Quantification of newly produced B and T lymphocytes in untreated chronic lymphocytic leukemia patients
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RESEARCH
Open Access
Quantification of newly produced B and T lymphocytes in untreated chronic lymphocytic leukemia patients Marina Motta1, Marco Chiarini2, Claudia Ghidini2, Cinzia Zanotti2, Cinzia Lamorgese1, Luigi Caimi2, Giuseppe Rossi1, Luisa Imberti2*
Abstract Background: The immune defects occurring in chronic lymphocytic leukemia are responsible for the frequent occurrence of infections and autoimmune phenomena, and may be involved in the initiation and maintenance of the malignant clone. Here, we evaluated the quantitative defects of newly produced B and T lymphocytes. Methods: The output of B and T lymphocytes from the production and maturation sites was analyzed in chronic lymphocytic leukemia patients and healthy controls by quantifying kappa-deleting recombination excision circles (KRECs) and T-cell receptor excision circles (TRECs) by a Real-Time PCR assay that simultaneously detects both targets. T-lymphocyte subsets were analyzed by six-color flow cytometric analysis. Data comparison was performed by two-sided Mann-Whitney test. Results: KRECs level was reduced in untreated chronic lymphocytic leukemia patients studied at the very early stage of the disease, whereas the release of TRECs+ cells was preserved. Furthermore, the observed increase of CD4+ lymphocytes could be ascribed to the accumulation of CD4+ cells with effector memory phenotype. Conclusions: The decreased number of newly produced B lymphocytes in these patients is likely related to a homeostatic mechanism by which the immune system balances the abnormal B-cell expansion. This feature may precede the profound defect of humoral immunity characterizing the later stages of the disease.
Background Profound defects of both humoral and cell-mediated immunity have been described in patients with chronic lymphocytic leukemia (CLL), a disease characterized by the accumulation of mature, malignant, monoclonal B lymphocytes in blood, lymph nodes, spleen, liver, and bone marrow [1]. The disease is characterized by the presence of immune defects, responsible for the frequent occurrence of infections and autoimmune phenomena, that may be involved in the initiation and maintenance of the malignant clone. The immune abnormalities include reduced immunoglobulin (Ig) levels, as well as qualitative and quantitative defects of B, T, NK cells, neutrophils, and the monocyte/ * Correspondence: [email protected] 2 Laboratory of Biotechnology, Diagnostic Department, Spedali Civili, Piazzale Spedali Civili 1, 25123, Brescia, Italy Full list of author information is available at the end of the article
macrophage lineage [2,3]. All these immunological changes are linked to an increased frequency and severity of infections [3]. Since CLL represents a heterogeneous disease with a very variable outcome, a reliable prognosis at the time of initial diagnosis is difficult to predict; similarly, only few early markers anticipating the immune defects arising in the later stages of the disease have been up to now identified. In this context, a small size of the bloo
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