Background: Rheumatoid arthritis (RA) is a persistent autoimmune condition defined by widespread synovial tissue inflammation and structural joint deterioration, with an estimated global prevalence between 0.5% and 3%. The disease predominantly targets synovial joints, resulting in progressive functional impairment when therapeutic intervention is delayed or inadequate. Objective: This review aims to comprehensively examine the contributing risk factors, underlying pathophysiological processes, and recently developed immunoengineering-based therapeutic strategies applicable to the clinical management of rheumatoid arthritis. Methods: A structured review of peer-reviewed literature was undertaken through PubMed, utilizing a targeted search strategy incorporating the terms ‘rheumatoid arthritis’ and ‘immunoengineering.’ Filters were applied to restrict results to English-language publications from peer-reviewed sources. The review emphasized studies investigating genetic susceptibility, environmental determinants, immune cell behaviour, and novel therapeutic advances in RA management. Results: Multiple interdependent risk factors underpin RA development, most notably genetic variants including HLA-DRb1 alleles, alongside demographic influences such as biological sex and advancing age, as well as obesity and pathogenic microbial exposure. These factors collectively initiate a self-amplifying inflammatory process characterized by protein citrullination and the subsequent generation of anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF). The ensuing immune dysregulation—driven principally by monocyte and T-lymphocyte infiltration—propagates synovial inflammation and progressively destroys cartilaginous and bony structures. Conclusions: While considerable progress has been achieved in RA pharmacotherapy, existing treatments remain constrained by systemic side effects and incomplete therapeutic responses. Emerging immunoengineering strategies offer a targeted approach to modulating the molecular and immunological milieu of affected joints, providing improved therapeutic precision. Continued investigation in this area is anticipated to yield novel clinical pathways capable of substantially enhancing patient outcomes in rheumatoid arthritis care.
Makkar et al. (Mon,) studied this question.