An immunological perspective on rheumatic heart disease pathogenesis: more questions than answers
- Author(s)
- Bright, PD; Mayosi, BM; Martin, WJ;
- Journal Title
- Heart
- Publication Type
- Journal Article in press
- Abstract
- Acute rheumatic fever (ARF) and the related rheumatic heart disease (RHD) are autoimmune diseases thought to be triggered by group A streptococcal (GAS) pharyngitis. RHD is a leading cause of mortality in the developing world. The strong epidemiological association between GAS throat infection and ARF is highly suggestive of causation, but does not exclude other infections as contributory. There is good evidence of both humoral and cellular autoreactivity and GAS/self cross-reactivity in established RHD. RHD pathogenesis could feasibly be triggered and driven by humoral and/or cellular molecular cross-reactivity between GAS and host cardiac tissues (molecular mimicry). However, good evidence of humoral pathogenicity is lacking and the specific triggering event for RHD remains unknown. It is likely that the critical immunological events leading to ARF/RHD occur at the point of contact between GAS and the immune system in the throat, strongly implicating the mucosal immune system in RHD pathogenesis. Additionally, there is circumstantial evidence that continued live GAS may play a role in ARF/RHD pathogenesis. We suggest that future avenues for study should include the exclusion of GAS components directly contributing to RHD pathogenesis; large genome-wide association studies of patients with RHD looking for candidate genes involved in RHD pathogenesis; genome-wide association studies of GAS from patients with ARF taken at diagnosis to look for characteristics of rheumatogenic strains; and performing case/control studies of GAS pharyngitis/ARF/patients with RHD, and controls to identify microbiological, immunological and environmental differences to elucidate RHD pathogenesis.
- Publisher
- BMJ
- Research Division(s)
- Inflammation
- PubMed ID
- 27260192
- Publisher's Version
- https://doi.org/10.1136/heartjnl-2015-309188
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2016-06-16 12:25:10
Last Modified: 2016-06-16 12:27:12