Advancing the search for KLHL11 protein biomarkers

Precision testing for testicular cancer-associated paraneoplastic encephalitis

The intersection of Mayo Clinic’s research and clinical practice and the Neuroimmunology Laboratory allowed for the implementation of the world’s first evidence-based test to confirm the presence of Kelch-like Protein 11 (KLHL11) autoantibodies, which are linked to a rare form of paraneoplastic encephalitis.

The groundbreaking discovery that testicular cancer-associated paraneoplastic encephalitis is caused by KLHL11 autoantibodies — by a team of researchers that included Mayo Clinic scientists — paved the way for development of the assay. The innovative test first screens patients for KLHL11 proteins through a mechanized, cell-based assay that utilizes cutting-edge, slide-scanner technology, then employs tissue immunofluorescence to confirm presence of the protein, which exudes a unique "sparkles" pattern.

Altering outcomes with early detection

Testicular cancer-associated paraneoplastic encephalitis is often misdiagnosed due to neurological syndrome symptoms preceding tumor detection. Identification of KLHL11 autoantibodies, which seems to be one of the most common paraneoplastic antibodies in men, enables providers to offer specific treatment protocols, such as cancer treatments and immunosuppressive therapies, to manage and treat the disease. Early and accurate diagnosis of this syndrome is critical for disease stabilization and possible reversal.

By the numbers


70%

association with testicular cancer2


2.8

cases per 100,000 men1


58%

of patients stabilized neurologically or improved upon correct diagnosis2

When to consider testing

Consider KLHL11 testing for all patients presenting with testicular tumors and one or more of the following:

  • Hearing loss or tinnitus
  • Double vision
  • Slurred speech
  • Difficulty swallowing
  • Vertigo
  • Impaired coordination
  • Difficulty walking
  • Brainstem or cerebellar syndromes

Which test should I order?


A Test in Focus

Divyanshu (Div) Dubey, M.B.B.S., explains how Mayo Clinic Labs’ new Kelch-11 antibody test — the first in the world — can confirm diagnosis, guide treatment, and improve outcomes in patients affected by testicular cancer-associated paraneoplastic encephalitis.

Learn more about how to order this evaluation at your institution.

Additional resources

Publications and articles

Mayo Clinic autoimmune neurologists Sean Pittock, M.D., and Divyanshu Dubey, M.B.B.S.  discuss the discovery of the protein biomarker behind testicular cancer-associated paraneoplastic encephalitis. Read the journal article detailing the features of testicular cancer-associated paraneoplastic encephalitis linked to KLHL11 autoantibodies.

1 Mandel-Brehm C, Dubey D, Kryzer TJ, et al. Kelch-like Protein 11 Antibodies in Seminoma-Associated Paraneoplastic Encephalitis. N Engl J Med. 2019; 381:47-54.

2Dubey D, Wilson MR, Clarkson B, et al. Expanded Clinical Phenotype, Oncological Associations,and Immunopathologic Insights of ParaneoplasticKelch-like Protein-11 Encephalitis. JAMA Neurol. 2020 Aug 3; 77(11):1-10.