Analysis of antibody gene rearrangement, usage, and specificity in chronic focal encephalitis

S. E. Baranzini, K. Laxer, R. Saketkhoo, M. K. Elkins, J. M. Parent, R. Mantegazza, J. R. Oksenberg

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Background: Autoantibodies have been implicated in the development of chronic focal encephalitis (CFE) or Rasmussen's disease, a progressive and intractable form of epilepsy characterized by uncontrollable unilateral focal seizures, brain atrophy, and inflammation. Objective: To investigate the origin and characteristics of the B cell population that trigger or sustain brain inflammation in patients with CFE. Methods: The authors used immunoglobulin (Ig) complementary determining region 3 (CDR3)-size spectratyping and DNA sequencing to examine the rearranged IgG heavy chain (IgGH) transcript repertoire in resected brain samples from four patients with CFE. They also performed Western blotting on human and rat brain homogenates and immunostaining on a human neuronal cell line to test the reactivity of sera from patients with CFE. Results: The authors observed substantial perturbations from the normal, unstimulated repertoire of immunoglobulin genes. Sequencing of randomly selected clones confirmed the restricted profile and provided evidence for somatic mutation patterns characteristic of antigen-specific stimulation. They also observed IgGVH-CDR3 sequence diversity among patients. When sera were assayed from patients with CFE for specificity against rat and human brain homogenates, heterogeneous reactivity patterns were detected among patients. Immunostaining of postmitotic human neuronal cells demonstrated reactivity of some patients' sera against neural antigens. Conclusions: These findings support an important role for clonally expanded B lymphocytes in some forms of epilepsy, but also indicate a wide spectrum of reactivity characteristic of antigenic heterogeneity.

Original languageEnglish
Pages (from-to)709-716
Number of pages8
JournalNeurology
Volume58
Issue number5
Publication statusPublished - Mar 12 2002

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Gene Rearrangement
Encephalitis
Antibodies
Brain
B-Lymphocytes
Serum
Antigens
Immunoglobulin Genes
DNA Sequence Analysis
Autoantibodies
Atrophy
Immunoglobulins
Epilepsy
Seizures
Clone Cells
Immunoglobulin G
Western Blotting
Cell Line
Mutation
Population

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Baranzini, S. E., Laxer, K., Saketkhoo, R., Elkins, M. K., Parent, J. M., Mantegazza, R., & Oksenberg, J. R. (2002). Analysis of antibody gene rearrangement, usage, and specificity in chronic focal encephalitis. Neurology, 58(5), 709-716.

Analysis of antibody gene rearrangement, usage, and specificity in chronic focal encephalitis. / Baranzini, S. E.; Laxer, K.; Saketkhoo, R.; Elkins, M. K.; Parent, J. M.; Mantegazza, R.; Oksenberg, J. R.

In: Neurology, Vol. 58, No. 5, 12.03.2002, p. 709-716.

Research output: Contribution to journalArticle

Baranzini, SE, Laxer, K, Saketkhoo, R, Elkins, MK, Parent, JM, Mantegazza, R & Oksenberg, JR 2002, 'Analysis of antibody gene rearrangement, usage, and specificity in chronic focal encephalitis', Neurology, vol. 58, no. 5, pp. 709-716.
Baranzini SE, Laxer K, Saketkhoo R, Elkins MK, Parent JM, Mantegazza R et al. Analysis of antibody gene rearrangement, usage, and specificity in chronic focal encephalitis. Neurology. 2002 Mar 12;58(5):709-716.
Baranzini, S. E. ; Laxer, K. ; Saketkhoo, R. ; Elkins, M. K. ; Parent, J. M. ; Mantegazza, R. ; Oksenberg, J. R. / Analysis of antibody gene rearrangement, usage, and specificity in chronic focal encephalitis. In: Neurology. 2002 ; Vol. 58, No. 5. pp. 709-716.
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