Lab discoveries fuel updates for autoimmune movement disorders test

Eye on Innovation

In a world of ever-faster technical change, Mayo Clinic Laboratories is uniquely positioned to innovate. Collaboration with clinicians pinpoints unmet patient needs and facilitates the development of diagnostic testing that provides answers.

Although generally treatable, autoimmune movement disorders are often overlooked in clinical practice. The resulting misdiagnosis can delay patient treatment and lead to severe, permanent disability.

Diagnosis is challenging because these conditions are associated with a complex spectrum of biomarkers, symptoms and treatments. In some cases, the autoimmune response is paraneoplastic — triggered by an underlying cancerous tumor. What's more, autoimmune neurology is evolving rapidly, as new antibodies are identified.

Mayo Clinic Laboratories is a world leader in autoimmune neurology testing. Antibodies discovered in Mayo Clinic's Clinical Neuroimmunology Laboratory and elsewhere are validated and incorporated into the laboratories’ phenotype-specific assays to provide actionable information for clinicians.

The latest innovation adds four recently identified biomarkers to Mayo Clinic Laboratories autoimmune movement disorders test (Mayo IDs: MDS2 (serum) and MDC2 (CSF)). All four antibodies have been shown to respond to immunotherapy.

“This launch is exciting because it broadens the repertoire of biomarkers available for evaluating patients with autoimmune movement disorders,” says Andrew McKeon, M.B., B.Ch., M.D., a neurologist and director of Mayo Clinic’s neuroimmunology laboratory. “The expanded test will help clinicians to identify an autoimmune disorder and to determine if a patient’s disorder is likely paraneoplastic. As we learn more about these conditions, we are translating those advances into better testing for better patient care.”

Andrew McKeon, M.B., B.Ch., M.D.

Digging for antibody clues

Autoimmune movement disorder is an umbrella term that covers conditions such as ataxia, chorea, myoclonus, and dystonia. Symptoms include a sudden speeding up or slowing down of a person’s body movements, resulting in uncontrollable muscle jerks or problems with balance.

The disorders occur when the body’s immune system, which is meant to fight infections, suddenly attacks the brain. Once discovered, movement disorders can often be treated with immunotherapy that lessens or halts the attacks. However, delays in treatment can lead to permanent loss of function.

Antibodies are vital clues for precise diagnosis. “Identifying antibodies is important not only to establishing an autoimmune diagnosis but also to informing what type of movement disorder is present and what to potentially expect from treatment,” Dr. McKeon says.

In 2018, Mayo Clinic Laboratories launched an autoimmune movement disorders evaluation that covered 20 antibodies associated with these conditions. Adding the four new antibodies — septin-5, septin-7, adaptor protein-3B2, and neurochondrin — reflects Mayo Clinic Laboratories commitment to providing the most up-to-date testing available.

These test development efforts benefit from collaboration with Mayo Clinic clinician-researchers. As a subspecialist in autoimmune neurology, Dr. McKeon has experience with the diagnosis and treatment of autoimmune movement disorders.

“I spend approximately 35% of my time seeing patients and the rest of my time working in the neuroimmunology lab, either doing clinical service, new test development, or research into new biomarkers for autoimmune diseases,” he says.

Two of the new antibodies — septin-5 and septin-7 — were discovered in Mayo Clinic’s neuroimmunology laboratory. The symbiosis between patient care and research allows Mayo Clinic to elucidate the phenotypes associated with newly identified antibodies.

“Septin-5 is encountered in patients with ataxia and prominent eye movement disorders,” Dr. McKeon says. “Septin-7 is a broader phenotype. Encephalopathy with prominent neuropsychiatric features is most common.”

Another of the new antibodies — adaptor protein-3B2 — was “rediscovered” at Mayo Clinic after first being reported by another center more than 25 years ago. “But the report was just a single case that was kind of lost in the literature,” Dr. McKeon says.

Researchers in Mayo Clinic’s neuroimmunology laboratory subsequently identified in 10 patients what they thought was an unclassified antibody. After reviewing medical literature, the researchers found the old report and realized the antibody they had identified was adaptor protein-3B2.

“The common theme in patients with this antibody is gait disorders,” Dr. McKeon says. Neuorchondrin is associated with brainstem encephalitis.

Mayo Clinic Laboratories autoimmune movement disorders assay also includes kelch-like protein 11 (KLHL11). The groundbreaking discovery that KLHL11 autoantibodies cause testicular cancer-associated paraneoplastic encephalitis was made by a research team that included Mayo Clinic scientists.

Targeted testing

Mayo Clinic Laboratories phenotype-specific approach requires careful decision making about which antibodies to include in testing. Truly innovative evaluations must be comprehensive yet efficient. Meeting that goal for the testing of autoimmune movement disorders requires a relatively long list of antibodies.

“The reality is that these disorders are associated with a lot of antibody biomarkers. And very often, there’s an overlap in these disorders,” Dr. McKeon says. “Rather than splitting our evaluation up into very specific syndromes, we have kept it to one evaluation that is pertinent to diverse movement disorders.”

Equally important is deciding which antibodies to exclude.

“It’s not a catchall approach, with all autoimmune neurology antibodies thrown into a single evaluation,” Dr. McKeon says. “Antibodies such as aquaporin-4 and myelin oligodendrocyte glycoprotein, or MOG, typically indicate other autoimmune neurological disorders. Those antibodies aren’t included in the movement disorders test, which helps to improve that test’s specificity and sensitivity.”

Similarly, the movement disorders test doesn’t cover glycine receptor antibody. That antibody is one of just four antibodies associated with stiff-person syndrome — an autoimmune movement disorder with a distinctive phenotype.

Mayo Clinic Laboratories stiff-person spectrum disorders evaluation (TEST ID: SPPC / SPPS) covers those four antibodies. Glycine receptor evaluation is also available as a standalone test in serum (TEST ID: GLYCS) or cerebral spinal fluid (TEST ID: GLYCC).

“Our phenotype-specific evaluations are designed with the understanding that it’s really important for clinicians to drill down on the phenotype and establish the trajectory of a patient’s illness before ordering testing,” Dr. McKeon says. “Autoimmune movement disorders is a complex field, and we’re making new discoveries all the time. It’s gratifying to now have validated tests that translate these discoveries to patient care.”

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Cory Pedersen

Cory Pedersen is a senior marketing specialist for Mayo Clinic Laboratories.