Mise en place et application d'un programme technologique d'identification de nouveaux couples autoantigène - autoanticorps au cours des maladies autoimmunes

Les autoantigènes jouent un rôle majeur dans le déclenchement des maladies autoimmunes (MAI). Nous avons mis en place un programme technologique d'identification de nouveaux autoantigènes qui sont la cible des autoanticorps. Il est basé principalement sur les techniques d'identification des antigènes protéiques, c'est à dire l'immunocriblage de banques d'expression d'ADNc et l'analyse protéomique, et sur la production des protéines cibles sous forme de protéines recombinantes dans E. Coli, dans le système de cellules d'insectes/baculovirus et dans le système de transcription/traduction couplées in vitro. Ce programme a été appliqué à l'étude de la polyarthrite rhumatoïde (PR) et des pemphigus. L'immunocriblage de banques d'expression d'ADNc a permis d'identifier 2 autoantigènes : la calpastatine (précisément le domaine 1), protéine inhibitrice de protéases à cystéine, au cours de la PR et Eps15, substrat du récepteur à l'EGF, au cours des pemphigus. Le domaine 1 de la calpastatine, produit par transcription/traduction in vitro et sous forme recombinante dans E. Coli, est reconnu par 10% des sérums de malades atteints de PR. Eps15, produit sous forme recombinante dans E. Coli, est reconnu par 39% des sérums de malades atteints de pemphigus vulgaire et 36% des sérums de malades atteints de lymphome. Par analyse protéomique, nous avons montré que l'a-énolase est un autoantigène au cours de la PR. Les anticorps anti-a-énolase, mis en évidence par immunoempreinte sur un extrait de placenta humain séparé par SDS-PAGE, sont présents chez 25% des malades atteints de PR et sont spécifiques de la maladie comme nous l'a montré une étude réalisée dans une cohorte de malades atteints de rhumatismes inflammatoires récents. L'a-énolase, produite par le système de transcription/traduction in vitro qui n'effectue pas ou peu les modifications post-traductionnelles, n'est pas reconnue par les sérums de malades atteints de PR contenant des autoanticorps anti-a-énolase, démontrant ainsi l'importance de ces modifications dans l'antigénicité de la protéine.ROUEN-BU Sciences (764512102) / SudocSudocFranceF

Characterization of the Microstructure Changes Induced by a Rolling Contact Bench Reproducing Wheel/Rail Contact on a Pearlitic Steel

Understanding the effects of wheel-rail contact on the microstructure of rails is an important issue for railway management. The impact of wheel-rail contact and surface preparation on the microstructure of rails is studied using a rolling contact bench. Microstructure changes are characterized by coupling microhardness measurements and scanning electron microscopy combined with electron backscattering diffraction. This analysis led to a complete description of the sub-surface microstructure in link with the contact conditions. It was found that the use of a corroded layer on the material surface led to a considerable strain-hardening decrease. Lower surface strain-hardening was also found for sliding conditions compared to pure rolling conditions. EBSD characterizations using different indicators highlighted the importance of the scale of investigation: the use of Kernel Average Misorientation led to the identification of larger impacted depths than the Inverse Pole Figures

Development and application of a questionnaire to assess patient beliefs in rheumatoid arthritis and axial spondyloarthritis

