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Review
. 2023 Oct 31;12(4):69.
doi: 10.3390/antib12040069.

When Autoantibodies Are Missing: The Challenge of Seronegative Rheumatoid Arthritis

Marino Paroli  1 , Maria Isabella Sirinian  1
Affiliations
Review

When Autoantibodies Are Missing: The Challenge of Seronegative Rheumatoid Arthritis

Marino Paroli et al. Antibodies (Basel). .

Abstract

Seronegative rheumatoid arthritis (SNRA) is characterized by the absence of both rheumatoid factor (RF) and antibodies against the cyclic citrullinated protein (ACPA) in serum. However, the differences between the two forms of RA are more complex and have not yet been definitively characterized. Several lines of evidences support the idea that there are specific elements of the two forms, including genetic background, epidemiology, pathogenesis, severity of progression over time, and response to therapy. Clinical features that may differentiate SNRA from SPRA are also suggested by data obtained from classical radiology and newer imaging techniques. Although new evidence seems to provide additional help in differentiating the two forms of RA, their distinguishing features remain largely elusive. It should also be emphasized that the distinctive features of RA forms, if not properly recognized, can lead to the underdiagnosis of SNRA, potentially missing the period called the "window of opportunity" that is critical for early diagnosis, timely treatment, and better prognosis. This review aims to summarize the data provided in the scientific literature with the goal of helping clinicians diagnose SNRA as accurately as possible, with emphasis on the most recent findings available.

Keywords: anti-citrullinated protein antibodies; rheumatoid factor; seronegative rheumatoid arthritis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The figure summarizes the main factors described so far as being associated with seronegative rheumatoid arthritis (SNRA) or seropositive rheumatoid arthritis (SPRA). Epidemiological and environmental factors are depicted in the upper green quadrants. The yellow quadrants on either side of the figure summarize HLA and non-HLA genetic factors, microRNA (miR) expression, cells of immunity most involved in pathogenesis, and clinical features. The red quadrants at the bottom of the figure summarize the response to therapy with both conventional drugs, such as methotrexate (MTX), and biologic drugs, such as TNF inhibitors (TNFis), anti-CD20 (rituximab), and anti-CD80/86 (abatacept), as well as to Janus kinase inhibitors (JAKis).
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This research received no external funding.

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