Streptococcal Anti-Phospholipid Antibody, MAb10F5, Binds Greatest in the Cardiac Valve Region

Abstract

An autoimmune related inflammation occurring after group A streptococcal infection is believed to be behind the development of rheumatic heart disease. The group A streptococcal conservative M protein sequence when injected into mice generates a promiscuous antibody referred to as mAb10F5. Injection of the M protein sequence into Lewis rats results in heart manifestations and injection of mAb10F5 which is against M protein sequence into Lewis rats results in the display of the antibody in the heart, especially in the valve region. The binding of mAb10F5 in the heart resembles that of anti-cardiac myosin with binding in all three regions of the heart examined (artial, valve and ventricular apex) during the first 72 hrs after injection. However, mAb10F5 remains significantly bound in the valve region at 72 hrs while binding of anti-cardiac myosin binding decreases. MAb10F5 is an IgG2b antibody and mouse IgG2b has been shown to promote autoimmunity in the mouse. However, injection of just mouse IgG2b into Lewis rats leads to little binding of antibody in the heart. The binding that does occur is again greatest in the valve region, but dissipates after the first 24 hrs and is virtually negative by 72 hrs. This is significantly different from mAb10F5 which remains significantly bound in this region at the 72 hr time point (p = 7.95E-16, ANOVA). Thus, though IgG2b may have initial autoreactivity in the first 24 hrs, it does not remain bound in the heart valve region. Therefore, mAb10F5 which is associated with the streptococcal conservative M protein sequence demonstrates a more specific reactivity to this region of the heart which may be a factor in the development of valvulitis.