Immune deficiencies, infection, and systemic immune disordersDefect of regulatory T cells in patients with Omenn syndrome
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Patients
Eight patients with RAG1 defects and 1 patient with a RAG2 defect previously described (patient 512) were included in this study. The clinical, immunologic, and molecular features of the patients, consistent with OS, are outlined in Table I, Table II. Briefly, patient 1 was a boy who presented in the first days of life with erythrodermia, lymphadenopathy, spleen, and liver enlargement. Laboratory analysis showed leukocytosis (59 × 103 cells/μL) with marked eosinophilia (40 × 103 cells/μL) and
Phenotypic characterization of FOXP3+ cells in the peripheral blood of patients with OS
We analyzed CD4+ CD25+ FOXP3+ T cells from the peripheral blood of 4 patients with OS caused by mutations in the RAG1 gene (Table I). The percentage of FOXP3+ cells among the CD4+CD25+ cells were in the normal range for patients 1, 2, and 4, whereas in patient 3, this subset was markedly increased (Fig 1, A). Quantitative analysis of the absolute number of CD4+ FOXP3+ cells showed broad variability in these patients (Fig 1, B). Interestingly, the 2 patients (patients 1 and 2) displaying the
Discussion
In this article, we demonstrate that patients with OS have a variable number of circulating FOXP3+ T lymphocytes. However, at variance from what was observed in normal individuals, circulating FOXP3+ cells in patients with OS coexpress activation markers and fail to suppress proliferation of allogenic activated CD4+ T cells. OS is characterized by a profound impairment of T lymphocyte generation and abnormalities in the mechanisms that govern central tolerance. In this context, it is likely
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This work was supported by grants from the Italian Telethon Foundation to A.V., from Fondazione Cariplo (Nobel project to A.V., and L.D.N./R.B.), Fondazione Cariplo to A.V. and P.L.P., EU grant FP7 HLH-cure (project n. 201461), PRIN 2007 n. 2007ACZMMZ_005, Telethon GGP07241 to R.B., grant FIRB/MIUR (n. RBIN04CHXT) to P.V., Ministero della Salute RF2007 Giovani Ricercatori Grant to C.S., and the Manton Foundation to L.D.N.
Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.
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These authors share senior authorship of this work.