CIRCULATING ANTIBODIES AGAINST NICOTINIC ACETYLCHOLINE-RECEPTORS IN CHAGASIC PATIENTS

Human and experimental Chagas' disease causes peripheral nervous syste m damage involving neuromuscular transmission alterations at the neuro muscular junction. Additionally, autoantibodies directed to peripheral nerves and sarcolemmal proteins of skeletal muscle have been describe d. In this work, we analyse the ability of serum immunoglobulin factor s associated with human chagasic infection to bind the affinity-purifi ed nicotinic acetylcholine receptor (nAChR) from electric organs of Di scopyge tschudii and to identify the receptor subunits involved in the interaction. The frequency of serum anti-nAChR reactivity assayed by dot-blot was higher in seropositive chagasic patients than in uninfect ed subjects. Purified IgG obtained from chagasic patients immunoprecip itated a significantly higher fraction of the solubilized nAChR than n ormal IgG. Furthermore, immunoblotting assays indicated that alpha and beta are the main subunits involved in the interaction. Chagasic IgG was able to inhibit the binding of alpha-bungarotoxin to the receptor in a concentration-dependent manner, confirming the contribution of th e alpha-subunit in the autoantibody-receptor interaction. The presence of anti-nAChR antibodies was detected in 73% of chagasic patients wit h impairment of neuromuscular transmission iii conventional electromyo graphical studies, indicating a strong association between seropositiv e reactivity against nAChR and electromyographical abnormalities in ch agasic patients. The chronic binding of these autoantibodies to the nA ChR could induce a decrease in the population of functional nAChRs at the neuromuscular junction and consequently contribute to the electrop hysiological neuromuscular alterations described in the course of chro nic Chagas' disease.