Autoantibody-negative rheumatoid arthritis: still a challenge for the rheumatologist.

Increased research over the past 30 years has greatly improved the understanding of the pathophysiological mechanisms and clinical aspects of autoantibody-positive rheumatoid arthritis, resulting in improved management and outcomes. In contrast, the subset of rheumatoid arthritis that does not have autoantibodies (such as rheumatoid factor and anti-citrullinated protein autoantibodies) remains less well defined in its pathogenic mechanisms. Autoantibody-negative rheumatoid arthritis continues to pose diagnostic challenges, might respond differently to therapies, and appears to be burdened with different comorbidities and outcomes. The clear separation of rheumatoid arthritis according to serotypes is still a subject of uncertainty and controversy, and studies specifically focused on comparing rheumatoid arthritis and rheumatoid arthritis-like arthritides that do not have autoantibodies remain scarce. The purpose of this Review is to summarise the peculiarities that make autoantibody-negative rheumatoid arthritis different from its autoantibody-positive counterpart, with the aim of generating debate and stimulating further research on this challenging condition.