The kinetics of early T and B cell immune recovery after bone marrow transplantation in RAG-2-deficient SCID patients

Atar Lev, Amos J. Simon, Mor Bareket, Bella Bielorai, Daphna Hutt, Ninette Amariglio, Gideon Rechavi, Raz Somech

    Research output: Contribution to journalArticle

    36 Scopus citations

    Abstract

    The kinetics of T and B cell immune recovery after bone marrow transplantation (BMT) is affected by many pre- and post-transplant factors. Because of the profoundly depleted baseline T and B cell immunity in recombination activating gene 2 (RAG-2)-deficient severe combined immunodeficiency (SCID) patients, some of these factors are eliminated, and the immune recovery after BMT can then be clearly assessed. This process was followed in ten SCID patients in parallel to their associated transplant-related complications. Early peripheral presence of T and B cells was observed in 8 and 4 patients, respectively. The latter correlated with pre-transplant conditioning therapy. Cells from these patients carried mainly signal joint DNA episomes, indicative of newly derived B and T cells. They were present before the normalization of the T cell receptor (TCR) and the B cell receptor (BCR) repertoire. Early presentation of the ordered TCR gene rearrangements after BMT occurred simultaneously, but this pattern was heterogeneous over time, suggesting different and individual thymic recovery processes. Our findings early after transplant could suggest the long-term patients' clinical outcome. Early peripheral presence of newly produced B and T lymphocytes from their production and maturation sites after BMT suggests donor stem cell origin rather than peripheral expansion, and is indicative of successful outcome. Peripheral detection of TCR excision circles and kappa-deleting recombination excision circles in RAG-2-deficient SCID post-BMT are early markers of T and B cell reconstitution, and can be used to monitor outcome and tailor specific therapy for patients undergoing BMT.

    Original languageEnglish (US)
    Article numbere30494
    JournalPloS one
    Volume7
    Issue number1
    DOIs
    StatePublished - Jan 25 2012

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)
    • Agricultural and Biological Sciences(all)
    • General

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    Lev, A., Simon, A. J., Bareket, M., Bielorai, B., Hutt, D., Amariglio, N., Rechavi, G., & Somech, R. (2012). The kinetics of early T and B cell immune recovery after bone marrow transplantation in RAG-2-deficient SCID patients. PloS one, 7(1), [e30494]. https://doi.org/10.1371/journal.pone.0030494