Expression of developmentally regulated cytoskeleton and cell surface proteins in childhood spinal muscular atrophies

Expression of some developmentally regulated cytoskeleton components (desmin, vimentin and myosin heavy chain isoforms) and cell surface proteins (including neural cell adhesion molecule (NCAM), its polysialylated (PSA) isoform and CD24) have been studied by immunohistochemical detection in a series of 23 infantile spinal muscular atrophies (SMA). According to the clinical classification established by Byers and Banker in 1961, 8 cases were type I SMA (Werdnig-Hoffmann's disease), 10 cases were type II (intermediate form), and 5 cases were type III (Kugelberg-Welander's disease). In 15 cases, the percentage of immunoreactive fibers with the various antibodies used has been quantified and the results correlated with clinical data. The aim of the study was to search for variations in the pattern of expression of the proteins to improve the accuracy of diagnosis and prognosis, and to gain an understanding of the pathological processes involved in SMA. The results showed that the pattern of expression of these cytoskeleton and cell surface proteins is abnormal in all types of SMA. However, it was strikingly different in type I and II SMA as opposed to type III. In type I and II SMA, strong NCAM and developmental myosin heavy chain (MHC) expression was observed in atrophic fibers. Numerous atrophic fibers co-expressed desmin and vimentin as well as slow and fast adult MHC. Very few of them expressed PSA NCAM, fetal MHC and CD24. In type III SMA, the number of fibers expressing NCAM, developmental MHC and co-expressing slow and fast adult MHC was low and virtually none of them expressed vimentin or desmin. These findings are in favor of a denervation process occurring very early in life, probably even in utero, in type I and II SMA and leading to a severe impairment of muscle fibers maturation. In contrast, in type III SMA, the process is initiated well after birth and affects mature muscle fibers. In all types of SMA, the ability of muscle fibers to regenerate is low, although some fibers may be reinnervated. Immunohistochemical data was not related to the patients follow-up and thus has no prognostic value.