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Iatrogenic antibody deficiency from B-cell targeted therapies in autoimmune rheumatic diseases
  1. Sonali Wijetilleka1,
  2. David Jayne2,
  3. Chetan Mukhtyar3 and
  4. Mohammed Yousuf Karim4
  1. 1Immunology, University Hospital of Wales, Cardiff, Cardiff, UK
  2. 2Department of Medicine, University of Cambridge, Cambridge, UK
  3. 3Rheumatology, Norfolk and Norwich University Hospital, Norwich, UK
  4. 4Pathology, Sidra Medical and Research Center, Doha, Qatar
  1. Correspondence to Dr Mohammed Yousuf Karim; mkarim{at}


B-cell targeted therapies (BCTT) are now widely used in autoimmune rheumatic diseases, including SLE, antineutrophil cytoplasmic antibody-associated vasculitis and rheumatoid arthritis. Early studies suggested that rituximab did not influence serum immunoglobulins. However, subsequently, with increased patient numbers, longer follow-up duration and many patients having received multiple BCTT courses, multiple subsequent studies have identified hypogammaglobulinaemia as a potential side effect. Patients developing hypogammaglobulinaemia appear to fit into two principal categories: the majority who develop transient, often mild reduction in immunoglobulins without increased infection and a much smaller but clinically significant group with a more sustained antibody deficiency, who display increased risk of infection. Monitoring immunoglobulin levels represents an opportunity for the early detection of hypogammaglobulinaemia, and the prevention of avoidable morbidity. In the two major studies, approximately 4%–5% of BCTT-treated patients required immunoglobulin replacement due to recurrent infections in the context of hypogammaglobulinaemia. Despite this, monitoring of immunoglobulins is suboptimal, and there remains a lack of awareness of hypogammaglobulinaemia as an important side effect.

  • B-cell
  • rituximab
  • hypogammaglobulinaemia
  • antibody deficiency
  • immunoglobulin replacement
  • immunodeficiency
  • lupus
  • vasculitis

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  • Contributors All authors contributed to this project in article concept and planning, manuscript writing, expert critical review of manuscript and manuscript editing. All authors read and approved the final manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests DJ has received research grants from Roche/Genentech. From August 2017 to February 2018, SW was a Clinical Research Fellow supported by an unrestricted grant from Roche Products (UK) to undertake a Systematic Literature Review on hypogammaglobulinaemia after B-cell targeted therapies. MYK, CM and DJ were co-applicants on that grant (grant number GDRC-FEB-001-2017).

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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