Immunohistochemical and ultrastructural analysis of sporadic inclusion body myositis: a case series

Abstract

Sporadic inclusion body myositis (s-IBM) is a progressive, skeletal muscle disease with poor prognosis. However, establishing the final diagnosis is difficult because of the lack of clear biomarkers in the blood serum and very slow development of clinical symptoms. Moreover, most other organs function normally without any disturbance. Here, in patients with this untreatable disease, we have underlined the importance of immunohistochemical and ultrastructural assessment of skeletal muscle in patients diagnosed with s-IBM. The goal of this study was to identify the distribution of specific antigens and to determine morphological features in order to localize pathological protein aggregates, rimmed vacuoles, and loss of myofibrils, which are key elements in the diagnosis of s-IBM. All studied patients were between 48 and 83 years of age and were hospitalized in the Department of Rheumatology and Internal Medicine between 2011 and 2016. Anamneses revealed an accelerated progression of muscle atrophy, weakness of limb muscles, and difficulties with climbing stairs. Based on histopathology and transmission electron microscopy examination, inflammatory infiltrations consisting of mononuclear cells, severe atrophy and focal necrosis of myofibers, splitting of myofilaments, myelinoid bodies and rimmed vacuoles were observed. Primary antibodies directed against CD3, CD8, CD68, cN1A, beta-amyloid, Tau protein and apolipoprotein B made it possible to identify types of cells within infiltrations as well as the protein deposits within myofibers. Using a combination of immunohistochemistry and electron microscopy methods, we were able to establish the correct final diagnosis and to implement a specific treatment to inhibit disease progression.

Diagnostic Value of Muscle [11C] PIB-PET in Inclusion Body Myositis

“…In IBM, amyloid-beta shows a tendency to accumulate in distal muscles in the present study. In support of this finding, Haczkiewicz et al reported that abnormal pathological findings compatible with s-IBM were detected even in the gastrocnemius muscle of their s-IBM patient, although the presence of amyloid deposition was unclear in the muscle (9).…”

Loss of TDP-43 function and rimmed vacuoles persist after T cell depletion in a xenograft model of sporadic inclusion body myositis

“…A competing hypothesis is that IBM is primarily a degenerative disease, analogous to neurodegenerative diseases. This view is supported by ultrastructural characterization of the inclusions in IBM which form amyloid-like fibrils and tubulofilaments analogous to those observed in the brain in Alzheimer's disease (AD) (16). Indeed, intracellular -amyloid accumulation is observed in IBM muscle, and overexpression of amyloid  precursor protein (APP) in human myoblasts or mouse muscle causes toxicity (17,18).…”

Inclusion body myositis in the rheumatology clinic

“…Muscle biopsy and staining show variation in the fiber size, type II fiber atrophy, endomysial infiltrates, and infiltration of inflammatory infiltrate into non‐necrotic muscle fibers. Immunohistochemistry and Engel's trichrome stain show increased expression of major histocompatibility complex 1 and cytoplasmic red‐rimmed vacuoles, respectively 51 . Electron microscopic studies suggest tubulo‐filamentous inclusions in the cytoplasm, 52 with identification of the contents, location and function using special stains such as TDP43, LC3 and p62 53 .…”

“…Immunohistochemistry and Engel's trichrome stain show increased expression of major histocompatibility complex 1 and cytoplasmic red-rimmed vacuoles, respectively. 51 Electron microscopic studies suggest tubulo-filamentous inclusions in the cytoplasm, 52 with identification of the contents, location and function using special stains such as TDP43, LC3 and p62. 53 Since rimmed vacuoles may not always be present on a muscle biopsy, the higher presence of cyctochrome C oxidase -succinate dehydrogenase + fibers in IBM as compared with polymyositis (PM) or dermatomyositis (DM) may be discriminative, with an area under the curve of 0.93 for diagnosis.…”