VGKC (voltage-gated potassium channel) antibodies

VGKC-complex antibodies were first discovered between 1995 and 2001 in various clinical syndromes, such as limbic encephalitis, Morvan’s syndrome or neuromyotonia. Over the past few years however it was found, that the “VGKC-complex” comprises three antigens, the antibodies to the different antigens having different characteristics and clinical relevance:

  1. Antibodies against LGI1
  2. Antibodies against CASPR2
  3. Antibodies against other antigens

Antibodies against LGI1 and CASPR2 bind to extracellular domains of potassium-channel-associated proteins and are therefore typical antibodies against surface antigens. They have pathogenic relevance and correlate with specific clinical pictures.

LGI1 – Limbic encephalitis, FBDS, hyponatremia
CASPR2 – Limbic encephalitis, neuromyotonia, Morvan’s syndrome, neuropathic pain

LGI1 and CASPR2-associated syndromes respond well to immunotherapy. CASPR2 antibodies can be associated with tumors (thymomas).

In contrast, VGKC-complex antibodies not directed against LGI1 and CASPR2 have no clinical relevance in the initial diagnostics. These antibodies are directed against intracellular components of the VGKC-complex or even against the 125J-α-dendrotoxin used for the marking of VGKC-complexes in the test. They are associated with heterogenic clinical syndromes, without definite indication of an autoimmune genesis and can also be found in 5 % of control persons (1).

Testing for VGKC-complex antibodies is also not suitable as a sole screening test for the demonstration of LGI1 or CASPR2 antibodies, as this method is not sensitive enough. Low-titer LGI1 and CASPR2 results are not captured (2).

The diagnostics for LGI1 antibodies and CASPR2 antibodies are part of the standard program for neural antibodies at Labor Krone.

1. Lang B, et al. J Neurol Neurosurg  Psychiatry. 2017 Apr;88(4):353-361
2. van Sonderen et al., Neurology. 2016 May 3; 86:1692-1699