Adipocytokines, Receptor Activator of Nuclear Factor-κB Ligand, and Midkine: Intricate Biomarkers Network Involved in Pathogenesis and Activity of Rheumatoid Arthritis in Egyptians

Background: Rheumatoid arthritis (RA) is a common autoimmune disease in which a heterogeneous course and different pathogenic mechanisms are implicated in the development of chronic inflammation and subsequent joint damage. Early diagnosis and timely detection of RA progression are of global challenges. However, the lack of sensitivity of the currently available biomarkers has impaired the ability to implement potentially effective therapy in a timely manner. Adipocytokines such as adiponectin, and visfatin have recently emerged as pro-inflammatory mediators involved in the pathophysiology of RA, however they still a matter of debate.

Aim: This current study went further to investigate the roles of Adipocytokines, receptor activator of nuclear factor kappa-B ligand (RANKL) levels and midkine (MDK) gene expression axis in patients with early untreated RA and their implication in disease activity monitoring.

Methodology: Forty newly diagnosed untreated patients with RA (20 patients with active RA and 20 patients with inactive RA) in addition to twenty apparently healthy age, sex and race matched controls were enrolled in this study. Serum tumor necrosis factor-alpha (TNF-α), adiponectin, visfatin and RANKL levels by immunoassay and MDK mRNA level in peripheral blood by real-time PCR were assessed.

Results: TNF-α, adiponectin, visfatin and RANKL levels as well as peripheral blood MDK mRNA levels were significantly increased in patients RA with higher values were for active RA with significant positive correlations to disease activity score 28 (DAS-28).

Conclusion: Adipocytokines, RANKL and MDK axis has a role in RA pathogenesis, early diagnosis and disease activity. These results may open new avenues for developing preventive and therapeutic strategies for RA.