Hanin N. AlHiraky

Cardio-rheumatology is an evolving and interdisciplinary field lying at the intersection of rheumatology and cardiovascular medicine that recognizes that individuals with autoimmune and inflammatory rheumatic complications have a much higher likelihood of developing cardiovascular diseases (CVDs). Inflammasomes are multiprotein complexes stimulated by the immune system after the detection of pathogens or cellular injury. Inflammasomes undergo a two-stage activation process initiated by nuclear factor (NF)-κB, subsequently playing a crucial role in innate immunity through activation of caspase 1 and the consequent release of proinflammatory cytokines such as IL-18 and IL-1β. However, a loss of control of inflammasome activation can cause inflammatory diseases in humans. Recent studies have focused on the role of inflammasomes in inflammatory cascades implicated in the pathogenesis of several diseases. Here, we review inflammasome activation, its mechanism of action, and its role in CVD. In particular, we describe the role of inflammasomes in rheumatic heart disease, Kawasaki disease, familial Mediterranean fever, ankylosing spondylitis, and rheumatoid arthritis as exemplars to illustrate pathobiological mechanisms and the potential for targeting inflammasomes for therapeutic benefit.

Rheumatic heart disease (RHD) is the most important sequela of upper respiratory group A Streptococcus (GAS) infection. The role of the common angiotensin-converting enzyme (ACE) insertion/deletion (I/D) variant in the disease and its subtypes remains uncertain. The acute-phase reactants (APRs) C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) form part of the Jones criteria for diagnosing RHD, and genetic factors are known to influence baseline CRP and ESR levels. Therefore, here, we investigated the relationship between the ACE I/D polymorphism and APR levels in RHD. A total of 268 individuals were recruited, including 123 RHD patients and 198 healthy controls. There was a trend toward a higher D allele frequency in RHD patients. The ACE I/D polymorphism genotype frequency and DD+ID allelic carriage were significantly associated with a high APR level (p = 0.04 and p = 0.02, respectively). These results highlight the importance of ACE I/D polymorphisms in RHD for disease stratification, but not for disease predisposition. Further studies in larger cohorts and different populations are now required to confirm this association and to explore the mechanism of this effect.