Antibody deposition in the stria vascularis of the MRL-Fas lpr mouse

Abstract

The MRL-Fas lpr mouse, a model of multisystemic, organ non-specific autoimmune disease, has been proposed as a model of immune-mediated inner ear disease. Preliminary studies indicate that it develops cochlear pathology focused in the stria vascularis including intracellular edema and degeneration which develops in the absence of an inflammatory infiltrate but in the presence of antibody deposition. It was thus hypothesized that the antibodies found in the stria were mediating a direct pathologic effect on this structure, without recruiting classical inflammatory mediators. It was further hypothesized that the antibodies deposited within the stria would be derived from the non-complement fixing isotypes and subclasses, which are known to be able to mediate direct pathologic effects on target tissues. This study utilized immunohistologic techniques to identify the antibody isotypes and subclasses deposited within the stria vascularis of the MRL-Fas lpr mouse. Results indicate that all antibody isotypes and subclasses can be identified within the stria vascularis in the absence of complement. Thus, antibody deposition was not restricted to non-complement fixing antibodies. While it is possible that antibodies are mediating direct pathologic effects within the stria, the non-specific nature of the antibody deposition may indicate that these antibodies are not responsible for the observed pathology. Rather, other mechanisms, such as metabolic and genetic etiologies, must also be considered.