Thesis defense Anke Rietveld (Donders series 497)

26 April 2021

Promotors: prof. B. van Engelen and prof. G. Pruijn
Co-promotor: dr. C. Saris

Anti-cytosolic 5’-nucleotidase 1A autoantibodies in inclusion body myositis, clinical application and molecular correlations

Inclusion body myositis (IBM) is a myopathy occurring in patients over 45 years, leading to progressive weakness of the upper legs, hands and swallowing muscles. The diagnosis can be difficult and the cause of the disease is yet unknown.

In 2011, two research groups independently discovered the autoantibody anti-cN-1A in IBM patients. The detection of autoantibodies in other forms of myositis has improved the diagnostic process and it has allowed correlations of serotype with a specific phenotype and prognosis. The presence of anti-cN-1A autoantibodies in IBM does not only allow amelioration of the diagnostic and observations on correlations between pheno- and serotype, but it sheds also more light on the pathophysiological process underlying the disease.

In the current research, the autoantibody was found in other autoimmune diseases, but not in other forms of myositis. Anti-cN-1A autoantibody testing can thus be part of the diagnostic procedures if IBM is suspected.

We have studied a big international cohort of IBM patient, revealing that IBM patients with anti-cN-1A autoantibodies have a more typical pattern of muscle weakness and a worse prognosis. The prognosis is not explained by worse dysphagia; swallowing tests and muscle ultrasound of the swallowing muscles shows similar results in our small cohort of anti-cN-1A positive and negative IBM patients.

The cN-1A protein that is attacked by anti-cN-1A autoantibodies is equally expressed in IBM and healthy muscle tissue, so we cannot explain the autoimmune reaction by a higher expression of the protein in IBM.