Abstract
Antibody deficiency or hypogammaglobulinemia can have primary or secondary etiologies. Primary antibody deficiency (PAD) is the result of intrinsic genetic defects, whereas secondary antibody deficiency may arise as a consequence of underlying conditions or medication use. On a global level, malnutrition, HIV, and malaria are major causes of secondary immunodeficiency. In this review we consider secondary antibody deficiency, for which common causes include hematological malignancies, such as chronic lymphocytic leukemia or multiple myeloma, and their treatment, protein-losing states, and side effects of a number of immunosuppressive agents and procedures involved in solid organ transplantation. Secondary antibody deficiency is not only much more common than PAD, but is also being increasingly recognized with the wider and more prolonged use of a growing list of agents targeting B cells. SAD may thus present to a broad range of specialties and is associated with an increased risk of infection. Early diagnosis and intervention is key to avoiding morbidity and mortality. Optimizing treatment requires careful clinical and laboratory assessment and may involve close monitoring of risk parameters, vaccination, antibiotic strategies, and in some patients, immunoglobulin replacement therapy (IgRT). This review discusses the rapidly evolving list of underlying causes of secondary antibody deficiency, specifically focusing on therapies targeting B cells, alongside recent advances in screening, biomarkers of risk for the development of secondary antibody deficiency, diagnosis, monitoring, and management.
Highlights
Antibody deficiencies, a subset of immunodeficiencies, are classified as primary or secondary in etiology
This study reported a 4.8-fold increase in respiratory infections, a 2.4-fold increase in CMV infections, and an 8fold increase in aspergillus infections (3.7-fold increase in other fungal infections) when severe hypogammaglobulinemia was present [124]
Secondary antibody deficiency is defined as “Hypogammaglobulinemia secondary to underlying disease or medical therapy with all of the following: Serum immunoglobulin G (IgG) less than the lower limit of the reference range on two separate occasions AND at least one of the following: a) one invasive or life-threatening bacterial infection in the previous year; b) recurrent, severe bacterial infections; c) Clinically active bronchiectasis confirmed by radiology or d) assessment by a physician specializing in immunodeficiency indicating a significant antibody defect that would benefit from immunoglobulin replacement” [232]
Summary
A subset of immunodeficiencies, are classified as primary or secondary in etiology. Retrospective studies have demonstrated that addition of IVIG to antimicrobial therapy in heart transplantation recipients with secondary antibody deficiency and severe infections is associated with reconstitution of specific antibodies (anti-CMV, anti-tetanus toxoid) and lower rates of death [183, 225].
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