Bone marrow clonogenic capability, cytokine production, and thymic output in patients with common variable immunodeficiency.
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.
Isgrò
Antonella
A
Interregional Center for Primary Immunodeficiencies, Department of Clinical Medicine, University of Rome La Sapienza, and Azienda Policlinico Umberto I, Rome, Italy.
Marziali
Marco
M
Mezzaroma
Ivano
I
Luzi
Giuseppe
G
Mazzone
Anna Maria
AM
Guazzi
Vanessa
V
Andolfi
Grazia
G
Cassani
Barbara
B
Aiuti
Alessandro
A
Aiuti
Fernando
F
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
D016207:Cytokines; D007376:Interleukin-2; D015851:Interleukin-7; D014409:Tumor Necrosis Factor-alpha