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Abstract
Objective: To assess the clinical and immunologic findings in children with voltage-gated potassium channel (VGKC)-complex antibodies (Abs).
Methods: Thirty-nine of 363 sera, referred from 2 pediatric centers from 2007 to 2013, had been reported positive (>100 pM) for VGKC-complex Abs. Medical records were reviewed retrospectively and the patients' condition was independently classified as inflammatory (n = 159) or noninflammatory (n = 204). Positive sera (>100 pM) were tested/retested for the VGKC-complex Ab–positive complex proteins LGI1 and CASPR2, screened for binding to live hippocampal neurons, and 12 high-titer sera (>400 pM) tested by radioimmunoassay for binding to VGKC Kv1 subunits with or without intracellular postsynaptic density proteins.
Results: VGKC-complex Abs were found in 39 children, including 20% of encephalopathies and 7.6% of other conditions (p = 0.001). Thirty children had inflammatory conditions and 9 had noninflammatory etiologies but titers >400 pM (n = 12) were found only in inflammatory diseases (p < 0.0001). Four sera, including from 2 children with coexisting NMDA receptor Abs and one with Guillain-Barré syndrome and Abs to both LGI1 and CASPR2, bound to hippocampal neurons. None of the sera bound detectably to VGKC Kv1 subunits on live HEK cells, but 4 of 12 >400 pM sera immunoprecipitated VGKC Kv1 subunits, with or without postsynaptic densities, extracted from transfected cells.
Conclusion: Positive VGKC-complex Abs cannot be taken to indicate a specific clinical syndrome in children, but appear to be a nonspecific biomarker of inflammatory neurologic diseases, particularly of encephalopathy. Some of the Abs may bind to intracellular epitopes on the VGKC subunits, or to the intracellular interacting proteins, but in many the targets remain undefined.
GLOSSARY
- Ab=
- antibody;
- ADAM22 and 23=
- cytoskeletal scaffold, disintegrin, and metalloproteinase 22 and 23;
- ADS=
- acquired demyelinating syndromes;
- CASPR2=
- contactin-associated protein 2;
- CBA=
- cell-based assay;
- GAD=
- glutamic acid decarboxylase;
- GBS=
- Guillain-Barré syndrome;
- HEK=
- human embryonic kidney;
- 125I-DTX=
- 125I-dendrotoxin;
- ICD-10=
- International Classification of Diseases, Tenth Revision;
- IgG=
- immunoglobulin G;
- LGI1=
- leucine-rich, glioma inactivated;
- MAGUK=
- membrane-associated guanylate kinases;
- NMDAR=
- NMDA receptor;
- OMS=
- opsoclonus myoclonus syndrome;
- PSD93 and 95=
- postsynaptic density proteins 93 and 95;
- VGKC=
- voltage-gated potassium channel
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at Neurology.org
- Received January 5, 2015.
- Accepted in final form May 7, 2015.
- © 2015 American Academy of Neurology
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