PhD defense of Xavier ROMAND on 02/04/22

PhD defense of Xavier Romand from T-RAIG team on february 2022, the 4th at 2pm:

" Study of pathogenic pathways involving innate immunity in spondyloarthritis. "

bullet Jury:

  • Pr. Athan BAILLET, Professeur des Universités – Praticien Hospitalier, Université Grenoble Alpes, Director
  • Pr. Bertrand TOUSSAINT, Professeur des Universités – Praticien Hospitalier, Université Grenoble Alpes, President
  • Pr. Corinne MICELI, Professeur des Universités – Praticien Hospitalier, Université Paris Centre, Reporter
  • Pr. Marie-Elise TRUCHETET, Professeur des Universités – Praticien Hospitalier, Université de Bordeaux, Reporter
  • Pr. Daniel WENDLING, Professeur des Universités – Praticien Hospitalier, Université de Franche-Comté, Examiner
  • Pr. Philippe GAUDIN, Professeur des Universités – Praticien Hospitalier, Université Grenoble Alpes, Examiner

bullet  Key words:  

Spondyloarthritis, Reactive arthritis, Chlamydia, Macrophage, Calprotectin

bullet Abstract:

Spondyloarthritis is a frequent and severe chronic inflammatory rheumatic disease that can lead to permanent joint damage which is difficult to predict. The mechanisms underlying the breakdown between a healthy state and the onset of spondyloarthritis are insufficiently understood. The most recent data show that intestinal dysbiosis and type 3 innate immunity play a key role in the development of this disease. In order to study this rupture of tolerance induced by bacterial agents, we studied reactive arthritis, a subgroup of spondyloarthritis triggered by a specific bacterial agent. The study of the SKG mouse model of Chlamydiainduced reactive arthritis allowed us to identify that macrophages are both involved in the development of TNF-, IL-17- and IL-23-mediated arthritis and in the transport of Chlamydia from the genital tract to peripheral organs. This thesis highlights that the study of animal models leads to a better understanding of the mechanisms involved in chronic inflammatory rheumatic diseases. One of the major objectives of treatments in spondyloarthritis is to improve the function of the patient. In order to facilitate the study of this parameter in small animals, we propose a new innovative approach that allows to efficiently evaluate the functional impact, by limiting human interventions, using digital connected cages. It is still difficult to discriminate patients at risk of developing the most severe forms of SpA. The future will be to better identify these patients in order to propose a personalized therapeutic approach. In view of the involvement of innate immunity in these inflammatory rheumatic diseases, we studied the interest of serum calprotectin (S100A8/A9 protein), a biomarkers excreted by monocytes and neutrophils. We show that serum calprotectin is a biomarker of activity in early spondyloarthritis, providing indirect evidence of myeloid cell involvement in this disease. However, serum calprotectin fails to identify patients at risk of structural progression. We then studied this biomarker in neutrophil anti-cytoplasm antibody (ANCA) vasculitis, a neutrophil-mediated disease. We found that increased serum calprotectin levels during remission maintenance therapy is associated with the risk of a decline in renal function suggesting the potential interest of this biomarker in the follow-up of patients with ANCA vasculitis. In addition to joint damage, cardiac damage such as aortic valve disease and myocardial injury have been described in spondyloarthritis. Through a meta-analysis, we have shown that the prevalence of valvulopathy on echocardiography in axial spondyloarthritis is comparable to healthy subjects. However, there is an alteration of certain parameters in favor of a left ventricular diastolic dysfunction. The clinical significance remains to be clarified before proposing this examination in routine. Finally, in order to improve the management of patients with spondyloarthritis, we propose in this thesis a list of variables to be collected and reported systematically after the diagnosis and during the follow-up of axial spondyloarthritis in daily practice.