Manuela Baronio1, Francesco Saettini2, Luisa Gazzurelli1, Daniele Moratto3, Vassilios Lougaris4, Stefano Rossi1, Antonio Marzollo5,6, Silvia Ricci7, Daniele Zama8, Boaz Palterer9, Canessa Clementina7, Lodi Lorenzo7, Marco Chiarini3, Alessandra Sottini10, Luisa Imberti10, Chiara Gorio11, Linda Rossini5, Raffaele Badolato1, Alessandro Plebani1. 1. Pediatrics Clinic and "A. Nocivelli" Institute for Molecular Medicine, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili of Brescia, Brescia, Italy. 2. Pediatric Hematology Oncology Unit, Department of Pediatrics, University of Milano Bicocca, MBBM Foundation, Monza, Italy. 3. Flow Cytometry Unit, Clinical Chemistry Laboratory, ASST Spedali Civili, Brescia, Italy. 4. Pediatrics Clinic and "A. Nocivelli" Institute for Molecular Medicine, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili of Brescia, Brescia, Italy. vlougarisbs@yahoo.com. 5. Pediatric Hematology, Oncology and Stem Cell Transplant Division, Padua University Hospital, Padua, Italy. 6. "Fondazione Città della Speranza", Institute of Pediatric Research, Padua, Italy. 7. Department of Health Sciences, Pediatric Immunology Unit, Meyer Children's University Hospital, University of Florence, Florence, Italy. 8. Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria of Bologna, Bologna, Italy. 9. Department of Clinical and Experimental Medicine, Unit of Allergology and Clinical Immunology, University of Florence, Florence, Italy. 10. CREA (AIL Center for Hemato-Oncologic Research), Diagnostic Department, ASST Spedali Civili of Brescia, Brescia, Italy. 11. Pediatric Oncohematology Unit, ASST Spedali Civili of Brescia, Brescia, Italy.
Abstract
PURPOSE: Jacobsen syndrome (JS) is a rare form of genetic disorder that was recently classified as a syndromic immunodeficiency. Available detailed immunological data from JS patients are limited. METHODS: Clinical and immunological presentation of twelve pediatric patients with JS by means of revision of clinical records, flow cytometry, real-time PCR, and lymphocyte functional testing were collected. RESULTS: Recurrent infections were registered in 6/12 patients (50%), while bleeding episodes in 2/12 (16.7%). White blood cell and absolute lymphocyte counts were reduced in 8/12 (66.7%) and 7/12 (58.3%) patients, respectively. Absolute numbers of CD3+ and CD4+ T cells were reduced in 8/12 (66.7%) and 7/12 (58.3%), respectively. Of note, recent thymic emigrants (RTE) were reduced in all tested patients (9/9), with T-cell receptor excision circle analysis (TRECs) showing a similar trend in 8/9 patients; naïve CD4+ T cells were low only in 5/11 patients (45.4%). Interestingly, B-cell counts, IgM memory B cells, and IgM serum levels were reduced in 10/12 (83.3%) patients. Natural killer (NK) cell counts were mostly normal but the percentages of CD16+CD56low/- cells were expanded in 7/7 patients tested. The observed immunological alterations did not correlate with patients' age. Finally, responses to proliferative stimuli were normal at presentation for all patients, although they may deteriorate over time. CONCLUSIONS: Our data suggest that patients affected with JS may display important numeric and maturational alterations in the T-, B-, and NK-cell compartments. These findings suggest that JS patients should be regularly monitored from an immunological point of view.
PURPOSE: Jacobsen syndrome (JS) is a rare form of genetic disorder that was recently classified as a syndromic immunodeficiency. Available detailed immunological data from JS patients are limited. METHODS: Clinical and immunological presentation of twelve pediatric patients with JS by means of revision of clinical records, flow cytometry, real-time PCR, and lymphocyte functional testing were collected. RESULTS: Recurrent infections were registered in 6/12 patients (50%), while bleeding episodes in 2/12 (16.7%). White blood cell and absolute lymphocyte counts were reduced in 8/12 (66.7%) and 7/12 (58.3%) patients, respectively. Absolute numbers of CD3+ and CD4+ T cells were reduced in 8/12 (66.7%) and 7/12 (58.3%), respectively. Of note, recent thymic emigrants (RTE) were reduced in all tested patients (9/9), with T-cell receptor excision circle analysis (TRECs) showing a similar trend in 8/9 patients; naïve CD4+ T cells were low only in 5/11 patients (45.4%). Interestingly, B-cell counts, IgM memory B cells, and IgM serum levels were reduced in 10/12 (83.3%) patients. Natural killer (NK) cell counts were mostly normal but the percentages of CD16+CD56low/- cells were expanded in 7/7 patients tested. The observed immunological alterations did not correlate with patients' age. Finally, responses to proliferative stimuli were normal at presentation for all patients, although they may deteriorate over time. CONCLUSIONS: Our data suggest that patients affected with JS may display important numeric and maturational alterations in the T-, B-, and NK-cell compartments. These findings suggest that JS patients should be regularly monitored from an immunological point of view.
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