Abstract
ObjectiveIt has been demonstrated that early treatment of rheumatoid arthritis (RA) patients prevents further joint damage and disability, but biomarkers enabling early RA to be distinguished within the undifferentiated arthritis (UA) cohort are still being sought.PurposeThe aim of the research was to study the pathomechanism of initiation and progression of UA→RA and to find such new predictive biomarkers on the basis of functional studies of the immune system.Methods55 patients with UA were enrolled into the study and followed up for 2 years. The dynamic parameters of proliferation of the peripheral blood CD4+ T cells were recorded at the UA stage. During the follow-up study, standard diagnostic procedures were performed to make the final diagnosis. Comparison of the CD4+ T cell proliferation parameters in the UA-RA and UA-non-RA patients was conducted after the final diagnosis was established.ResultsOur studies showed that the G0-G1 transition time, the cell cycle duration, the number of cell divisions per dividing CD4+ cells and the percentage of dividing CD4+ T cells differed significantly between UA-RA and UA-non-RA patients. Moreover, these proliferation parameters achieved higher specificity and sensitivity in the detection of early RA within UA patients compared to the routine serological tests available.ConclusionThe proliferation parameters of CD4+ T cells reflect central pathophysiological changes in RA and can be used as new biomarkers for early RA diagnosis, which would enable the international rheumatology recommendation to be achieved concerning the early diagnosis and treatment of RA patients.
Highlights
The term “undifferentiated arthritis” (UA) is applied to the most common type of arthritis at the early stage when, in the absence of current recommended diagnostic criteria, it cannot be classified into the well-known clinical disease categories of defined inflammatory rheumatic diseases [1]
During clinical 2-year prospective follow-up study of 55 UA patients (Fig. 1), 50 (91 %) of them fulfilled the diagnostic criteria for specific rheumatic disease including: rheumatoid arthritis (RA), primary Sjögrens syndrome, psoriatic arthritis, polyarthralgiaassociated thyroiditis, spondyloarthritis positive for human histocompatibility leukocyte B27 antigen (HLA-B27) antigen, reactive arthritis, rhupus and osteoarthritis
Basic clinical characteristics at baseline were compared between early RA (UA-RA) and patients who developed other rheumatic diseases (UA-non-RA), divided according to final diagnosis (Table I)
Summary
The term “undifferentiated arthritis” (UA) is applied to the most common type of arthritis at the early stage when, in the absence of current recommended diagnostic criteria, it cannot be classified into the well-known clinical disease categories of defined inflammatory rheumatic diseases [1]. At the stage identified as UA, identification of the subset of patients destined to develop rheumatoid arthritis (RA) - the most severe and persistent form of rheumatic disease - is a challenge for both clinicians and researchers. The new diagnostic approach would allow disease-modifying anti-rheumatic drugs (DMARDs) to be introduced as an early treatment strategy [2]. In line with European League Against Rheumatism/American College of Rheumatology recommendation, the concept of a “window of opportunity” for the treatment of the patients should be acted upon as early as possible [4].
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