Investigations of Caspr2, an Autoantigen of Encephalitis and Neuromyotonia
Por:
Lancaster, E, Huijbers, MGM, Bar, V, Boronat, A, Wong, A, Martinez-Hernandez, E, Wilson, C, Jacobs, D, Lai, M, Walker, RW, Graus, F, Bataller, L, Illa, I, Markx, S, Strauss, KA, Peles, E, Scherer, SS, Dalmau, J
Publicada:
1 feb 2011
Resumen:
Objective: To report clinical and immunological investigations of contactin-associated protein-like 2 (Caspr2), an autoantigen of encephalitis and peripheral nerve hyperexcitability (PNH) previously attributed to voltage-gated potassium channels (VGKC).
Methods: Clinical analysis was performed on 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.
Results: Using Caspr2-expressing cells, antibodies were identified in 8 patients but not in 140 patients with several types of autoimmune or viral encephalitis, PNH, or mutations of the Caspr2-encoding gene. Patients' antibodies reacted with brain and peripheral nerve in a pattern that colocalized with Caspr2. This reactivity was abrogated after immunoabsorption with Caspr2 and was absent in tissues from Caspr2-null mice. Of the 8 patients with Caspr2 antibodies, 7 had encephalopathy or seizures, 5 neuropathy or PNH, and 1 isolated PNH. Three patients also had myasthenia gravis, bulbar weakness, or symptoms that initially suggested motor neuron disease. None of the patients had active cancer; 7 responded to immunotherapy and were healthy or only mildly disabled at last follow-up (median, 8 months; range, 6-84 months).
Interpretation: Caspr2 is an autoantigen of encephalitis and PNH previously attributed to VGKC antibodies. The occurrence of other autoantibodies may result in a complex syndrome that at presentation could be mistaken for a motor neuron disorder. Recognition of this disorder is important, because it responds to immunotherapy. ANN NEUROL 2011;69:303-311
Filiaciones:
Bar, V:
Weizmann Inst Sci, Dept Mol Cellular Biol, IL-76100 Rehovot, Israel
Walker, RW:
St Josephs Hosp, Barrow Neurol Inst, Phoenix, AZ USA
Graus, F:
Univ Barcelona, Hosp Clin, Serv Neurol, Barcelona, Spain
IDIBAPS, Barcelona, Spain
Bataller, L:
Univ Hosp La Fe, Dept Neurol, Valencia, Spain
Illa, I:
Univ Autonoma Barcelona, Hosp St Pau, Dept Neurol, E-08193 Barcelona, Spain
Markx, S:
Columbia Univ, Dept Psychiat, Coll Phys & Surg, New York, NY USA
Strauss, KA:
Clin Special Children, Strasburg, PA USA
Franklin & Marshall Coll, Dept Biol, Lancaster, PA 17604 USA
Lancaster Gen Hosp, Lancaster, PA USA
Peles, E:
Weizmann Inst Sci, Dept Mol Cellular Biol, IL-76100 Rehovot, Israel
Dalmau, J:
Univ Penn, Div Neurooncol, Dept Neurol, Sch Med, Philadelphia, PA 19104 USA
Green Accepted
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