POS0743 THE DIAGNOSTIC AND PROGNOSTIC ROLE OF SYNOVIAL TISSUE ANALYSIS IN JUVENILE IDIOPATHIC ARTHRITIS: A MONOCENTRIC STUDY

• Published in: Annals of the rheumatic diseases Vol. 82; no. Suppl 1; pp. 661 - 662
• Main Authors: Costi, S., Armiraglio, E., Pregnolato, F., Chighizola, C., Marino, A., Iannone, C., Amati, A., Randelli, P., Parafioriti, A., Caporali, R.
• Format: Journal Article
• Language: English
• Published: Kidlington BMJ Publishing Group Ltd and European League Against Rheumatism 01.06.2023; Elsevier B.V; Elsevier Limited
• Subjects: Arthritis; Biopsy; CD103 antigen; CD20 antigen; CD3 antigen; CD69 antigen; Diagnosis; Edema; Fibrin; Fibrosis; Immunohistochemistry; Inflammation; Inflammatory arthritides; Lymphocytes B; Medical records; Patients; Pediatrics; Prognostic factors; Psoriatic arthritis; Rheumatoid factor; Scientific Abstracts; Synovitis; Synovium; Inflammatory arthritides; Synovium; Prognostic factors
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2023-eular.6248

BackgroundJuvenile idiopathic arthritis (JIA) refers to arthritis persisting for more than 6 weeks and presenting before 16 years. Once the diagnosis of JIA has been formulated, clinicians face challenges in tailoring the therapeutic approach upon each patient’s clinical features. To date, no study has addressed the role of synovial pathobiology to support the diagnostic approach and guide clinical management in children.ObjectivesThis study aimed at investigating the diagnostic role of synovial biopsy in children presenting with arthritis and assess the prognostic significance of synovial histology in predicting clinical outcomes among patients with JIA.MethodsMedical records of pediatric patients undergoing synovial biopsy between 1995 and 2020 were retrospectively reviewed. Synovial samples were analyzed histologically and immunohistochemically.ResultsOf 99 patients included, synovial biopsy was performed for diagnostic purposes in 65 cases allowing to correctly classify 79% of patients. At histological analysis on 42 JIA samples, any difference emerged between JIA subsets (Table 1) or treatment-naïve and treatment-experienced subjects. Tissue analysis predicted subsequent disease course: higher number of layers of synovial lining predicted a worse disease course (>4 flares during follow-up) (median 4.5 [IQR 3.0] vs. 3.0 [IQR 2.5], p=0.035), even after adjusting for age at diagnosis and observation time (OR 2.2, 95% CI 1.3-3.9, p=0.007); subjects who had switched >2 bDMARDs had higher prevalence of subsynovial elementary lesions (55.6% vs 10.3%, p=0.005) and fibrin deposits in synovial lining (60.0% vs 22.6%, p=0.049), even after adjustment for observation time and age at diagnosis (OR 8.1, 95% CI 1.03-64.2, p=0.047). At immunohistochemistry on 31 JIA samples, higher CD3 expression was described in polyarticular compared to oligoarticular subset (p=0.040), while no differences were found between persistent and extended oligoarticular subsets (p=0.670). Patients with severe disease course had higher CD20+ cells percentage (OR 7, 95% CI 1.4–35.5, p=0.023), regardless of JIA subset and treatment exposure (Figure 1).ConclusionThe present study offers several novel insights into the potential role of synovial pathobiology in JIA. Synovial tissue analysis might support the clinicians in the diagnostic approach of pediatric patients presenting with arthritis and guide the clinical management of JIA.Table 1.Synovial morphological and immunohistochemical features in the overall population and within JIA subtypes.OligoPoli RF-ERAPsASystemicOverall populationMorphologicLayers of synovial lining (score), median (IQR)3.0 (2.0)(n=26)2.8 (2.4)(n=6)6.0 (3.0)(n=4)5.5 (0.0)(n=1)4.0 (1.0)(n=3)3.5 (2.6)(n=40)Subsynovial elementary lesions, % (n)n=24n=6n=4n=1n=3n=38Edema33 (8)50 (3)25 (1)0 (0)0 (0)32 (12)Fibrosis50 (12)50 (3)50 (2)0 (0)33 (1)47 (18)Edema+fibrosis17 (4)0 (0)25 (1)100 (1)67 (2)21 (8)Fibrin deposit, % (n/N)33 (9/27)17 (1/6)25 (1/4)0 (0/1)67 (2/3)32 (13/41)Krenn synovitis score, median (IQR)6.0 (1.5)(n=24)5.0 (3.5)(n=6)6.0 (2.3)(n=4)7.0 (0.0)(n=1)7.0 (2.5)(n=3)6.0 (3.0)(n=38)Inflammatory infiltrate (score), median (IQR)2.0 (1.0)(n=27)1.5 (1.0)(n=6)2.0 (1.0)(n=5)2.0 (0.0)(n=1)2.0 (1.0)(n=3)2.0 (1.0)(n=42)Immunohistochemistryn=22n=5n=3n=1n=0n=31CD3 ≥40%% (n)41 (9)100 (5)33 (1)0 (0)-48 (15)CD20 ≥40%% (n)32 (7)20 (1)67 (2)0 (0)-32 (10)CD69 ≥40%% (n)23 (5)40 (2)0 (0)0 (0)-23 (7)CD103 ≥40%% (n)5 (1)0 (0)0 (0)0 (0)-3 (1)JIA= juvenile idiopathic arthritis; Oligo= oligoarticular; Poly FR -= polyarticular rheumatoid factor negative; ERA= enthesitis arthritis; PsA= psoriatic arthritis.Figure 1.(A) CD3+ infiltrate in oligoarticular and polyarticular JIA; (B) CD3+ infiltrate in persistent and extended oligoarticular JIA; (C) Correlation between the percentage of CD20+ B cells and the severity of disease in all JIA subtypes; (D) Correlation between the percentage of CD20+ B cells and the severity of disease in oligoarticular group only.AcknowledgementsThis manuscript is dedicated to the memory of Prof. Rolando Cimaz, an inspiring mentor and beloved friend.Disclosure of InterestsStefania Costi: None declared, Elisabetta Armiraglio: None declared, Francesca Pregnolato: None declared, Cecilia Chighizola: None declared, Achille Marino: None declared, Claudia Iannone: None declared, Andrea Amati: None declared, Pietro Randelli: None declared, Antonina Parafioriti: None declared, Roberto Caporali Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Fresenius, Galapagos, Janssen, Lilly, Novartis, Pfizer, UCB, Consultant of: AbbVie, Fresenius, Galapagos, Lilly, Novartis, Pfizer, UCB.