Presence of antibodies against the third intracellular loop of the m2 muscarinic receptor in the sera of chronic chagasic patients

Patients in the chronic phase of Chagas' disease suffer from a slowly evolv ing inflammatory cardiomyopathy that can lead to severe cardiac dilatation, congestive heart failure, and death. This process appears to be caused by autoimmune recognition of heart tissue by a mononuclear cell infiltrate dec ades after infection with the parasite Trypanosoma cruzi, Recent evidence s uggests that there are circulating antibodies in chronic chagasic patients that alter the physiological behavior of the heart on binding to G-protein- coupled cardiovascular receptors, including beta 1-adrenergic and m2 muscar inic receptors, A 42 kDa fusion protein was constructed that contains the c entral part of the third intracellular loop (i3; Arg(267)-Arg(381)) of the human m2 muscarinic receptor, linked to glutathione S-transferase, This fus ion protein was overexpressed in Escherichia coli and subsequently purified by affinity chromatography, Based on Western blots, the i3 loop is specifi cally recognized by the sera of chronic chagasic patients who have reached advanced stages of cardiac failure (according to the Los Andes classificati on). Analysis of the prevalence and distribution of these antibodies shows a strong association between seropositive patients and moderate (group II) to severe (group III) heart dysfunction.-Retondaro, F. C., dos Santos Costa , P. C., Pedrosa, R. C., Kurtenbach, E. Presence of antibodies against the third intracellular loop of the m2 muscarinic receptor in the sera of chron ic chagasic patients.