Autoantibodies Produced at the Site of Tissue Damage Provide Evidence of Humoral Autoimmunity in Inclusion Body Myositis

Inclusion body myositis (IBM) belongs to a group of muscle diseases known as the inflammatory myopathies. The presence of antibody-secreting plasma cells in IBM muscle implicates the humoral immune response in this disease. However, whether the humoral immune response actively contributes to IBM pathology has not been established. We sought to investigate whether the humoral immune response in IBM both in the periphery and at the site of tissue damage was directed towards self-antigens. Peripheral autoantibodies present in IBM serum but not control serum recognized self-antigens in both muscle tissue and human-derived cell lines. To study the humoral immune response at the site of tissue damage in IBM patients, we isolated single plasma cells directly from IBM-derived muscle tissue sections and from these cells, reconstructed a series of recombinant immunoglobulins (rIgG). These rIgG, each representing a single muscle-associated plasma cell, were examined for reactivity to self-antigens. Both, flow cytometry and immunoblotting revealed that these rIgG recognized antigens expressed by cell lines and in muscle tissue homogenates. Using a mass spectrometry-based approach, Desmin, a major intermediate filament protein, expressed abundantly in muscle tissue, was identified as the target of one IBM muscle-derived rIgG. Collectively, these data support the view that IBM includes a humoral immune response in both the periphery and at the site of tissue damage that is directed towards self-antigens

Effects of group size on the threat-sensitive response to varying concentrations of chemical alarm cues by juvenile convict cichlids

The threat-sensitive predator avoidance model predicts that prey should balance the intensity of antipredator responses against perceived predation risk, resulting in a graded response pattern. Recent studies have demonstrated considerable interspecific variation in the intensity of threat-sensitive response patterns, ranging from strongly graded to relatively nongraded or "hypersensitive" threat-sensitive response patterns. Here, we test for intraspecific plasticity in threat-sensitive responses by varying group size. We exposed juvenile convict cichlids, Archocentrus nigrofasciatus (Günther, 1867), as individuals or in small (groups of three) or large (groups of six) shoals to a series of dilutions of conspecific chemical alarm cues and a distilled water control. Singleton cichlids exhibited significant reductions in time spent moving and in frequency of foraging attempts (relative to distilled water controls) when exposed to a 12.5% dilution of conspecific alarm cue, with no difference in response intensity at higher stimulus concentrations, suggesting a nongraded (hypersensitive) response pattern. Small shoals exhibited a similar response pattern, but at a higher response threshold (25% dilution of stock alarm cue solution). Large shoals, however, exhibited a graded response pattern. These results suggest that group size influences the trade-off between predator avoidance and other fitness related activities, resulting in flexible threat-sensitive response patterns