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Current Spectrum of Infections in Patients with X-Linked Agammaglobulinemia

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Abstract

Outcome of patients with X-linked agammaglobulinemia (XLA) has improved with the widespread use of immunoglobulin replacement therapy (IgRT). There are few data on the spectrum of infections experienced by patients undergoing IgRT. We carried out a retrospective cross-sectional analysis of the records of XLA patients seen at Necker-Enfants Malades Hospital, Paris. For each infection, we evaluated infection site, microbial etiology, antibiotic prophylaxis, immunosuppressive treatment, IgRT route, and last known IgG trough level. Sixty patients were included, who cumulated a follow-up of 1470 patient-years. We recorded 188 infections, including 97 after initiation of IgRT. The rate of infection was highest before IgRT (0.66 vs. 0.06 per person-year (ppy), p < 0.001) and was higher after the age of 16 compared to before (0.14 vs. 0.05 ppy, p = 0.048). It was similar for patients receiving intravenous or subcutaneous Ig (0.09 vs 0.05 ppy, p = 0.54). The lungs and gastrointestinal tract accounted for 71% of infection sites. Forty-six (47%) infections occurred in patients receiving antibiotic prophylaxis. Sixteen (16.5%) infections occurred in patients receiving immunosuppressive therapy, which more frequently occurred after age 16 (35% vs. 2.4%, p < 0.001). The median IgG trough level prior to all infections was 8.4 g/L. Almost half (44.3%) of infections occurred with prior IgG trough levels > 8 g/L, and 16/97 (16.7%) in patients with trough levels > 10 g/L. Infection remains a significant issue in patients with XLA undergoing IgRT despite adequate IgG trough levels. Chronic inflammatory manifestations of X-linked agammaglobulinemia and immunosuppressive therapies may be significant drivers of infection during adulthood.

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Author notes

  1. Nizar Mahlaoui, Despina Moshous, Olivier Hermine, and Olivier Lortholary contributed equally to this work.

Authors and Affiliations

  1. Necker-Pasteur Center for Infectious Diseases and Tropical Medicine, Necker-Enfants Malades University Hospital, Assistance Publique des Hôpitaux de Paris (AP-HP), Université de Paris, 149 Rue de Sèvres, 75015, Paris, France

    Olivier Paccoud, Claire Aguilar, Fanny Lanternier, Marc Lecuit & Olivier Lortholary

  2. Pediatric Immuno-Hematology and Rheumatology Unit, Necker-Enfants Malades University Hospital, AP-HP, Université de Paris, Paris, France

    Nizar Mahlaoui, Despina Moshous, Bénédicte Neven, Alain Fischer & Stéphane Blanche

  3. Imagine Institute, INSERM UMR1163, Université de Paris, Paris, France

    Nizar Mahlaoui, Despina Moshous, Claire Aguilar, Bénédicte Neven, Felipe Suarez, Capucine Picard, Alain Fischer, Stéphane Blanche, Marc Lecuit, Olivier Hermine & Olivier Lortholary

  4. French National Reference Center for Primary Immune Deficiencies (CEREDIH), Necker-Enfants Malades University Hospital, AP-HP, Paris, France

    Nizar Mahlaoui, Despina Moshous, Bénédicte Neven, Felipe Suarez, Capucine Picard, Alain Fischer, Stéphane Blanche & Olivier Hermine

  5. Department of Hematology, Necker-Enfants Malades University Hospital, AP-HP, Université de Paris, Paris, France

    Felipe Suarez & Olivier Hermine

  6. Study Center for Primary Immunodeficiencies (CEDI), Necker-Enfants Malades University Hospital, AP-HP, Paris, France

    Capucine Picard

  7. Biology of Infection Unit, Inserm U1117, Pasteur Institute, Paris, France

    Marc Lecuit

Authors
  1. Olivier Paccoud
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  2. Nizar Mahlaoui
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  3. Despina Moshous
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  4. Claire Aguilar
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  5. Bénédicte Neven
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  6. Fanny Lanternier
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  7. Felipe Suarez
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  8. Capucine Picard
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  9. Alain Fischer
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  10. Stéphane Blanche
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  11. Marc Lecuit
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  12. Olivier Hermine
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Correspondence to Olivier Paccoud.

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Paccoud, O., Mahlaoui, N., Moshous, D. et al. Current Spectrum of Infections in Patients with X-Linked Agammaglobulinemia. J Clin Immunol 41, 1266–1271 (2021). https://doi.org/10.1007/s10875-021-01043-1

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  • DOI: https://doi.org/10.1007/s10875-021-01043-1

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