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International Immunology Advance Access published online on November 22, 2005
International Immunology, doi:10.1093/intimm/dxh343
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© The Japanese Society for Immunology. 2005. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Received June 5, 2005
Accepted September 30, 2005

Article

Different B-cell populations are responsible for the peripheral and intrathecal antibody production in neuroborreliosis

András Lakos 1 *, Emoke Ferenczi 2, Sámuel Komoly 3, and Marta Granström 4

1 Center for Tick-borne Diseases, Visegrádi 14, H-1132 Budapest, Hungary
2 Department of Virology, Johan Béla National Center for Epidemiology, Gyáli u 2-6, H-1096 Budapest, Hungary
3 National Center for Neuroimmunology, Jahn Ferenc Teaching Hospital, Köves u. 2-4, H-1204 Budapest, Hungary; Department of Neurology, University of Pécs, Rét u. 2, 7623 Pécs, Hungary
4 Department of Clinical Microbiology, Microbiology and Tumorbiology Center (MTC), Karolinska Hospital, SE-171 76 Stockholm, Sweden

* To whom correspondence should be addressed.
András Lakos, E-mail: alakos{at}axelero.hu


  Abstract

The diagnosis of neuroborreliosis (NB)--a serious complication of Lyme disease--relies on demonstration of intrathecal borrelia antibody production. We hypothesized that if a qualitative difference between the cerebrospinal fluid and the serum immunoblot-banding patterns was observed, then the borrelia antibodies found in the CSF could not be the result of leakage of serum antibodies to the CSF due to blood-brain barrier damage, but rather had to be produced intrathecally. CSF/serum pairs from 69 NB patients and from 85 control patients with other neurological disorders were investigated. All samples were tested blindly by immunoblot and a commercial capture ELISA kit for NB. The concordance between the two methods was 85.7%. When using the other method as reference, the accuracy of the two assays in the two patient materials was similar: 80% for sensitivity and 95% for specificity. Four types of comparative immunoblot-banding patterns that reflected intrathecal borrelia antibody synthesis were distinguished. The study showed that a simple comparison between the immunoblot pattern of serum and CSF samples allows for a reliable diagnosis of NB by demonstration of intrathecal antibody production. This is the first study to show that a qualitative difference of the antibody response between the immune response of serum and CSF is a rule. The findings also imply that partly different B-cell populations are responsible for the antibody production in the blood and in the central nervous system. In addition, our observation provides possible implications for other infectious diseases with CNS involvement.

Keywords: Borrelia burgdorferi; comparative immunoblot assay; intrathecal antibody synthesis; Lyme disease; neuroborreliosis.
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