Secondary antibody deficiency

Abstract

Secondary antibody deficiencies are defined by a quantitative or qualitative decrease in antibodies that occur most commonly as a consequence of renal or gastrointestinal immunoglobulin loss, hematological malignancies and corticosteroid, immunosuppressive or anticonvulsant medications. Patients with hematological malignancies or requiring immunosuppressive medications are known to be at increased risk of infection, but few studies directly address this relationship in the context of antibody deficiency. Immunoglobulin replacement therapy has been shown to be effective in reducing infections in primary and some secondary antibody deficiencies. The commonly encountered causes of secondary antibody deficiencies and their association with infection-related morbidity and mortality are discussed. Recommendations are made for screening and clinical management of those at risk.

Keywords::

• antibody
• deficiency
• hypogammaglobulinemia
• immunodeficiency
• immunosuppression
• infection
• rituximab
• secondary

Financial & competing interests disclosure

HJ Longhurst and members of her department have received funding to attend conferences and other educational events, donations to her departmental fund and/or have participated in clinical trials with the following immunoglobulin manufacturers: BPL, CSL Behring, Octapharma, Baxter, Grifols and LFP. She has been a member of the medical advisory panel for Baxter and CSL. S Duraisingham is funded by a grant from CSL Behring. M Buckland has been a medical advisor to Octopharma and received funding for educational events from Octopharma and CSL Behring. S Grigoriadou has been a CI/PI or co-investigator for clinical trials with Baxter, Octapharma, CSL Behring and has received funding for educational events from BPL, Octapharma and CSL Behring. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Secondary antibody deficiency occurs in a proportion of people with hematological malignancies or after certain drug therapies.

• These patients have increased incidence of infections associated with morbidity and mortality.

• Antibody deficiencies, such as hypogammaglobulinemia, specific antibody or subclass deficiencies, are likely to significantly contribute to the occurrence of infections.

• Patients at risk include those with a hematological malignancy, on immunosuppressive medication for autoimmune diseases or allograft transplantation and those on high-dose or frequent corticosteroids for asthma.

• Recommendations are for screening those at risk by measurement of IgG, IgA, IgM and specific pneumococcal antibody levels.

• Treatment recommendations include vaccination (with killed vaccines), microbiological screening, prompt/prolonged antibiotic treatment of infections and investigation of end-organ damage.

• Immunoglobulin replacement therapy is effective in preventing infections in patients with primary and secondary antibody deficiencies, although controversy exists as to when to start treatment.

• Future work aims to delineate the natural history of disease and to identify genetic factors that predispose to development of secondary antibody deficiencies.