Inclusion body myositis: from immunopathology and degenerative mechanisms to treatment perspectives

Abstract

Inclusion body myositis is the most common inflammatory myopathy above the age of 50. It becomes clinically apparent around the fourth decade and leads to a slowly, but relentlessly progressive decline in muscular wasting and weakness. The pathology consists of a complex network of inflammatory and degenerative mechanisms, which lead to an attack of muscle fibers by auto-reactive T cells and possibly antibodies. At the same time, various aberrant proteins accumulate within the muscle fibers, including β-amyloid, tau and α-synuclein. Several key components of proinflammatory cell stress mechanisms such as nitric oxide production and macroautophagic processing contribute to the muscle fiber damage. So far, none of the anti-inflammatory or immunomodulatory treatment efforts have been able to halt the disease progression and help the patients. In this summary, the current concept of the complex disease pathology of IBM is reviewed with a focus on recent findings as well as future treatment perspectives.

Keywords::

• autophagy
• inclusion body myositis
• muscle inflammation
• proinflammatory cell stress
• protein accumulation

Financial & competing interests disclosure

J Schmidt has received payments for consultancies or talks, or honoraria, or reimbursements for travel, or research grants from Bayer, Biotest, CSL Behring, Novartis and Octapharma. MCDalakas has received payments for consultancies or talks, or honoraria, or reimbursements for travel, or research grants from CSL Behring, Novartis, Octapharma, Servier, Grifols and Therapath. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • The pathology of inclusion body myositis (IBM) includes inflammatory and degenerative mechanisms and it has been demonstrated in vivo and in vitro that elements of inflammation can trigger or enhance protein accumulation.

• • Insufficient capacity to cope with cell stress and impaired regenerative potential are thought to be crucial elements that, beside certain HLA molecules, may trigger or aggravate the disease course.

• • Dysphagia evolves in approximately two-third of the patients and may be a relevant factor of the disease burden. Dysphagia may even precede the weakness in arms and legs.

• • The diagnosis of IBM relies equally on both, clinical as well as histological criteria and includes the distinctions: i) clinico-pathologically defined IBM; ii) clinically defined IBM; or iii) probable IBM.

• • Whereas standard immunosuppression including glucocorticosteroids is ineffective or even detrimental, a tentatively, temporary course of immunomodulation by intravenous immunoglobulin appears to be justified in selected patients, especially those with swallowing problems as demonstrated by a controlled study [60]

• • Standardized evaluation of patients and identification of suitable outcome measures will be pivotal for the design of future treatment strategies.

• • Future trials should aim to test molecules that block inflammation, cell stress as well as degeneration and, at the same time, promote muscle regeneration.

Notes