Synovial Cellular and Molecular Signatures Stratify Clinical Response to csDMARD Therapy and Predict Radiographic Progression in Early Rheumatoid Arthritis Patients

Copyright © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.
Annals of the Rheumatic Diseases. 2019 Jun;78(6) doi: 10.1136/annrheumdis-2018-214539. Epub 2019 Mar 16.

Abstract

OBJECTIVES:
To unravel the hierarchy of cellular/molecular pathways in the disease tissue of early, treatment-naïve rheumatoid arthritis (RA) patients and determine their relationship with clinical phenotypes and treatment response/outcomes longitudinally.
METHODS:
144 consecutive treatment-naïve early RA patients (<12 months symptoms duration) underwent ultrasound-guided synovial biopsy before and 6 months after disease-modifying antirheumatic drug (DMARD) initiation. Synovial biopsies were analysed for cellular (immunohistology) and molecular (NanoString) characteristics and results compared with clinical and imaging outcomes. Differential gene expression analysis and logistic regression were applied to define variables correlating with treatment response and predicting radiographic progression.
RESULTS:
Cellular and molecular analyses of synovial tissue demonstrated for the first time in early RA the presence of three pathology groups: (1) lympho-myeloid dominated by the presence of B cells in addition to myeloid cells; (2) d iffuse-myeloid with myeloid lineage predominance but poor in B cells nd (3) pauci-immune characterised by scanty immune cells and prevalent stromal cells. Longitudinal correlation of molecular signatures demonstrated that elevation of myeloid- and lymphoid-associated gene expression strongly correlated with disease activity, acute phase reactants and DMARD response at 6 months. Furthermore, elevation of synovial lymphoid-associated genes correlated with autoantibody positivity and elevation of osteoclast-targeting genes predicting radiographic joint damage progression at 12 months. Patients with predominant pauci-immune pathology showed less severe disease activity and radiographic progression.
CONCLUSIONS:
We demonstrate at disease presentation, prior to pathology modulation by therapy, the presence of specific cellular/molecular synovial signatures that delineate disease severity/progression and therapeutic response and may pave the way to more precise definition of RA taxonomy, therapeutic targeting and improved outcomes.

Imaging in Rheumatoid Arthritis: The Role of Magnetic Resonance Imaging and Computed Tomography.

Abstract

In suspected and diagnosed rheumatoid arthritis (RA), magnetic resonance imaging (MRI) allows detection of all relevant pathologies, such as synovitis, tenosynovitis, bone marrow edema (osteitis), bone erosion and cartilage damage. MRI is more sensitive than clinical examination for monitoring disease activity (i.e., inflammation) and more sensitive than conventional radiography and ultrasonography for monitoring joint destruction. In suspected RA, MRI bone marrow edema predicts development of RA, and in early RA patients, it predicts subsequent structural damage progression. CT is the standard reference imaging modality for visualizing bone damage, including bone erosions in RA, but lacks sensitivity for soft-tissue changes, including synovitis and tenosynovitis. CT has a minimal role in RA clinical trials and practice, except in selected patients where MRI is contraindicated or not available or if crystal arthritis such as gout or pseudo-gout is suspected. MRI has documented utility in diagnosis, monitoring and prognostication of patients with RA and is increasingly used for these purposes in clinical practice and particularly clinical trials.

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Maecenas tempor, ex at maximus efficitur, felis sem ultrices ligula, ut hendrerit purus eros ac urna. Vestibulum ut vestibulum tortor. Orci varius natoque penatibus et magnis dis parturient montes, nascetur ridiculus mus. Cras eu lectus quam. Nunc ligula arcu, auctor sit amet tellus eleifend, facilisis laoreet odio. Donec placerat urna eleifend blandit porttitor.

Nunc magna turpis, tristique at dictum vel, sollicitudin blandit felis. Morbi aliquam elit et pellentesque vulputate. Donec elementum, ante quis ornare porttitor, tortor dolor vestibulum velit, et viverra enim massa vitae ex.