title: Effect of chemotherapy and stem cell transplantation on T lymphocyte clones in familial haemophagocytic lymphohistiocytosis.
abstract: Familial haemophagocytic lymphohistiocytosis (FHL) is a rare disorder in infancy, curative only by an allogeneic stem cell transplantation (SCT). We recently confirmed the clonal evidence of T cells in FHL. To confirm the effect of chemotherapy and SCT in FHL, the change of T-cell clones was analysed in two patients using inverse reverse transcription-polymerase chain reaction (RT-PCR) of the T-cell receptor variable region (TCR V) gene, followed by PCR for the junctional region (Jbeta-PCR), a single-strand conformation polymorphism (SSCP) and sequencing analysis at diagnosis, after chemotherapy and after SCT. A high frequency (> 15%) of alphabeta T-cell clones and a predominant bias (Jbeta1:Jbeta2, 85:15) for the Jbeta1 subgroup were observed in the two patients at diagnosis. In one patient, however, an inverted predominant bias (Jbeta1:Jbeta2, 9:91) for the Jbeta2 subgroup and oligoclonal expansion were observed at relapse after chemotherapy. In the other patient, correction of both restricted Jbeta cluster usage and variation of TCR were observed after chemotherapy and SCT. Using sequence analysis, the clonal T cells detected at diagnosis were found to be substituted at low frequency (< 0.75%) by several new clones after chemotherapy and SCT. These results indicate that any genetic defect could influence the regulation of the T-cell network, and normalization of both the variation in each Vbeta repertoire and the Jbeta1/Jbeta2 ratio is needed to achieve remission, and might support the rationale that the only acceptable curative therapy of FHL is allogeneic SCT.
authors.affiliation: Department of First Internal Medicine, Fukuoka University, Japan. nkimura@fukuoka-u.ac.jp
authors.forename: N
authors.initials: N
authors.lastname: Kimura
authors.forename: E
authors.initials: E
authors.lastname: Ishii
authors.forename: M
authors.initials: M
authors.lastname: Sako
authors.forename: T
authors.initials: T
authors.lastname: Yoshida
authors.forename: M
authors.initials: M
authors.lastname: Nagano
authors.forename: H
authors.initials: H
authors.lastname: Takada
authors.forename: S
authors.initials: S
authors.lastname: Imashuku
authors.forename: K
authors.initials: K
authors.lastname: Tamura
mesh_terms: D002999:Clone Cells; D005260:Female; D005787:Gene Frequency; D019672:Genes, T-Cell Receptor; D018380:Hematopoietic Stem Cell Transplantation; D015616:Histiocytosis, Non-Langerhans-Cell / Q000235:genetics* / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007133:Immunoglobulin Joining Region / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007223:Infant; D008297:Male; D018807:Polymorphism, Single-Stranded Conformational; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region