Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and antisignal recognition particle (SRP) antibodies are frequently associated with immune-mediated necrotizing myopathy (IMNM). However, the difference in clinical manifestations between anti-HMGCR and anti-SRP antibodies is unclear. HMGCR is an essential enzyme for cholesterol biosynthesis and is inhibited by statins that regulate apoptosis of Bcl-2-positive and beta chemokine receptor 4 (CCR4)-positive lymphoma cells. In this study, we aimed to clarify Bcl-2 and CCR4 expressions of lymphocytes in anti-HMGCR antibody-positive IMNM and explore the difference between anti-HMGCR antibody-positive myopathy and other inflammatory myopathies. We retrospectively examined Bcl-2- and CCR4-positive lymphocyte infiltrations in muscle and skin biopsy specimens from 19 anti-HMGCR antibody-positive patients and 75 other idiopathic inflammatory myopathies (IIMs) patients. A higher incidence of Bcl-2- and CCR4-positive lymphocytes was detected in the muscle and skin of anti-HMGCR antibody-positive IMNM patients (p < 0.001). In 5 patients with anti-HMGCR antibodies, Bcl-2-positive lymphocytes formed lymphocytic accumulations, which were not observed in other IIMs. Low-density lipoprotein cholesterol levels were not increased except for patients with Bcl-2-positive lymphocytic accumulations (p = 0.010). Bcl-2 and CCR4 lymphocyte infiltrations could be a pathological characteristic of anti-HMGCR antibody-positive IMNM.
This dual case-control and cohort study assesses for a characteristic pathological hallmark in the muscle tissues of patients with amyotrophic lateral sclerosis.
The patient was a 35-year-old female with an 9-year history of chronic kidney disease awaiting renal transplantation. She was brought to hospital by ambulance due to a generalized convulsive seizure. Her consciousness remained disturbed after treatment for her seizure, and sensorineural deafness was noted. Lactic acid and pyruvic acid levels were extremely elevated in both the plasma and the cerebrospinal fluid, and brain atrophy was obvious on brain imaging. These findings suggested mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes, which was confirmed by muscle biopsy. Previous renal biopsy specimen showed focal segmental glomerulosclerosis and granular swollen epithelial cells. She had no acute progression of the stroke-like episode with L-arginine treatment. However, the brain lesions expanded on MRI. Mitochondrial DNA analysis from a muscle biopsy specimen showed G13513A mutation. The G13513A mutation and the long history of preceding renal failure before the stroke-like episodes were distinctive features in this case.
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