Motor neuron reactivity of sera from animals with autoimmune models of motor neuron destruction
Amyotrophic Lateral Sclerosis
To determine whether mammalian upper and lower motoneurons share common epitopes, we assessed the immunohistochemical reactivity of serum IgG of two animal models, experimental autoimmune motor neuron disease with destruction of lower motoneurons (EAMND) and experimental autoimmune gray matter disease with destruction of both lower and upper motoneurons (EAGMD). EAMND serum IgG reacted with the cytoplasm of guinea pig spinal motoneurons in a patchy granular pattern paralleling the in vivo localization in the guinea pig model. The EAMND serum IgG also reacted with human upper and lower motoneurons. EAGMD serum IgG reacted with the cytoplasm and subsequently the external membranes of upper and lower motoneurons of guinea pig and human tissues, also paralleling the in vivo localization. IgG was detected in ipsilateral ventral horn following hind limb injections of EAMND and EAGMD serum, thereby suggesting retrograde transport to the motoneuron cell body. The presence of shared epitopes in upper and lower human motoneurons, and the ability of IgG to reach the motoneuron cell body by retrograde transport from the periphery provides evidence for the potential role of autoimmune mechanisms in motoneuron diseases.