Invited Speaker Australian Society for Microbiology Annual Scientific Meeting 2018

Can we develop of a diagnostic assay to detect and monitor rheumatic heart disease? (#158)

Brenda Govan 1 , Georgina Price 1 , Catherine Rush 1 , Robert Norton 2 , Natkunan Ketheesan 3
  1. James Cook University, Townsville, QLD, Australia
  2. Microbiology, The Townsville Hospital, Townsville, QLD, Australia
  3. University of New England, Armidale, QLD, Australia

Rheumatic Heart Disease (RHD) is the chronic heart valve damage caused by episodes of acute rheumatic fever (ARF) which can occur following repeat infections with Group A Streptococcus (GAS). The burden of ARF and RHD is significant and borne exclusively by the socioeconomically disadvantaged. Its stark distribution across socio-economic lines is manifested in the glaring global disparities in prevalence between developing and developed countries and within developed countries such as Australia and New Zealand, between the indigenous and non-indigenous populations.

Despite the impact, there are significant gaps in the understanding of RF/RHD pathology. A proposed mechanism of the autoimmune activity in RF/RHD is cross-reactivity of anti-GAS M protein antibodies with host proteins such as cardiac myosin (CM) in the heart.  It is hoped that increased understanding of this aspect of ARF/RHD pathogenesis could lead to the development of an auto-antibody based test to detect and potentially monitor ARF/RHD heart damage.

Using the Rat Autoimmune Valvulitis model of ARF/RHD, the aims of this study were to map GAS M protein stimulated antibodies to particular regions within the S2 sub-fragment of CM and to demonstrate an association between antibody reactivity to these S2 regions and the development of valvulitis as evidenced by echocardiographic (Echo), electrocardiographic (ECG) and histological findings.

Lewis rats were injected with either pooled peptides, recombinant GAS M5 protein or porcine CM (pCM). Enzyme-linked immunoassay found significant elevation of IgG reactive to two S2 peptides in the sera of rats injected with rM5.  Examination of P-R intervals on ECG found statistically significant elongation in groups administered repeat injections of pooled peptides. Collectively, all Echo, ECG and histology findings demonstrated the development of valvulitis in the rats, concurrent with the presence of elevated serum IgG reactivity to the S2 sub-fragment. These two epitopes, along with other’s identified in previous studies, warrant further examination of their sensitivity and specificity to ARF/RHD in human RF/RHD patients.