Dissociation between systemic inflammation and symptom burden in rheumatoid arthritis: biomarker – clinical discordance in an African population

Abstract

The relationship between systemic inflammation, autoimmunity, and patient-reported outcomes in individuals with rheumatoid arthritis (RA) remains poorly understood, particularly in African communities experiencing delayed diagnoses and limited access to biological treatments. This study aimed to evaluate the relationships among circulating inflammatory biomarkers, disease activity, and patient-reported outcomes in a cohort of individuals attending Kenyatta National Hospital in Kenya. We conducted a case–control study involving 44 patients with RA and 44 healthy controls at the Kenyatta National Hospital. We measured plasma levels of cytokines (tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interleukin 1 beta (IL-1)), autoantibodies anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF), and acute-phase reactants C-reactive protein (CRP) using standard enzyme-linked immunosorbent assay (ELISA) kits and erythrocyte sedimentation rate (ESR). Disease activity was assessed using the disease activity score-28 with erythrocyte sedimentation rate (DAS28-ESR), while patient-reported outcomes were captured using the pain visual analogue scale, health assessment questionnaire, and duration of morning stiffness. Statistical analyses involved Spearman’s correlations, receiver operating characteristic (ROC) curves, and multiple linear regression. All biomarker levels (ACPA, CRP, RF, IL-1β, IL-6, and TNF-α) were significantly higher in patients with RA than in controls (p < 0.001). Strong correlations were observed between inflammatory biomarkers (ACPA-CRP ρ = 0.70) and joint counts (ACPA-tender joints ρ = 0.56). ESR demonstrated the greatest discriminative ability for both high disease activity (AUC = 0.778) and severe pain (AUC = 0.775), whereas cytokines performed poorly (AUC < 0.60). Multiple regression revealed that ESR (β = 0.67) and tender joint count (β = 0.54) were the strongest predictors of DAS28-ESR (R2 = 0.92). This study revealed a significant dissociation between systemic inflammation and patient-reported symptoms in individuals with RA. Although biomarkers, such as ESR, autoantibodies, and cytokines, effectively reflect inflammatory burden and disease activity, they are poorly correlated with pain and functional outcomes. These findings highlight the multifactorial nature of RA symptoms and support the need for integrated assessment strategies that combine objective biomarkers with patient-reported measures to guide comprehensive therapeutic approaches. Study limitations included a modest sample size and a predominantly late-stage disease cohort.