International audienceMisinterpretation of patient beliefs may complicate shared decision-making in rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA). The objective of this study was to develop a questionnaire to assess patients’ beliefs about their disease and its treatment, and to identify patient characteristics associated with these beliefs. All beliefs reported by > 5% of 50 patients in a previous study were reformulated with a partnering patient organization into statements with which participants could rate their agreement on a scale of 0–10 (totally disagree to totally agree). The resulting Questionnaire for Arthritis Dialogue (QuAD) was made available to patients with RA or axSpA. A score ≥ 7 was considered a strongly held belief. Associations between patient characteristics and individual lifestyle beliefs were assessed using multiple logistic regression. The 21-item QuAD was completed by 672 patients (432 RA, 240 axSpA; mean [±SD] age 54.2 [± 14.2]; 63.7% female). The most widely held beliefs were related to uncertainty about progression (n = 354, 54.0%), heredity (n = 309, 47.8%), and flare triggers (n = 283, 42.7%). The unwarranted belief that physical activity is deleterious to disease activity was associated with markers of psychological distress and lower educational levels. The beliefs of patients with RA or axSpA about their disease are wide-ranging. Since these may be unwarranted and may lead to inappropriate behaviors, physicians should discuss these beliefs with their patients. The QuAD may facilitate this dialogue, and may also be useful in population studies to standardize the assessment and evolution of beliefs over time. People with long-term inflammatory conditions such as rheumatoid arthritis (RA; inflammation of the joints) and axial spondyloarthritis (axSpA; inflammation of the spine) may hold a number of beliefs about their disease, including some that are not supported by current scientific evidence (e.g., “I think that my disease was triggered by a vaccination”). Some beliefs, especially those relating to the role of lifestyle factors (such as exercise, diet, smoking, and drinking alcohol), may encourage people living with severe diseases to change their behavior in a way that has an effect on their disease. Within this project, we developed a questionnaire to identify the most common beliefs held by people living with RA or axSpA, which is called the “Questionnaire for Arthritis Dialogue (QuAD).” We also examined whether certain characteristics (or traits) of people living with RA or axSpA are linked to beliefs not currently supported by scientific evidence. A total of 672 people living with RA or axSpA in France were asked to complete the questionnaire (QuAD). The questionnaire included 21 opinion statements that they scored from 0 (totally disagree) to 10 (totally agree). A score of more than 7 was interpreted to mean that the person significantly agreed with the opinion. Based on the responses to specific opinion statements in the questionnaire, we were able to identify possible links between beliefs that are not supported by scientific evidence (e.g., “I think that flare-ups of my disease are triggered by physical effort”), and characteristics of people living with severe diseases. Our findings suggested that beliefs about lifestyle and inflammatory diseases varied from person to person, were sometimes inconsistent (the most widely held beliefs were sometimes contradictory), and were often not supported by scientific evidence. The belief that physical activity had negative effects on the disease was linked to poor education and psychological issues (such as anxiety and helplessness). People living with axSpA were more likely to believe their disease was a result of their genetic make-up, whereas those with RA more often believed their disease was caused by emotional issues. People living with axSpA were also more likely to believe that physical activity could be beneficial for their disease, and less likely to believe that their disease was caused by smoking. Our results suggest that doctors need to discuss with their patients how they might believe lifestyle is associated with their disease. This will help to dispel any unnecessary concerns, and to encourage their patients to take up healthy lifestyles and habits that are beneficial for their disease management. It may also be beneficial for health care providers to discuss the beliefs identified in this study during educational programs about inflammatory diseases, for the benefit of people living with RA or axSpA

Development and psychometric validation of a patient-reported outcome measure to assess fears in rheumatoid arthritis and axial spondyloarthritis: the Fear Assessment in Inflammatory Rheumatic diseases (FAIR) questionnaire

International audienceTo develop and validate an outcome measure for assessing fears in patients with rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA)

Periodontitis, porphyromonas, and the pathogenesis of rheumatoid arthritis

Epidemiological data indicate a link between rheumatoid arthritis (RA) and periodontal disease (PD). In vitro and in vivo studies have sought to dissect potential mechanisms by which PD may contribute to initiation and progression of RA. However, these are both multifactorial, chronic diseases, and their complex etiologies and pathogenesis themselves remain incompletely understood. Could there really be an etiological link or does this simply represent a statistical coincidence muddied by common risk factors? This review seeks to provide background on these two diseases in the context of recent discoveries suggesting that their pathogenesis may be related. In particular, the process of citrullination, a post-translational protein modification, has been highlighted as a process common to both diseases. The evidence for a relationship between the diseases is explored and its potential mechanisms discussed