P5.30 Inclusion body myositis: A diagnostic challenge

Abstract

The currently accepted diagnostic criteria for inclusion body myositis (IBM), first published in 1995, comprise pathological and clinical elements. The pathological features being endomysial inflammation with invasion of intact fibres, rimmed vacuoles and either amyloid or tubulofilamentous inclusions; all of these must be present for a definite diagnosis. However, these features are not specific to IBM and furthermore in many clinically typical cases one or more may be absent. Recently a variety of proteins more commonly associated with neurodegenerative diseases have been found to accumulate in muscle fibres in IBM. The benefit of immunohistochemical staining for these proteins in the diagnosis of IBM is unknown. We propose that these protein accumulations may assist in the diagnosis of IBM and help in differentiating it from other myopathies. To identify the most sensitive immunohistochemical techniques available to UK diagnostic pathology laboratories of detecting such protein inclusions and to determine their sensitivity and specificity for the diagnosis of IBM. We identified 6 cases of pathologically definite IBM according to the current criteria and 6 normal control cases. All cases had been assessed clinically and had undergone a biopsy at the National Hospital for Neurology and Neurosurgery, Queen Square, London. A number of neurodegenerative proteins and inflammatory markers were identified that may be of diagnostic significance. Antibodies to these proteins were optimised using control tissue known to contain the protein of interest. Protein inclusions found in IBM were labelled with an antibody to p62, an adapter protein which binds ubiquitin and regulates signalling cascades through ubiquitination. These inclusions were not found in the normal controls. Further work to quantify the abnormalities in IBM and disease controls will be undertaken before any of these markers can be recommended for diagnostic use.