Elevated levels of IgG specific antimyosin antibodies in acute rheumatic fever (ARF): differential profiles of antibodies to myosin and soluble myocardial antigens in ARF, acute glomerulonephritis and group A streptococcal pharyngitis

Abstract

Group A streptococcus is the common etiologic agent associated with group A streptococcal pharyngitis (SAP) and its sequelae: acute rheumatic fever (ARF) and acute glomerulonephritis (AGN). However, hyperresponsiveness to cardiac antigens stemming from the shared antigenic determinants with streptococcal antigens is believed to play a role only in the pathogenesis of ARF. A Profile of IgM and IgG immune responses to soluble myocardial antigen (SMA) and myosin was evaluated in ARF, AGN and SAP. A modified ELISA measuring the area under curve (AUC) for quantitation of antibodies to SMA and rabbit muscle myosin was employed. Proteins in the SMA were resolved by SDS-PAGE. Immune responses to a major protein band of congruent to 205 kD, corresponding to the molecular weight of the heavy chain of cardiac myosin was also evaluated. In the ARF group while a significant elevation of both IgM and IgG anti-SMA antibody levels was observed, only antibodies of IgG isotype were elevated against rabbit muscle myosin and 205 kD protein of human cardiac tissue in comparison with normal controls, AGN and SAP groups. There was a significant positive correlation of antibodies against skeletal muscle myosin with antibodies against 205 kD protein of human cardiac tissue for both IgM and IgG specificities in ARF alone. The incidence of positive sera (values greater than mean + 2SD of control values) for IgM and IgG anti-SMA and antimyosin antibodies was higher in ARF than in AGN and SAP. None of the AGN and SAP sera had elevated levels of antibodies against SMA whereas low incidence of positive sera for antimyosin antibodies was observed in these groups. Although group A streptococcus etiology is associated with ARF, AGN and SAP, differential profiles of immune responses to cardiac antigens is observed in these diseases. Elevated IgG specific response to myosin and 205 kD cardiac protein was demonstrated in ARF and not in other groups with a similar etiology. It may be worthwhile, therefore to explore the possibility of using this as an additional parameter in diagnosis of ARF.