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Browsing by Author "SAN MIGUEL, J.F."

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  • Immunophenotypic analysis of the TCR‐Vbeta repertoire in 98 persistent expansions of CD3(+)/TCR‐alphabeta(+) large granular lymphocytes: utility in assessing clonality and insights into the pathogenesis of the disease
    Publication . LIMA, M.; ALMEIDA, J.; SANTOS, A.H.; DOS ANJOS TEIXEIRA, M.; ALGUERO, M.C.; QUEIROS, M.L.; BALANZATEGUI, A.; JUSTICA, B.; GONZALEZ, M.; SAN MIGUEL, J.F.; ORFAO, A.
    Am J Pathol. 2001 Nov;159(5):1861-8. Immunophenotypic analysis of the TCR-Vbeta repertoire in 98 persistent expansions of CD3(+)/TCR-alphabeta(+) large granular lymphocytes: utility in assessing clonality and insights into the pathogenesis of the disease. Lima M, Almeida J, Santos AH, dos Anjos Teixeira M, Alguero MC, Queirós ML, Balanzategui A, Justiça B, Gonzalez M, San Miguel JF, Orfão A. Serviço de Hematologia Clínica, Unidade de Citometria, Hospital Geral de Santo António, Porto, Portugal. mmc.lima@clix.pt Abstract 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-Vbeta repertoire of 98 consecutive cases of persistent expansions of CD4(+) or CD8(+bright) CD3(+)/TCR-alphabeta(+) 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-Vbeta repertoire was biased to the preferential use of one or more TCR-Vbeta families in 96% of cases, a total of 124 TCR-Vbeta expansions being diagnosed: one TCR-Vbeta expansion in 71 cases and two or more TCR-Vbeta expansions in 23 cases. The highest TCR-Vbeta 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-Vbeta-restricted pattern (86 +/- 16% and 42 +/- 23%, respectively; P = 0.0001); by contrast, the proportion of cases displaying more than one TCR-Vbeta 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-Vbeta families expressed in CD8(+bright) T-cell-LGL proliferations showed a pattern of distribution that mimics the frequency at which the individual TCR-Vbeta 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-Vbeta 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-Vbeta repertoire is a powerful screening tool for the assessment of T-cell clonality in persistent expansions of TCR-alphabeta(+) LGLs. PMID: 11696446 [PubMed - indexed for MEDLINE]PMCID: PMC1867049
    2001-11Journal article Open access Show more
  • Immunophenotypic approach to the identification and
    Publication . PEREZ‐ANDRES, M.; SANTIAGO, M.; ALMEIDA, J.; MATEO, G.; PORWIT‐MACDONALD, A.; BJORKLUND, E.; VALET, G.; KRAAN, J.; GRATAMA, J.W.; D'HAUTCOURT, J.L.; MERLE‐BERAL, H.; LIMA, M.; MONTALBAN, M.A.; SAN MIGUEL, J.F.; ORFAO, I.; EUROPEAN WORKING GROUP ON CLINICAL CELL ANALYSIS, SPANISH NETWORK ON
    Biol Regul Homeost Agents. 2004 Jul-Dec;18(3-4):392-8. Immunophenotypic approach to the identification and characterization of clonal plasma cells from patients with monoclonal gammopathies. Pérez-Andrés M, Santiago M, Almeida J, Mateo G, Porwit-MacDonald A, Bjorklund E, Valet G, Kraan J, Gratama JW, D'Hautcourt JL, Merle-Beral H, Lima M, Montalban MA, San Miguel JF, Orfao I; European Working Group on Clinical Cell Analysis; Spanish Network on Multiple Myeloma. Service of Cytometry, Centro de Investigación del Cáncer, Salamanca, Spain. PMID: 15786710 [PubMed - indexed for MEDLINE]
    2004-07Journal article Open access Show more
  • TCRalphabeta+/CD4+ large granular lymphocytosis: a new clonal T‐cell lymphoproliferative disorder.
    Publication . LIMA, M.; ALMEIDA, J.; DOS ANJOS TEIXEIRA, M.; ALGUERO, M.D.; MDEL, C.; SANTOS, A.H.; BALANZATEGUI, A.; QUEIROS, M.L.; BARCENA, P.; IZARRA, A.; FONSECA, S.; BUENO, C.; JUSTICA, B.; GONZALEZ, M.; SAN MIGUEL, J.F.; ORFAO, A.
    Am J Pathol. 2003 Aug;163(2):763-71. TCRalphabeta+/CD4+ large granular lymphocytosis: a new clonal T-cell lymphoproliferative disorder. Lima M, Almeida J, Dos Anjos Teixeira M, Alguero Md Mdel C, Santos AH, Balanzategui A, Queirós ML, Bárcena P, Izarra A, Fonseca S, Bueno C, Justiça B, Gonzalez M, San Miguel JF, Orfao A. Serviço de Hematologia Clinica, Unidade de Citometria, Hospital Geral de Santo Antonio, Porto, Portugal. Abstract Large granular lymphocyte (LGL) leukemia is a well-recognized disease of mature T-CD8(+) or less frequently natural killer cells; in contrast, monoclonal expansions of CD4(+) T-LGL have only been sporadically reported in the literature. In the present article we have explored throughout a period of 56 months the incidence of monoclonal expansions of CD4(+) T-LGL in a population of 2.2 million inhabitants and analyzed the immunophenotype and the pattern of cytokine production of clonal CD4(+) T cells of a series of 34 consecutive cases. Like CD8(+) T-LGL leukemias, CD4(+) T-LGL leukemia patients have an indolent disease; however, in contrast to CD8(+) T-LGL leukemias, they do not show cytopenias and autoimmune phenomena and they frequently have associated neoplasias, which is usually determining the clinical course of the disease. Monoclonal CD4(+) T-LGLshowed expression of TCRalphabeta, variable levels of CD8 (CD8(-/+dim)) and a homogeneous typical cytotoxic (granzyme B(+), CD56(+), CD57(+), CD11b(+/-)) and activated/memory T cell (CD2(+bright), CD7(-/+dim), CD11a(+bright), CD28(-), CD62L(-) HLA-DR(+)) immunophenotype. In addition, they exhibited a Th1 pattern of cytokine production [interferon-gamma(++), tumor necrosis factor-alpha(++), interleukin (IL-2)(-/+), IL-4(-), IL-10(-), IL-13(-)]. Phenotypic analysis of the TCR-Vbeta repertoire revealed large monoclonal TCR-Vbeta expansions; only a restricted number of TCR-Vbeta families were represented in the 34 cases analyzed. These findings suggest that monoclonal TCRalphabeta(+)/CD4(+)/NKa(+)/CD8(-/+dim) T-LGL represent a subgroup of monoclonal LGL lymphoproliferative disorders different from both CD8(+) T-LGL and natural killer cell-type LGL leukemias. Longer follow-up periods are necessary to determine the exact significance of this clonal disorder.
    2003-08Journal article Open access Show more