Investigations of caspr2, an autoantigen of encephalitis and neuromyotonia

Abstract

Objective-To report clinical and immunological investigations of contactin-associated proteinlike 2 (Caspr2), an autoantigen of encephalitis and peripheral nerve hyperexcitability (PNH) previously attributed to voltage-gated potassium channels (VGKC).Methods-Clinical analysis of patients with encephalitis, PNH, or both. Immunoprecipitation and mass spectrometry were used to identify the antigen and to develop an assay with Caspr2-expressing cells. Immunoabsorption with Caspr2 and comparative immunostaining of brain and peripheral nerve of wild-type and Caspr2-null mice were used to assess antibody specificity.

The Emerging Link Between Autoimmune Disorders and Neuropsychiatric Disease

“…Autoantibodies recognizing Caspr2 have been described in autoimmune encephalitis, often in association with symptoms of peripheral nerve hyperexcitabilty such as neuromyotonia (difficulty in muscle relaxation), cramps, fasciculations, and muscle spasms (Table 1). 30,33,39 Taken together, these two autoimmune syndromes highlight the role of synaptic organizers in autoimmune encephalitis and open new avenues toward understanding the role of trans -synaptic signals in disease states.…”

Antibodies against cell adhesion molecules and neural structures in paraneoplastic neuropathies

“…This patient had a thymoma and presented with a sensory‐motor rapidly progressing chronic polyradiculoneuropathy with demyelinating features in the EMG, fulfilling diagnostic criteria of CIDP. This patient did not show any evidence of neuromyotonia (frequently associated with anti‐CASPR2 antibodies and thymoma26) and also reacted against DRG neurons and Schwann cells.…”

“…Sera were tested for antibodies against previously described antigens at the node of Ranvier; CNTN1,10 neurofascin 140 (NF140),24 neurofascin 155 (NF155),25 neurofascin 186 (NF186),24 contactin‐associated protein 2 (CASPR‐2)26, and the CNTN1/contactin‐associated protein 1 (CASPR1) complex10; and against other neural cell adhesion molecules (L1CAM and NCAM1). Sera were additionally screened for novel IgM and IgG reactivities against primary cultures of rat peripheral nerve components: dorsal root ganglia (DRG) neurons, motor neurons, and Schwann cells.…”

Immune Mediated Diseases and Immune Modulation in the Neurocritical Care Unit

“…More recently, however, limbic encephalitis has been recognized to occur in patients without cancer and a variety of pathologic antigenic targets have been identified. Antibodies to voltage-gated potassium channels (VGKCs) were identified in a number of patients with non-paraneoplastic limbic encephalitis, but further studies have shown that the real antigens in these patients are leucine-rich glioma inactivated 1, contactinassociated protein-like 2, and contactin-2, all of which are associated with VGKCs [230,231]. The spectrum of autoantigens associated with in limbic encephalitis, however, continues to expand, and now includes the N-methyl-D-aspartate receptor (NMDAR), the AMPA receptor, the GABA = gamma-aminobutyric acid receptor, and glutamic acid decarboxylase [232][233][234][235].…”

“…The phenotype of the disorder caused by VGKCs appears to be related to the component of the K + channel to which the antibody is directed. For instance, antibodies to contactinassociated protein-2 tend to be associated with limbic encephalitis, Morvan's syndrome, and Issac's syndrome, and are seen in patients with thymomas [231,239,315,316]. Antibodies directed toward leucine-rich glioma inactivated 1 are associated with epilepsy and limbic encephalitis, and are seen in patients without tumors [239,315].…”