Analysis of antibody gene rearrangement, usage, and specificity in chronic focal encephalitis.
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.
Baranzini
S E
SE
Department of Neurology, University of California at San Francisco, 94143, USA.
Laxer
K
K
Saketkhoo
R
R
Elkins
M K
MK
Parent
J M
JM
Mantegazza
R
R
Oksenberg
J R
JR
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000502:physiology; D001921:Brain / Q000276:immunology* / Q000473:pathology; D022801:Complementarity Determining Regions / Q000235:genetics* / Q000378:metabolism; D004660:Encephalitis / Q000276:immunology* / Q000503:physiopathology; D005260:Female; D015322:Gene Rearrangement, B-Lymphocyte; D005803:Genes, Immunoglobulin; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics* / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D008297:Male; D008875:Middle Aged; D051381:Rats; D017207:Rats, Sprague-Dawley
D022801:Complementarity Determining Regions; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains