4. Autoantibodies: Patient test assays
How to efficiently detect autoantibodies?
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We perform most of the neuroimmunology tests in Norway. For the detection of onconeural antibodies we use line blots and immunohistochemical analyses of cerebellar tissue. Currently, we are able to test 11 different antibodies related to paraneoplastic neurological syndromes (PNS). These are mainly antibodies causing ataxia by targeting the neuronal population of the cerebellum (Medusa head ataxia).
Three groups of autoantibodies can be delineated according to the neuronal localization of the targeted antigen:
Group 1: Nuclear and cytoplasmic neuronal antigens (NCNA)
- Anti-Hu [ANNA-1]
- Anti-Ri [ANNA-2]
- Anti-Yo [PCCA-1]
- Anti-Ma1/2 [PNMA-1/2]
- Anti-CV2/CRMP5
- Anti-Sox1 [AGNA]
- Anti-Zic4
- Anti-Gephyrin
- Anti-GABARAP
All these antibodies, except GABARAP, are associated with PNS and their frequency is rare: a European study conducted during 8 years was able to compile less than 1000 cases and incidence is estimated being about 0.01 % of all cancers. [PMID:20212230; DOI: 10.1001/archneurol.2009.341]
Group 2: Cell-surface synaptic antigens (CSSA)
- Anti-NMDAR
- Anti-Lgi1
- Anti-Caspr2
- Anti-GABABR
- Anti-AMPAR
- Anti- VGCC
- Anti-GlycineR
- Anti-Tr/DNER
- Anti-mGluR1
- Anti-mGluR5.
Patients with CSSA-Abs share common features: (I) symptoms seem to be related to the disruption of the target antigen by the antibodies; (II) symptoms can be reversed by immunotherapy more commonly than in patients with NCNA-Abs; (III) the association with malignancy is much less consistent; (IV) neurological symptoms are similar to a pharmacological blockade of the recognized antigen.
Group 3: Intracellular synaptic antigens (ISA)
- Anti-GAD65
- Anti-Amphiphysin
Both ISA targeted antigens are located in the presynaptic terminal of neurons, a region where antibodies can reach cytoplasmic proteins. Moreover, immune response seems to imply both cellular and humeral compounds.
Viaccoz, A. & Honnorat, J. Curr Treat Options Neurol (2013) 15: 150. doi:10.1007/s11940-013-0220-2
A new approach is that we are looking at exosomes which are small, extracellular vesicles released by cells in the body. These contain various molecules including proteins, lipids and RNA. Cancer cells release exosomes which promotes growth and metastasis of the tumour, as well as suppresses the immune system. As exosomes circulate in the blood, they serve as a promising source of new biomarkers of disease. We are analysing the RNA content of serum exosomes from patients with ovarian cancer and PCD to identify new biomarkers which can help improve diagnosis of PCD.
Click on the images below to learn more about the onconeural antibodies we analyze in our lab.