'Medusa head ataxia': the expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 3: Anti-Yo/CDR2, anti-Nb/AP3B2, PCA-2, anti-Tr/DNER, other antibodies, diagnostic pitfalls, summary and outlook

J Neuroinflammation. 2015 Sep 17:12:168. doi: 10.1186/s12974-015-0358-9.

Abstract

Serological testing for anti-neural autoantibodies is important in patients presenting with idiopathic cerebellar ataxia, since these autoantibodies may indicate cancer, determine treatment and predict prognosis. While some of them target nuclear antigens present in all or most CNS neurons (e.g. anti-Hu, anti-Ri), others more specifically target antigens present in the cytoplasm or plasma membrane of Purkinje cells (PC). In this series of articles, we provide a detailed review of the clinical and paraclinical features, oncological, therapeutic and prognostic implications, pathogenetic relevance, and differential laboratory diagnosis of the 12 most common PC autoantibodies (often referred to as 'Medusa head antibodies' due to their characteristic somatodendritic binding pattern when tested by immunohistochemistry). To assist immunologists and neurologists in diagnosing these disorders, typical high-resolution immunohistochemical images of all 12 reactivities are presented, diagnostic pitfalls discussed and all currently available assays reviewed. Of note, most of these antibodies target antigens involved in the mGluR1/calcium pathway essential for PC function and survival. Many of the antigens also play a role in spinocerebellar ataxia. Part 1 focuses on anti-metabotropic glutamate receptor 1-, anti-Homer protein homolog 3-, anti-Sj/inositol 1,4,5-trisphosphate receptor- and anti-carbonic anhydrase-related protein VIII-associated autoimmune cerebellar ataxia (ACA); part 2 covers anti-protein kinase C gamma-, anti-glutamate receptor delta-2-, anti-Ca/RhoGTPase-activating protein 26- and anti-voltage-gated calcium channel-associated ACA; and part 3 reviews the current knowledge on anti-Tr/delta notch-like epidermal growth factor-related receptor-, anti-Nb/AP3B2-, anti-Yo/cerebellar degeneration-related protein 2- and Purkinje cell antibody 2-associated ACA, discusses differential diagnostic aspects and provides a summary and outlook.

Publication types

  • Review

MeSH terms

  • Adaptor Protein Complex 3 / immunology*
  • Adaptor Protein Complex beta Subunits / immunology*
  • Autoantibodies / metabolism*
  • Cerebellar Ataxia* / diagnosis
  • Cerebellar Ataxia* / immunology
  • Cerebellar Ataxia* / metabolism
  • Humans
  • Nerve Tissue Proteins / immunology*
  • Purkinje Cells
  • Receptors, Cell Surface / immunology*

Substances

  • AP3B2 protein, human
  • Adaptor Protein Complex 3
  • Adaptor Protein Complex beta Subunits
  • Autoantibodies
  • CDR2 protein, human
  • DNER protein, human
  • Nerve Tissue Proteins
  • Purkinje cell protein L7
  • Receptors, Cell Surface