells) as well as in healthy subjects (1:6,261 reactive cells compared to 1:16,212 cells). Additionally, a higher number of IL17-secreting cells were found after stimulation with citrullinated proteins compared to their non-citrullinated counterparts. Our data indicate that citrulline-dependent T-cell response is not restricted to RA patients but that citrullination as such gives rise to a universal break in tolerance

Citrullinated vimentin as an important antigen in immune complexes from synovial fluid of rheumatoid arthritis patients with antibodies against citrullinated proteins

Introduction: Rheumatoid arthritis (RA) is an inflammatory disease, which results in destruction of the joint. The presence of immune complexes (IC) in serum and synovial fluid of RA patients might contribute to this articular damage through different mechanisms, such as complement activation. Therefore, identification of the antigens from these IC is important to gain more insight into the pathogenesis of RA. Since RA patients have antibodies against citrullinated proteins (ACPA) in their serum and synovial fluid (SF) and since elevated levels of citrullinated proteins are detected in the joints of RA patients, citrullinated antigens are possibly present in IC from RA patients. Methods: IC from serum of healthy persons, serum of RA patients and IC from synovial fluid of RA patients and Spondyloarthropathy (SpA) patients were isolated by immunoprecipitation. Identification of the antigens was performed by SDS-PAGE, mass spectrometry and immunodetection. The presence of citrullinated proteins was evaluated by anti-modified citrulline (AMC) staining. Results: Circulating IC in the serum of RA patients and healthy controls contain fibrinogen beta and fibronectin, both in a non-citrullinated form. Additionally, in IC isolated from RA SF, fibrinogen. and vimentin were identified as well. More importantly, vimentin and a minor portion of fibrinogen beta were found to be citrullinated in the isolated complexes. Moreover these citrullinated antigens were only found in ACPA+ patients. No citrullinated antigens were found in IC from SF of SpA patients. Conclusions: Citrullinated fibrinogen beta and citrullinated vimentin were found in IC from SF of ACPA+ RA patients, while no citrullinated antigens were found in IC from SF of ACPA-RA patients or SpA patients or in IC from serum of RA patients or healthy volunteers. The identification of citrullinated vimentin as a prominent citrullinated antigen in IC from SF of ACPA+ RA patients strengthens the hypothesis that citrullinated vimentin plays an important role in the pathogenesis of RA

Mapping of the Ronda peridotite massif (Spain) from AVIRIS spectro-imaging survey: A first attempt

In both AVIRIS and ISM data, through the use of mixing models, geological boundaries of the Ronda massif are identified with respect to the surrounding rocks. We can also yield first-order vegetation maps. ISM and AVIRIS instruments give consistent results. On the basis of endmember fraction images, it is then possible to discard areas highly vegetated or not belonging to the peridotite massif. Within the remaining part of the mosaic, spectro-mixing analysis reveals spectral variations in the peridotite massif between the well-exposed areas. Spatially organized units are depicted, related to differences in the relative depth of the absorption band at 1 micron, and it may be due to a different pyroxene content. At this stage, it is worth noting that, although mineralogical variations observed in the rocks are at a sub-pixel scale for the airborne analysis, we see an emerging spatial pattern in the distribution of spectral variations across the massif which might be prevailingly related to mineralogy. Although it is known from fieldwork that the Ronda peridotite massif exhibits mineralogical variations at local scale in the content of pyroxene, and at regional scale in different mineral facies, ranging from garnet-, to spinel- to plagioclase-lherzolites, no attempt has been done yet to produce a synoptic map relating the two scales of analysis. The present work is a first attempt to reach this objective, though a lot more work is still required. In particular, for the purpose of mineralogical interpretation, it is critical to relate the airborne observation to field work and laboratory spectra of Ronda rocks already obtained, with the use of image endmembers and associated reference endmembers. Also, the pretty rough linear mixing model used here is taken as a 'black-box' process which does not necessarily apply correctly to the physical situation at the sub-pixel level. One may think of using the ground-truth observations bearing on the sub-pixel statistical characteristics (texture, structural pattern, surface distribution and vegetation contribution (grass,..)) to produce a more advanced mixing model, physically appropriate to the geologic and environmental contexts

Origin of the dunitic mantle-crust transition zone in the Oman ophiolite: The interplay between percolating magmas and high-temperature hydrous fluids

International audienc

High Magnesian Dippsodote Dykes in the Oman Ophiolite : Evidence for High Temperature Hydrothermal Circulation in the Oceanic Mantle

金沢大学大学院自然科学研究科Observatoire Midi-PyreneesPromoting Environmental Pesearch in Pan-Japan Sea Area : Young Researchers\u27 Network, Schedule: March 8-10,2006,Kanazawa Excel Hotel Tokyu, Japan, Organized by: Kanazawa University 21st-Century COE Program, Environmental Monitoring and Prediction of Long- & Short- Term Dynamics of Pan-Japan Sea Area ; IICRC(Ishikawa International Cooperation Research Centre), Sponsors : Japan Sea Research ; UNU-IAS(United Nations University Institute of Advanced Studies)+Ishikawa Prefecture Government ; City of Kanazaw