Diagnostic protein expression in human muscle biopsies

Using immunohistochemistry in diagnosing neuromuscular diseases is meant to enhance the diagnostic yield in two ways,The first application aims at vis ualizing molecules which are developmentally, neurally, and/or immunologica lly regulated and not expressed by normal muscle. They are upregulated in p athological conditions and may help assign a given muscular biopsy to one o f the main diagnostic entities (muscular dystrophies, inflammatory myopathy , neurogenic atrophy), In the past, muscle-specific molecules with a define d expression pattern during fetal myogenesis served as antigens, with the r ationale that the developmental program was switched on in new fibers. Rece ntly, myofibers in diseased muscle are thought of as targets of stimuli whi ch are released by macrophages in muscular dystrophy, by lymphocytes in inf lammatory myopathies, or by a lesioned peripheral nerve in neurogenic atrop hies. This has somewhat blurred the borders between the diagnostic groups, for certain molecules, e.g. cytokines, may be upregulated after experimenta l necrotization, denervation, and also in inflammatory myopathies, In the s econd part of this review we summarise the experiences of a Centre in the N orth of England that specialises in the diagnosis and clinical support of p atients with muscular dystrophy. Emphasis is placed on the use of protein e xpression to guide mutation analysis, particularly in the limb-girdle muscu lar dystrophies (a group of diseases that are very difficult to differentia te on clinical grounds alone), We confirm that genetic analysis is essentia l to corroborate the results of protein analysis in certain conditions (par ticularly in calpainopathy). However, we conclude that analysing biopsies f or abnormal protein expression is very useful in aiding the decision betwee n alternative diagnoses.