Rituximab Unveils Hypogammaglobulinemia and Immunodeficiency in Children with Autoimmune Cytopenia

Giorgio Ottaviano, Maddalena Marinoni, Simona Graziani, Keith Sibson, Federica Barzaghi, Patrizia Bertolini, Loredana Chini, Paola Corti, Caterina Cancrini, Irene D'Alba, Maria Gabelli, Vera Gallo, Carmela Giancotta, Paola Giordano, Giuseppe Lassandro, Baldassare Martire, Rosa Angarano, Elena Mastrodicasa, Cecilia Bava, Maurizio MianoSamuele Naviglio, Federico Verzegnassi, Paola Saracco, Antonino Trizzino, Andrea Biondi, Claudio Pignata, Viviana Moschese

Research output: Contribution to journalArticlepeer-review


Background: Rituximab (RTX; anti-CD20 mAb) is a treatment option in children with refractory immune thrombocytopenia, autoimmune hemolytic anemia (AHA), and Evans syndrome (ES). Prevalence and clinical course of RTX-induced hypogammaglobulinemia in these patients are poorly known. Objective: To evaluate the prevalence and risk factors for persistent hypogammaglobulinemia (PH) after RTX use. Methods: Clinical and immunologic data from children treated with RTX for immune thrombocytopenia, AHA, and ES were collected from 16 Italian centers and 1 UK center at pre-RTX time point (0), +6 months, and yearly, up to 4 years post-RTX. Patients with previously diagnosed malignancy or primary immune deficiency (PID) were excluded. Results: We analyzed 53 children treated with RTX for immune thrombocytopenia (n = 36), AHA (n = 13), and ES (n = 4). Median follow-up was 30 months (range, 12-48). Thirty-two percent of patients (17 of 53) experienced PH, defined as IgG levels less than 2 SD for age at last follow-up (>12 months after RTX). Significantly delayed B-cell recovery was observed in children experiencing PH (hazard ratio, 0.55; P <.05), and 6 of 17 (35%) patients had unresolved B-cell lymphopenia at last follow-up. PH was associated with IgA and IgM deficiency, younger age at RTX use (51 vs 116 months; P <.01), a diagnosis of AHA/ES, and better response to RTX. Nine patients with PH (9 of 17 [53%]) were eventually diagnosed with a PID. Conclusions: Post-RTX PH is a frequent condition in children with autoimmune cytopenia; a sizable proportion of patients with post-RTX PH were eventually diagnosed with a PID. In-depth investigation for PID is therefore recommended in these patients.

Original languageEnglish
Pages (from-to)273-282
Number of pages10
JournalJournal of Allergy and Clinical Immunology: In Practice
Issue number1
Publication statusPublished - Jan 2020


  • Autoimmunity
  • Cytopenia
  • Hypogammaglobulinemia
  • Primary immunodeficiency
  • Rituximab

ASJC Scopus subject areas

  • Immunology and Allergy


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