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Molecular analysis of the CDR3 encoding region of the immunoglobulin heavy chain locus in cerebrospinal fluid cells as a diagnostic tool in lymphomatous meningitis
Author(s) -
StorchHagenlocher Brigitte,
Haas Jürgen,
VogtSchaden Maria Elisabeth,
Bentz Martin,
Hoffmann Lisa Ann,
Biessmann Annette,
Wildemann Brigitte
Publication year - 2000
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/1531-8249(200002)47:2<211::aid-ana11>3.0.co;2-9
Subject(s) - cerebrospinal fluid , biology , polymerase chain reaction , polyclonal antibodies , microbiology and biotechnology , amplicon , antibody , monoclonal , b cell , pathology , immunoglobulin light chain , complementarity determining region , monoclonal antibody , immunology , medicine , gene , genetics
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. Ann Neurol 2000;47:211–217