Abstract
Biomarkers play a pivotal role in the management of rheumatoid arthritis (RA) by facilitating early diagnosis and ‘treat to the target.’ However, no gold standard biomarker has been identified for monitoring the disease activity in RA. Cytokines, a diverse group of small protein molecules secreted by peripheral blood mononuclear cells (PBMCs), play a pivotal role in pathogenesis and disease progression in RA. Research is currently underway to find out the applicability of cytokines as biomarkers in RA. This study aimed to quantify the PBMCs that secrete four types of cytokines; TNF-α, IL-1β, IL-10 and IL-17A in two cohorts of active RA patients (early RA patients and established RA patients), compared to healthy controls (HC), using the enzyme-linked immunosorbent spot (ELISPOT) assay, and to assess their association with measures of disease activity of RA. Patients were recruited from outpatient rheumatology clinics, and the disease activity was assessed using single and composite measures of disease activity. The cytokine expression was evaluated using freshly separated PBMCs from whole blood of RA patients using the ELISPOT assay. The number of PBMCs (counted as spot-forming cells (SFCs) per 105 PBMCs) that secreted the cytokine of interest were statistically significantly higher in early RA patients, compared to HC, for IL-17A (P<0.05). Such an increased number of SFCs was not observed in the established RA group, compared to controls, for any of the cytokines tested. The correlation analysis showed that IL-17A is having a moderate correlation (Spearman`s ρ, p <0.05) with five clinical measures of disease activity, including disease activity score 28 (DAS28). According to the multivariable linear regression models, IL17A was a good predictor of both the disease activity score 28 (DAS28) and clinical disease activity index (CDAI). In conclusion, IL-17A has potential applicability as a biomarker of disease activity of RA.
Highlights
Rheumatoid arthritis (RA) is a chronic systemic autoimmune joint disease that leads to joint inflammation, deformity, and loss of function [1]
This study aimed to assess the expression of TNF-α, IL-1β, IL-10 and IL-17A by peripheral blood mononuclear cells (PBMCs) in two cohorts of active RA patients (DMARDS naïve, early RA patients and established RA patients who are on Disease-modifying antirheumatic drugs (DMARD)), compared to healthy controls, using enzyme-linked immunosorbent spot (ELISPOT) assay, and to assess their associations with clinical markers of RA disease activity and erythrocyte sedimentation rate (ESR)
It was observed that the number of IL-17A spot-forming cells (SFC) were higher in DMARDs naïve early RA patients compared to healthy controls (HC)
Summary
Rheumatoid arthritis (RA) is a chronic systemic autoimmune joint disease that leads to joint inflammation, deformity, and loss of function [1]. Biomarkers are chemical, physical, or biological measures that can be used in refining the diagnosis, measuring the disease progression, or predicting and monitoring the effects of treatment [4]. ACPA and RF are useful in terms of diagnosis and predicting disease progression. In a study carried out by Kay et al, among 9,135 with active RA, 58% of patients had elevated levels of neither ESR nor CRP. Composite measures such as disease activity score 28 (DAS 28) and simplified disease activity index (SDAI) has integrated many dimensions of the disease to quantify disease activity of RA [7, 8].
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