Molecular analysis of the CDR3 encoding region of the immunoglobulin heavy chain locus in cerebrospinal fluid cells as a diagnostic tool in lymphomatous meningitis.

Abstract

The diagnosis of leptomeningeal B-cell lymphoma is based on the identification of malignant B cells in the cerebrospinal fluid (CSF). Frequently, cytology does not allow clear distinction between neoplastic lymphoid cells and reactively transformed mononuclear cells. Individual B-cell clones can be identified on the basis of DNA sequences that encode the highly diverse complementarity-determining region (CDR3) of the immunoglobulin heavy chain locus (IgH). We studied CSF samples from 5 patients with B-cell malignancies and cytological evidence of leptomeningeal involvement, using polymerase chain reaction (PCR)-based high-resolution capillary electrophoresis and automated fluorescence analysis to detect PCR fragments. As controls, we assessed CSF specimens from 7 patients with inflammatory neurological diseases and three samples without pathological findings. In all patients with B-cell malignancies, a single PCR product was generated, indicating that CDR3-specific fragments were derived from monoclonal cell populations. CSF samples from patients with inflammatory diseases yielded multiple CDR3 amplicons, suggesting the presence of a polyclonal B-cell activation. No PCR product could be amplified in normal CSF samples. Automated fluorescence detection of CDR3 fragments is a highly sensitive and rapid method to distinguish neoplastic monoclonal and reactive polyclonal B-cell populations in the CSF.

• Authors: B Storch-Hagenlocher, J Haas, M E Vogt-Schaden, M Bentz, L A Hoffmann, A Biessmann, B Wildemann
• Journal: Annals of neurology (Ann Neurol) Vol. 47 Issue 2 Pg. 211-7 (Feb 2000) ISSN: 0364-5134 [Print] United States
• PMID: 10665492 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Complementarity Determining Regions
• Immunoglobulin Heavy Chains
• Immunoglobulin Variable Region

Topics

• Base Sequence (genetics)
• Cerebrospinal Fluid (cytology, physiology)
• Chromosome Mapping
• Complementarity Determining Regions
• Electrophoresis, Capillary
• Fluorescence
• Humans
• Immunoglobulin Heavy Chains (genetics)
• Immunoglobulin Variable Region (genetics)
• Lymphoma, B-Cell (complications)
• Meningitis, Aseptic (cerebrospinal fluid, diagnosis, etiology)
• Polymerase Chain Reaction