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Review
. 2024 Apr 24;13(9):743.
doi: 10.3390/cells13090743.

Clinical Phenotypes, Serological Biomarkers, and Synovial Features Defining Seropositive and Seronegative Rheumatoid Arthritis: A Literature Review

James Perera  1 , Chiara Aurora Delrosso  2 , Alessandra Nerviani  1 , Costantino Pitzalis  1   3
Affiliations
Review

Clinical Phenotypes, Serological Biomarkers, and Synovial Features Defining Seropositive and Seronegative Rheumatoid Arthritis: A Literature Review

James Perera et al. Cells. .

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disorder which can lead to long-term joint damage and significantly reduced quality of life if not promptly diagnosed and adequately treated. Despite significant advances in treatment, about 40% of patients with RA do not respond to individual pharmacological agents and up to 20% do not respond to any of the available medications. To address this large unmet clinical need, several recent studies have focussed on an in-depth histological and molecular characterisation of the synovial tissue to drive the application of precision medicine to RA. Currently, RA patients are clinically divided into "seropositive" or "seronegative" RA, depending on the presence of routinely checked antibodies. Recent work has suggested that over the last two decades, long-term outcomes have improved significantly in seropositive RA but not in seronegative RA. Here, we present up-to-date differences in epidemiology, clinical features, and serological biomarkers in seronegative versus seropositive RA and discuss how histological and molecular synovial signatures, revealed by recent large synovial biopsy-based clinical trials, may be exploited to refine the classification of RA patients, especially in the seronegative group.

Keywords: rheumatoid arthritis; seronegative arthritis; synovial tissue.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Ectopic lymphoid structure in rheumatoid arthritis. Schematic representation of an ectopic lymphoid structure (ELS) with corresponding histological images of an ELS within the synovial tissue formed by B cells (CD20+ staining) and T cells (CD3+ staining), and surrounded by plasma cells (CD138+ staining). Created with BioRender.com.
Figure 2
Figure 2
Methods to refine the classification of seronegative arthritis. Diagram conveying different methods that have the potential to delineate seronegative rheumatoid arthritis into distinct endotypes. Created in BioRender.com.
See this image and copyright information in PMC

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