Davide Montin1, Agostina Marolda2, Francesco Licciardi3, Francesca Robasto1, Silvia Di Cesare4, Emanuela Ricotti1, Francesca Ferro5, Giacomo Scaioli6, Carmela Giancotta7, Donato Amodio4, Francesca Conti7, Giuliana Giardino8, Lucia Leonardi9, Silvia Ricci10, Stefano Volpi11, Lucia Augusta Baselli12, Chiara Azzari10, Grazia Bossi13, Rita Consolini14, Rosa Maria Dellepiane12, Marzia Duse9, Marco Gattorno11, Baldassarre Martire15, Maria Caterina Putti16, Annarosa Soresina17, Alessandro Plebani17, Ugo Ramenghi1, Silvana Martino1, Claudio Pignata8, Caterina Cancrini4. 1. Division of Pediatric Immunology and Rheumatology, Department of Public Health and Pediatrics, "Regina Margherita" Children Hospital, University of Turin, Turin, Italy. 2. Division of Pediatric Immunology and Rheumatology, Department of Public Health and Pediatrics, "Regina Margherita" Children Hospital, University of Turin, Turin, Italy; Department of Health Sciences, A. Avogadro University of Eastern Piedmont, Novara, Italy. 3. Division of Pediatric Immunology and Rheumatology, Department of Public Health and Pediatrics, "Regina Margherita" Children Hospital, University of Turin, Turin, Italy. Electronic address: francesco.licciardi@gmail.com. 4. University Department of Pediatrics, Unit of Immune and Infectious Diseases, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy; Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy. 5. Division of Pediatric Immunology and Rheumatology, Department of Public Health and Pediatrics, "Regina Margherita" Children Hospital, University of Turin, Turin, Italy; Division of Microbiology and Virology, Maggiore della Carità Hospital, Novara, Italy. 6. Department of Public Health, University of Turin, Turin, Italy. 7. University Department of Pediatrics, Unit of Immune and Infectious Diseases, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy. 8. Department of Pediatrics, "Federico II" University of Naples, Naples, Italy. 9. Department of Pediatrics, La Sapienza University of Rome, Rome, Italy. 10. Division of Immunology, Section of Pediatrics, Department of Health Sciences, University of Florence and Anna Meyer Children's Hospital, Florence, Italy. 11. Pediatric and Rheumatology Clinic, Center for Autoinflammatory Diseases and Immunodeficiencies, Istituto Giannina Gaslini and University of Genoa, Genoa, Italy. 12. Department of Pediatrics, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy. 13. Department of Pediatrics, IRCCS San Matteo Hospital Foundation, Pavia, Italy. 14. Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. 15. Pediatric Hematology and Oncology Unit, "Policlinico-Giovanni XXIII" Hospital, University of Bari, Bari, Italy. 16. Pediatric Hematology-Oncology Unit, Department of Women's and Children's Health, Azienda Ospedaliera-University of Padova, Padua, Italy. 17. Pediatrics Clinic and Institute of Molecular Medicine "A. Nocivelli," University and Spedali Civili, Brescia, Italy.
Abstract
BACKGROUND: Patients with 22q11.2 deletion syndrome (22q11.2DS) may develop severe thrombocytopenic purpura and hemolytic anemia. There are no reliable predictors for the development of hematologic autoimmunity (HA) in these patients. OBJECTIVE: To describe the peculiar B and T subpopulation defects in patients with 22q11DS who have developed HA and test if these defects precede the development of HA. METHODS: We performed a case-control multicenter study. Patients with HA were compared with a control population of 22q11.2DS without HA (non-HA). A complete immunological evaluation was performed at diagnosis and at the last follow-up including extensive T and B phenotypes. RESULTS: Immunophenotype at the last follow-up was available in 23 HA and 45 non-HA patients. HA patients had significantly decreased percentage of naïve CD4+ cells (26.8% vs 43.2%, P = .003) and recent thymic emigrants (48.6% vs 80.5%, P = .046); decreased class-switched B cells (2.0% vs 5.9%, P = .04) and increased naive B cells (83.5% vs 71.4%, P = .02); increased CD16+/56+ both in absolute number (312 vs 199, P = .009) and percentage (20.0% vs 13.0%, P = .03). Immunophenotype was performed in 36 patients (11 HA and 25 non-HA) at diagnosis. Odds ratio (OR) of immune cytopenia were estimated for both CD4 naïve ≤30% (OR 14.0, P = .002) and switched memory B cells ≤2% (OR 44.0, P = .01). The estimated survival curves reached statistical significance, respectively, P = .0001 and P = .002. CONCLUSIONS: Among patients with 22q11.2DS, those with HA have characteristic lymphocyte anomalies that appear considerably before HA onset. Systematic immunophenotyping of patients with 22q11.2DS at diagnosis is advisable for early identification of patients at risk for this severe complication.
BACKGROUND:Patients with 22q11.2 deletion syndrome (22q11.2DS) may develop severe thrombocytopenic purpura and hemolytic anemia. There are no reliable predictors for the development of hematologic autoimmunity (HA) in these patients. OBJECTIVE: To describe the peculiar B and T subpopulation defects in patients with 22q11DS who have developed HA and test if these defects precede the development of HA. METHODS: We performed a case-control multicenter study. Patients with HA were compared with a control population of 22q11.2DS without HA (non-HA). A complete immunological evaluation was performed at diagnosis and at the last follow-up including extensive T and B phenotypes. RESULTS: Immunophenotype at the last follow-up was available in 23 HA and 45 non-HA patients. HA patients had significantly decreased percentage of naïve CD4+ cells (26.8% vs 43.2%, P = .003) and recent thymic emigrants (48.6% vs 80.5%, P = .046); decreased class-switched B cells (2.0% vs 5.9%, P = .04) and increased naive B cells (83.5% vs 71.4%, P = .02); increased CD16+/56+ both in absolute number (312 vs 199, P = .009) and percentage (20.0% vs 13.0%, P = .03). Immunophenotype was performed in 36 patients (11 HA and 25 non-HA) at diagnosis. Odds ratio (OR) of immune cytopenia were estimated for both CD4 naïve ≤30% (OR 14.0, P = .002) and switched memory B cells ≤2% (OR 44.0, P = .01). The estimated survival curves reached statistical significance, respectively, P = .0001 and P = .002. CONCLUSIONS: Among patients with 22q11.2DS, those with HA have characteristic lymphocyte anomalies that appear considerably before HA onset. Systematic immunophenotyping of patients with 22q11.2DS at diagnosis is advisable for early identification of patients at risk for this severe complication.
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Authors: Lucia Leonardi; Beatrice Rivalta; Caterina Cancrini; Elena Chiappini; Claudio Cravidi; Carlo Caffarelli; Sara Manti; Mauro Calvani; Alberto Martelli; Michele Miraglia Del Giudice; Marzia Duse; Gian Luigi Marseglia; Fabio Cardinale Journal: Acta Biomed Date: 2020-09-15
Authors: Francesco Rispoli; Erica Valencic; Martina Girardelli; Alessia Pin; Alessandra Tesser; Elisa Piscianz; Valentina Boz; Flavio Faletra; Giovanni Maria Severini; Andrea Taddio; Alberto Tommasini Journal: Diagnostics (Basel) Date: 2021-03-16