Dados do Trabalho

Título

FHL1-related myopathy is associated to inflammatory findings in skeletal muscle histology.

Resumo

INTRODUCTION: FHL1 (Four-and-a-Half-LIM domains 1) is a protein involved in signaling processes, differentiation and maintenance of structural cellular elements. Mutations in FHL1 can lead to a myopathy with myofibrillar derangement and intracytoplasmic bodies, known as reducing body myopathy (RBM). RBM is characterized by progressive weakness in childhood and the presence of cytoplasmic aggregates that reduce nitro-blue-tetrazolium (NBT) in muscle fibers. In addition to RBM, other phenotypes are described, such as Emery-Dreifuss, X-linked scapuloperoneal myopathy and hypertrophic cardiomyopathy. We recently described a case of RBM presenting as inflammatory myopathy. However, there is no data systematically investigating inflammatory findings in muscle biopsy in FHL1-related myopathy.

OBJECTIVE: To evaluate inflammatory findings in skeletal muscle histology of patients with FHL1-related myopathy.

METHOD: We retrospectively identified patients with FHL1-related myopathy in a tertiary neuromuscular center. We reviewed medical records to clinical description. We evaluate histopathological findings of muscle biopsy of the patients using the following stains: hematoxylin and eosin, modified Gömöri's trichrome, NADH-tetrazolium reductase, succinate dehydrogenase, cytochrome-c-oxidase, acid phosphatase, NBT and immunohistochemistry using commercial antibodies against desmin, CD4, CD8, CD68 and major histocompatibility complex type I (MHC-I).

RESULTS: Five patients with FHL1-related myopathy were clinically evaluated. Two patients (one male and one female) presented the classical RBM phenotype, and three females presented an X-linked scapuloperoneal myopathy. All patients presented increased serum CK over 10x the UNL. Histopathological analysis from all patients showed intracytoplasmic desmin-positive aggregates, NBT-reducing bodies, necrotic fibers and intense increased acid phosphatase activity. Moderate endomysial CD4+, CD68+ cell infiltrates, in addition to milder CD8+ infiltrates, with mild to moderate increase in MHC-I staining was observed in all patients.

CONCLUSION: FHL1-related myopathy is associated with intense inflammatory findings in skeletal muscle histology. Some cases can be misdiagnosed as inflammatory myopathy. Curiously, anti-FHL1 antibodies was previously described in 25% of patients with idiopathic inflammatory myopathy, which indicate that FHL1 can be an epitope able to induce an inflammatory response.

Palavras Chave

FHL1; myofibrillar myopathy; inflammatory myopathy; reducing body myopathy.

Área

Doenças Neuromusculares