Pathogenic role of immune cells in rheumatoid arthritis: Implications in clinical treatment and biomarker development

Rheumatoid arthritis (RA) is a chronic, autoimmune, systemic, inflammatory disorder that affects synovial joints, both small and large joints, in a symmetric pattern. This disorder usually does not directly cause death but significantly reduces the quality of life and life expectancy of patients if left untreated. There is no cure for RA but, patients are usually on long-term disease modifying anti-rheumatic drugs (DMARDs) to suppress the joint inflammation, to minimize joint damage, to preserve joint function, and to keep the disease in remission. RA is strongly associated with various immune cells and each of the cell type contributes differently to the disease pathogenesis. Several types of immunomodulatory molecules mainly cytokines secreted from immune cells mediate pathogenesis of RA, hence complicating the disease treatment and management. There are various treatments for RA depending on the severity of the disease and more importantly, the patient’s response towards the given drugs. Early diagnosis of RA and treatment with (DMARDs) are known to significantly improve the treatment outcome of patients. Sensitive biomarkers are crucial in early detection of disease as well as to monitor the disease activity and progress. This review aims to discuss the pathogenic role of various immune cells and immunological molecules in RA. This review also highlights the importance of understanding the immune cells in treating RA and in exploring novel biomarkers

Hope for arthritis patients

Feb 2 is observed annually as Rheumatoid Arthritis (RA) Awareness Day. According to the Arthritis Foundation Malaysia, RA affects five out of every 1000 people in Malaysia regardless of age or gender. RA is characterised by the body's immune system mistakenly attacking its own joint lining, resulting in stiffness, pain and swelling. If not treated early, it may lead to joint damage and deformities over time. This year's theme. "Living Well With Rheumatoid Arthritis: Early Diagnosis, Effective Management, and a Brighter Future", underlines the importance of early diagnosis and proper management in mitigating disease progression and improving the quality of life for individuals with RA

Epstein-Barr Virus- (EBV-) Immortalized Lymphoblastoid Cell Lines (LCLs) Express High Level of CD23 but Low CD27 to Support Their Growth

Epstein-Barr virus (EBV) is one of the common human herpesvirus types in the world. EBV is known to infect more than 95% of adults in the world. The virus mainly infects B lymphocytes and could immortalize and transform the cells into EBV-bearing lymphoblastoid cell lines (LCLs). Limited studies have been focused on characterizing the surface marker expression of the immortalized LCLs. This study demonstrates the generation of 15 LCLs from sixteen rheumatoid arthritis (RA) patients and a healthy volunteer using B95-8 marmoset-derived EBV. The success rate of LCL generation was 88.23%. All CD19+ LCLs expressed CD23 (16.94-58.9%) and CD27 (15.74-80.89%) on cell surface. Our data demonstrated two distinct categories of LCLs (fast- and slow-growing) (p<0.05) based on their doubling time. The slow-growing LCLs showed lower CD23 level (35.28%) compared to fast-growing LCLs (42.39%). In contrast, the slow-growing LCLs showed higher percentage in both CD27 alone and CD23+CD27+ in combination. Overall, these findings may suggest the correlations of cellular CD23 and CD27 expression with the proliferation rate of the generated LCLs. Increase expression of CD23 may play a role in EBV immortalization of B-cells and the growth and maintenance of the EBV-transformed LCLs while CD27 expression might have inhibitory effects on LCL proliferation. Further investigations are warranted to these speculations

Aggregatibacter actinomycetemcomitans as the Aetiological Cause of Rheumatoid Arthritis: What Are the Unsolved Puzzles?

Leukotoxin A (LtxA) is the major virulence factor of an oral bacterium known as Aggregatibacter actinomycetemcomitans (Aa). LtxA is associated with elevated levels of anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients. LtxA targets leukocytes and triggers an influx of extracellular calcium into cytosol. The current proposed model of LtxA-mediated hypercitrullination involves the dysregulated activation of peptidylarginine deiminase (PAD) enzymes to citrullinate proteins, the release of hypercitrullinated proteins through cell death, and the production of autoantigens recognized by ACPA. Although model-based evidence is yet to be established, its interaction with the host&rsquo;s immune system sparked interest in the role of LtxA in RA. The first part of this review summarizes the current knowledge of Aa and LtxA. The next part highlights the findings of previous studies on the association of Aa or LtxA with RA aetiology. Finally, we discuss the unresolved aspects of the proposed link between LtxA of Aa and RA