BACKGROUND. Although familial hemophagocytic lymphohistiocytosis (FHL) has been considered a T-cell disorder, to the authors' knowledge there are no previous reports on the clonal basis of FHL. In the current study the authors analyzed the clonality of T-cells in two FHL patients at the time of disease onset and at disease progression. METHODS. Patient 1 had FHL and died of recurrent disease 4 months after bone marrow transplantation (BMT). His liver and spleen showed massive infiltrations of CD3+, CD4-, and CD8+ T-cells. The Epstein-Barr virus (EBV) genome was detected by in situ hybridization. Patient 2 also had FHL and died of progressive disease 9 weeks after the onset of disease despite chemotherapy. A polymerase chain reaction (PCR) analysis showed positive EBV genome in the peripheral blood, liver, and spleen of Patient 2. In the two patients, T-cell receptor-β and α-chain variable region (TCR Vβ and Vα) repertoires in peripheral mononuclear cells were analyzed at the time of disease onset and at disease progression by the inverse PCR method. When a high usage (> 15%) of a specific Vβ family member was observed, a clonal analysis was performed by PCR using β-chain joining region (Jβ) primers. The clonality of specific Vβ-Jβ fragments was confirmed by a single strand confirmation polymorphism (SSCP) analysis. RESULTS. Although there was no preferential usage of Vβ in Patient 1, the exclusive expression of Jβ1.2 for Vβ13 was observed. A high frequency of Vβ13 also was observed at the time of disease progression, but the Jβ fragment for Vβ13 was polyclonal. In Patient 2, the restricted usage of Jβ1.6 for Vβ5a was observed at the time of disease onset, whereas Jβ1.1 and 1.2 for Vβ4 were observed exclusively at the time of disease progression. The clonality of Vβ13-Jβ1.2 in Patient 1 and Vβ5a-Jβ1.6 and Vβ4-Jβ1.1/Jβ1.2 in Patient 2 was confirmed by SSCP analysis. CONCLUSIONS. These findings suggest that the polyclonal T-cell lymphoproliferative disease associated with EBV was induced after BMT in Patient 1, and that the clonal change of expanded T-cells also was induced by EBV in Patient 2. The clonal analysis of T-cells is a useful tool to clarify the pathogenesis of FHL.
|Number of pages||8|
|Publication status||Published - Apr 1 1999|
All Science Journal Classification (ASJC) codes
- Cancer Research