Autoantibodies in Autoimmune Myopathy

Dr. Aggarwal notes, “If you have anti-TIF1-γ antibody, your prognosis is going to be poorer because you have higher likelihood to develop cancer associated dermatomyositis. This risk is much worse in elderly patients.” The antibody is particularly helpful because of its high negative predictive value. Patients with DM who are negative for anti-TIF1-γ have a low probability of occult malignancy.¹⁰

Some researchers argue that the distinction between autoantibodies associated with myositis, myositis-specific autoantibodies and myositis-associated autoantibodies, may not be valuable.
AJPhoto / Science Source

Dr. Gunawardena explains that there are sometimes differences in the ways myositis autoantibodies manifest in juvenile and adult DM. “For example, anti-TIF1-γ in juvenile DM [is associated] with difficult skin disease and ulceration, but not with cancer.”

Anti-Signal Recognition Particle (SRP) Autoantibody
Clinicians should think about anti-SRP autoantibodies in patients with severe, acute myopathy that is difficult to treat. The autoantibody forms against a cytoplasmic ribonucleoprotein called signal recognition particle.^2,3

“Patients with anti-SRP antibody develop very severe muscle weakness [and] very high muscle enzyme levels, and they tend to develop atrophy rather quickly. The prognosis of these patients in terms of disability or muscle strength recovery is poor,” explains Dr. Aggarwal. “However, anti-SRP antibody patients don’t have any extramuscular manifestations, so these patients tend to live longer.”

Because MSAs are specific to IIMs, these autoantibodies can play a role in distinguishing IIMs from inherited or sporadic degenerative myopathies, such as muscular dystrophies.11 Anti-SRP autoantibodies, in particular, are often helpful in this context.²

Anti-SAE Autoantibody & Anti-MJ/NXP2 Autoantibody
Another MSA targets the small ubiquitin-like modifier activating enzyme (SAE). This autoantibody is associated with characteristic skin disease that initially presents without muscle disease. The clinical phenotype often includes systemic features, such as gastrointestinal involvement and dysphagia.³

The anti-MJ/NXP2 autoantibody targets a protein involved in the regulation of cellular senescence. Dr. Gunawardena notes, “The anti-NXP2 subset is associated with calcinosis in both adult and juvenile cases.” The autoantibody is also associated with muscle contractures and severe disease. Some studies have also shown an increased risk of cancer with this autoantibody, although this needs to be further investigated.¹²

High levels of anti-MDA5 despite treatment are a sign of refractory lung disease & increased mortality risk.

FHL-1
The newest myositis autoantibody to be reported is anti-FHL-1 (four-and-a-half LIM domain), an autoantibody against a muscle-specific protein. In contrast, most other MSAs are derived from proteins expressed ubiquitously.

Notably, mutations in the FHL-1 gene are associated with several known X-linked hereditary myopathies. In terms of IIM, this autoantibody is predictive of severe myopathy, dysphagia and vasculitis. The researchers who uncovered this autoantibody used a muscle-specific cDNA library to uncover autoantigens expressed in muscle tissue. Other researchers may use this approach to uncover other potential autoantibody targets in in IIM.¹³

New Classification Scheme for IIMs

A variety of classification schemes for IIMs have been proposed over the years, incorporating a variety of clinical and laboratory findings.¹⁴ Most recently, the International Myositis Classification Criteria Project (IMCCP) has been working with support from both the ACR and the European League of Associations for Rheumatology (EULAR) to define new classification criteria for IIM and its major subgroups.¹⁵ The Boards of EULAR and ACR recently approved this new set of classification criteria for IIMs. These criteria are currently pending publication while they undergo a second round of reviews.