New Tools for Myositis Diagnosis, Classification & Management

Anti-NT5C1a in IBM

Early immunohistochemical studies suggested qB cells are sparse in the muscles of IBM patients.³⁵ However, more recent evidence shows that in gene expression profiling, immunoglobulin transcripts are abundant in their muscles, including the antibody-producing CD138+ plasma cells.³⁶

“Where there are plasma cells and immunoglobulin transcripts, you expect to find an autoantibody,” said Dr. Mammen. Researchers identified an autoantibody, cytosolic 5’ nucleotidase 1A (NT5C1a), in patients with IBM. “This protein is abundant in skeletal muscle—it catalyzes nucleotide hydrolysis to nucleosides—but its function in muscle is not well understood.” Anti-NT5C1a is localized within rimmed vacuoles or around perinuclear areas of the IBM muscle.³⁷ Patients with IBM who have NT5C1a antibodies tend to have more severe disease.³⁸

Dr. Mammen proposed a speculative model of IBM pathogenesis based on genetic susceptibility toward autophagy and a strong autoimmune component.

“Maybe some patients with IBM have this genetic susceptibility to a myodegenerative process. Maybe this FYCO1 variant makes them less able to handle misfolded proteins. As the patients age, they have abnormal protein accumulation that causes damage to the muscle and cellular stress, which causes more abnormal protein accumulation,” he said. “Then, I could imagine that the damage to the muscle in patients who have the right immunogenetic predisposition—they’re male, maybe they have the right environmental triggers—these things come together and cause the initiation of autoimmunity.” Autoreactive T cells and autoantibodies come back to do more muscle damage, he said.

There are no approved treatments for IBM and most clinicians don’t believe immunosuppression has a significant sustained effect, so resist the urge to use immunosuppressants in these patients, said Dr. Mammen. “We need to develop drugs to deplete aggressive CD57+ and cytotoxic T cells.”

Exercise, such as low-impact aerobics, stretching and endurance exercises,
and physical therapy are helpful recom­mendations for these patients, he concluded. He recommended foot to ankle orthotics for patients with foot drop and training family members in the Heimlich maneuver to intervene when patients experience dysphagia.

Susan Bernstein is a freelance journalist based in Atlanta.

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