Immunophenotypic analysis of the TCR-V beta repertoire in 98 persistent expansions of CD3(+)/TCR-alpha beta(+) large granular lymphocytes - Utility in assessing clonality and insights into the pathogenesis of the disease

• Type: Article in International Scientific Journal
• Date: 2001

Authors

Lima, M (Author) Other; Almeida, J (Author) Other; Santos, AH (Author) Other; Teixeira, MDA (Author) Other; Alguero, MDC (Author) Other; Queiros, ML (Author) Other; Balanzategui, A (Author) Other; Justica, B (Author) Other; Gonzalez, M (Author) Other; Miguel, JFS (Author) Other; Orfao, A (Author) Other

Journal

Title: American Journal of Pathology

Vol. 159

Pages: 1861-1868

ISSN: 0002-9440

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 75 Citations

Scopus - 76 Citations

Other information

Authenticus ID: P-000-SSN

DOI: 10.1016/s0002-9440(10)63032-5

Abstract (EN): At present, a major challenge in the initial diagnosis of leukemia of large granular lymphocytes (LGLs) is to establish the clonal nature of the expanded population. in the present study we have analyzed by flow cytometry immunophenotyping the TCR-V beta repertoire of 98 consecutive cases of persistent expansions of CD4(+) or CD8(+bright)CD3(+)/TCR-alpha beta (+) LGLs and compared the results with those obtained in molecular studies of TCR-beta gene rearrangements. Fifty-eight cases were considered to be monoclonal in molecular studies whereas in the remaining 40 cases there was no evidence for monoclonality (11 cases were considered oligoclonal and 29 polyclonal). The TCR-V beta repertoire was biased to the preferential use of one or more TCR-V beta families in 96% of cases, a total of 124 TCR-V beta expansions being diagnosed: one TCR-V beta expansion in 71 cases and two or more TCR-V beta expansions in 23 cases. The highest TCR-V beta expansion observed in each case was higher among monoclonal (74 +/- 19%) as compared to nonmonoclonal cases (24 +/- 14%) (P = 0.001), as did the fraction of LGLs that exhibited a TCR-V beta -restricted pattern (86 +/- 16% and 42 +/- 23%, respectively; P = 0.0001); by contrast, the proportion of cases displaying more than one TCR-V beta expansion was higher in the latter group: 7% versus 48%, respectively (P = 0.001). Results obtained in oligoclonal cases were intermediate between those obtained in polyclonal and monoclonal cases and similar results were observed for CD4(+) as for CD8(+bright) T-cell expansions. TCR-V beta families expressed in CD8(+bright) T-cell-LGL proliferations showed a pattern of distribution that mimics the frequency at which the individual TCR-V beta families are represented in normal peripheral blood T cells. Assuming that a given proliferation of LGLs is monoclonal whenever there is an expansion of a given TCR-V beta family of at least 40% of the total CD4(+) or CD8(+bright) T-cell. compartment, we were able to predict clonality with a sensitivity of 93% and a specificity of 80%. By increasing the cut-off value to 60%, sensitivity and specificity were of 81% and 100%. In summary, our results suggest that flow cytometry immunophenotypic analysis of the TCR-V beta repertoire is a powerful screening toot for the assessment of T-cell clonality in persistent expansions of TCR-alpha beta (+) LGLs.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8