High Degree Of Inter-Patient Heterogeneity In Synoviocyte Hyperplasia And Immune Cells Infiltration In The Synovium Of Juvenile Idiopathic Arthritis Patients

Background:Increasing evidence indicates that synovial tissue analysis can deliver pathophysiological insights but also individual clinically-relevant information in adult-onset inflammatory arthritides. Little is known about synovial pathology in juvenile idiopathic arthritis, especially regarding inter-patient variability of histopathological features.Objectives:To assess the heterogeneity of main synovial features (synoviocyte hyperplasia and immune cells infiltration) in juvenile idiopathic arthritis (JIA) patients and a cohort of young adults (<30 years old) with early rheumatoid arthritis (RA).Methods:Synovial biopsies were sampled using needle arthroscopy or ultra-sound (US) guided biopsy during intra-articular joint injection. Tissue was embedded in paraffin then sections were stained with hematoxylin and eosin. Synoviocyte hyperplasia (SH) and immune cells infiltration (ICI) was assessed by an experienced pathologist on a 0 – 3 scale where 0 represents the absence of the feature and 3 the highest level.Results:34 JIA patients (age (median ±SD): 15.5±6.47 years, oligo-articular JIA n=28/34, polyarticular JIA n=6/34, ANA-RF-ACPA positivity=56%-10%-3%) and 22 RA (age (median ±SD): 24.3±2.6 years, ANA-RF-ACPA positivity=10%-36%-32%) patients were included. Synovial tissue was obtained from knee (n=49/56), wrist (n=4/56) or metacarpophalangeal/intercarpophalangeal joints (n=3/56), using US guided biopsy in 27% of patients and needle arthroscopy in 73%.Individual scores of SH and ICI were correlated in both JIA (Spearman’s r=0.503, p value=0.0024) and RA (Spearman’s r=0.636, p value=0.0015). There was no significant difference in SH and ICI scores between the 2 groups (SH score (Q25-Q50-Q75) in JIA= 0.5-1.125-2 and in RA = 0.75-2-2; ICI score (Q25-Q50-Q75) in JIA= 1-2-2 and in RA = 0.75-2-2.25). Intra-group variability of the two assessed features was comparable between the 2 groups (SH coefficient of variation: 72.2% for JIA and 68.2% for RA; ICI coefficient of variation: 52.2% for JIA and 71.2% for RA). Within JIA patients, there was no significant difference in SH/ICI scores between groups based on ANA positivity, oligo or polyarticular involvement nor ongoing treatment.Conclusion:Studying main histological features of synovitis, we found no difference between JIA and young RA patients. Furthermore, we report a similar degree of inter-patient heterogeneity in synovial pathological features of JIA and RA patients. These variations were not explained by common clinical characteristics. Whether they relate to different molecular signatures as suggested in adult RA will be further investigated using bulk tissue RNA sequencing.Acknowledgements:This work was funded in part by Cap48 (RTBF). Clément Triaille is funded by the Fonds National de la Recherche Scientifique (FNRS, Communauté française de Belgique) and Fondation Saint-Luc (Cliniques Universitaires Saint-Luc).Disclosure of Interests:Clément Triaille: None declared, Cécile Boulanger: None declared, Tatiana Sokolova: None declared, Laurent Meric de Bellefon: None declared, Adrien Nzeusseu Toukap: None declared, Christine Galant: None declared, Nisha Limaye: None declared, Bernard Lauwerys Employee of: currently employed at UCB Biopharma, Patrick Durez: None declared.