Synovial and serum B-cell signature of autoantibody-negative rheumatoid arthritis versus autoantibody-positive rheumatoid arthritis and psoriatic arthritis.

OBJECTIVES: Autoantibody-negative rheumatoid arthritis (RA) differs from autoantibody-positive RA in several clinical aspects, possibly underpinned by pathogenetic differences. At present, the role of adaptive immune responses in autoantibody-negative RA remains unclear. Here, we investigated the synovial and serum immunophenotype indicative of B-lymphocyte involvement across the spectrum of autoantibody-positive and -negative chronic arthritides. METHODS: Ultrasound-guided synovial biopsies were retrieved from 131 patients: 43 autoantibody-positive RA, 35 autoantibody-negative RA, 25 polyarticular psoriatic arthritis (PsA), 28 oligoarticular PsA. Samples were analysed for the degree of histological inflammation, B-lymphocyte infiltration and the distribution of different pathotypes (lympho-myeloid, myeloid, pauci-immune). Serum levels of the B-cell chemoattractant CXCL13 were compared among groups. RESULTS: Synovitis scores and CD68+ sublining macrophage infiltration were comparable irrespective of clinical diagnosis and disease subtype. In contrast, the degree of B-lymphocyte infiltration and the frequency of lympho-myeloid synovitis in autoantibody-negative RA were lower than those of autoantibody-positive RA (mean [SD] 1.8 [1] vs 2.4 [0.6], p = 0.03 and 38.2% vs 62.9%, p = 0.07, respectively), and similar to polyarticular PsA. Oligoarticular PsA had the lowest B-cell scores. Serum CXCL13 was associated with lympho-myeloid synovitis and followed a similar gradient, with the highest levels in autoantibody-positive RA, intermediate and comparable levels in autoantibody-negative RA and polyarticular PsA, and low levels in oligoarticular PsA. CONCLUSIONS: The synovial and serum immunophenotype indicative of B-lymphocyte involvement in autoantibody-negative RA differs from autoantibody-positive RA and more closely resembles that observed in polyarticular PsA. The pathobiological stratification of chronic inflammatory arthritides beyond clinical diagnosis may fuel personalised treatment strategies.

The access route through the anatomical snuffbox in ultrasound-guided synovial biopsy of the wrist allows for a safe and effective collection of tissue samples in inflammatory arthritis.

BACKGROUND: A proof-of-concept study to evaluate the feasibility and safety of minimally invasive ultrasound (US)-guided synovial biopsy of the radiocarpal (RC) joint using the anatomical snuffbox as an access route. METHODS: Twenty consecutive patients with active chronic arthritis of the wrist underwent minimally invasive US-guided synovial biopsy of the RC joint using the anatomical snuffbox as the access route. Samples were retrieved from 3 predetermined biopsy target sites of the RC synovia (proximal, vault, and distal site), aiming for a minimum of 12 samples. The procedure's feasibility was evaluated based on the number and histological quality of retrieved tissue fragments tested on pre-defined histometric parameters. The safety and tolerability of the procedure were assessed through 1-week and 1-month follow-up clinical evaluations. RESULTS: A median number of 17 fragments (≥ 1 mm diameter size at macroscopic evaluation) per procedure was processed for histopathology (range 9-24) and dedicated to the study. At the histopathologic evaluation, a gradable tissue (visible lining layer and ≥ 4 fragments with IST) was recognized in 19/20 biopsies (95%), and all pre-defined histometric parameters were judged applicable and successfully measured in 19/19 gradable biopsies. All three biopsy target sites showed sampling accessibility. The entire procedure was generally well tolerated. At the 1-month follow-up, no patients showed infectious complications. CONCLUSIONS: The access route through the anatomical snuff box in US-guided synovial biopsies of the RC joint allows for a safe and targeted collection of adequate tissue samples. This modification of the traditional access route may allow easier, repeatable, and safer sampling of anatomically distinct areas of the wrist in the course of arthritis.

Insights Into the Concept of Rheumatoid Arthritis Flare.

Identification of a pathological change in the course of systemic chronic immune-inflammatory diseases is key to delivering effective treatment strategies. In this context, one of the most compelling issues is the concept of flare. The multifaceted expression of disease activity in rheumatoid arthritis (RA) makes it challenging to provide an omni-comprehensive definition of flare, encompassing the pathology's different objective and subjective domains. Our incomplete understanding of the pathophysiological mechanisms underlying this process contributes to the partial comprehension of its potential clinical expression. This review focuses on the proposed pathophysiological processes underlying disease recrudescence in RA and the variable definitions adopted to capture flare in clinical practice through its objective, subjective, and temporal domains. Overall, what emerges is a complex landscape far from being unraveled.

Clinical, Imaging, and Pathological Suppression of Synovitis in Rheumatoid Arthritis: Is the Disease Curable?

The management of patients with rheumatoid arthritis (RA) has witnessed a dramatic revolution in recent years, and disease remission has become an increasingly achievable outcome. Rheumatologists are now facing the urgent question of whether, once remission has been achieved and stably maintained, drugs can be tapered, and even discontinued. The concept of disease remission however encompasses progressive layers of complexity, all of which need to be disentangled before considering RA as a "curable" condition. As the synovial membrane represents the ultimate target of the pathological process of RA, a critical issue remains whether disease remission coincides with true suppression of inflammation and definitive tissue "healing." In this short review, we will provide a critical summary of recent studies investigating the possibility of controlling RA synovitis at the clinical, imaging or pathological level. Potential advantages and limitations of these perspectives in the definition of remission are also discussed.