Acute Rheumatic Fever (ARF) and
Rheumatic Heart Disease (RHD) are autoimmune sequelae of Group A Streptococcus
infection with significant global disease burden. The pathogenesis of these diseases is poorly understood, and no immune modulating
therapies are available to stop progression from ARF to RHD.
Cytokines and
chemokines are immune signaling molecules critical to the development of
autoimmune diseases. An increasing number of studies point to a central role for pro-inflammatory
cytokines and
chemokines in ARF and RHD pathogenesis, in particular
IL-6, IL-8/CXCL8, and TNFα, which are elevated in circulation in both ARF and RHD patients. Histological studies of RHD valve tissue implicates Th1 and Th17 associated pro-inflammatory
cytokines,
chemokine CXCL9, and the
fibrosis-associated
cytokine TGF-β in progressive cycles of inflammatory damage and fibrotic repair. Taken together, this suggests immune molecules contribute to both the acute inflammatory disease stage of ARF, as well as cardiac remodeling and valve dysfunction in RHD.
Monoclonal antibody blockade of pro-inflammatory
cytokines IL-6 and TNFα are approved
therapies for many
autoimmune diseases and the most successful immunomodulating
therapies for
rheumatoid arthritis. Current evidence suggests possible benefit for ARF patients from
IL-6 and TNFα blockade, in particular to interrupt progression to RHD, and warrants immediate investigation.