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

'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

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Review

'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

S Jarius et al. J Neuroinflammation. .

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.

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Figures

Fig. 1
Fig. 1
Expression of CDR2 in the human cerebellum as demonstrated by IHC (modified image from the Human Protein Atlas image database [33])
Fig. 2
Fig. 2
Binding of anti-Yo (PCA-1) from a patient with ACA to a mouse cerebellum tissue section. The patient antibody was detected by use of a goat anti-human IgG secondary antibody labelled with Alexa Fluor@488 (green)
Fig. 3
Fig. 3
Expression of AP3B2 in the human cerebellum as demonstrated by IHC (modified image from the Human Protein Atlas image database [33])
Fig. 4
Fig. 4
Binding of PCA-2-IgG from a patient with ACA to a formalin-fixed mouse cerebellum tissue section. Note the additional staining of the cytoplasm of cerebellar granular cells (so-called ‘chicken-wire pattern’). A FITC-labelled anti-human IgG secondary antibody was used to visualize bound patient IgG. Image modified from Vernino S and Lennon VA. New Purkinje cell antibody (PCA-2): marker of lung cancer-related neurological autoimmunity. Ann Neurol 2000, 47:297-305; © 2000 by the American Neurological Association; reprinted with kind permission from the publisher
Fig. 5
Fig. 5
Expression of DNER in the human cerebellum as demonstrated by IHC (modified image from the Human Protein Atlas image database [33])
Fig. 6
Fig. 6
Binding of IgG from a patient with anti-Tr/DNER-associated ACA to a rat cerebellum tissue section. A goat anti-human IgG secondary antibody labelled with fluorescein isothiocyanate (green fluorescence) was used to visualize bound patient IgG
Fig. 7
Fig. 7
IHC patterns strongly depend on sectional planes and tissue donor species. a, b Binding of a commercial Homer-3 antibody to different sectional planes of human cerebellum tissue (modified images from [33]). c, d Binding of human IgG from a patient with ITPR1-Ab-positive ACA to mouse (c) and monkey (d) PC dendrites, respectively, sectioned at different planes. e, f Anti-Yo IgG antibodies as detected by use of primate (e) and mouse (f) cerebellum tissue sections, respectively, sectioned at different planes

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References

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