title: Bone marrow clonogenic capability, cytokine production, and thymic output in patients with common variable immunodeficiency.
abstract: In patients with primary Ab deficiencies, hematological and immunological abnormalities are frequently observed. A regenerative failure of hemopoietic stem/progenitor cells has been hypothesized. We evaluated in the bone marrow (BM) of 11 patients with common variable immunodeficiency, the phenotype of BM progenitors and their in vitro growth by colony-forming cell (CFC) and long-term culture (LTC) assays. A significant decrease in erythroid and mixed CFC and, to a greater extent, in primitive LTC-CFC progenitors was observed in patients compared with healthy controls. The frequency of BM pre-B and pro-B cells correlated directly with the absolute number of CD19+ lymphocytes. BM cells cultured in vitro produced spontaneously lower amounts of IL-2 and elevated levels of TNF-alpha compared with controls, indicating a skewing toward a proapoptotic cytokine pattern. In addition, stromal cells generated after BM LTC secreted less IL-7 and displayed by immunohistochemistry an altered phenotype. These findings were associated with a significant decrease in naive Th cells coexpressing CD31 in the peripheral blood. These results indicate an impaired growth and differentiation capacity of progenitor cells in patients with common variable immunodeficiency.
authors.affiliation: Interregional Center for Primary Immunodeficiencies, Department of Clinical Medicine, University of Rome La Sapienza, and Azienda Policlinico Umberto I, Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Isgrò
authors.forename: Marco
authors.initials: M
authors.lastname: Marziali
authors.forename: Ivano
authors.initials: I
authors.lastname: Mezzaroma
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Luzi
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Mazzone
authors.forename: Vanessa
authors.initials: V
authors.lastname: Guazzi
authors.forename: Grazia
authors.initials: G
authors.lastname: Andolfi
authors.forename: Barbara
authors.initials: B
authors.lastname: Cassani
authors.forename: Alessandro
authors.initials: A
authors.lastname: Aiuti
authors.forename: Fernando
authors.initials: F
authors.lastname: Aiuti
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D001854:Bone Marrow Cells / Q000276:immunology* / Q000473:pathology*; D016022:Case-Control Studies; D003114:Colony-Forming Units Assay; D017074:Common Variable Immunodeficiency / Q000097:blood / Q000276:immunology* / Q000473:pathology*; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis; D015851:Interleukin-7 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D013950:Thymus Gland / Q000276:immunology* / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D007376:Interleukin-2; D015851:Interleukin-7; D014409:Tumor Necrosis Factor-alpha