The Expanding Field of Secondary Antibody Deficiency: Causes, Diagnosis, and Management

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.

Peripheral Blood Lymphocyte Phenotype Differentiates Secondary Antibody Deficiency in Rheumatic Disease from Primary Antibody Deficiency

“…A common side effect of anti-inflammatory regimens including corticosteroids, DMARD and biologics is hypogammaglobulinemia, which sometimes associates with clinically evident immunodeficiency [1,2]. In the present study approximately 20% of patients with secondary hypogammaglobulinemia displayed recurrent infections and were treated with immunoglobulin replacement.…”

“…Hypogammaglobulinemia as a consequence of hematological malignancies, systemic disorders causing excessive loss or catabolism of immunoglobulins, viral infections or drugs, such as antiepileptic agents and anti-inflammatory medications, is defined as secondary hypogammaglobulinemia [1,2]. Its exclusion is required for the diagnosis of primary immunodeficiency disorders (PID) [3].…”

“…Secondary hypogammaglobulinemia is distinguished from primary hypogammaglobulinemia on the basis of a patient's medical history [2,3]. In other words, the diagnosis of a PID is clear in case the diagnosis of hypogammaglobulinemia precedes immunosuppressive treatment of autoimmune or lymphoproliferative conditions.…”

Management of children with primary and secondary hypogammaglobulinemia (literature review)

“…Доза встановлюється індивіду ально, але в середньому становить 0,2-0,4 г/кг кожні 3-4 тижні. [24] Опубліковані дані щодо лікування хворих із вторинною гіпогаммагло булінемією, які охоплюють широкий діапазон дозування препаратів підшкірного імуноглобу ліну від 50 до 200 мг/кг/тиждень [36]. Прове дення замісної терапії препаратами підшкірно го імуноглобуліну рекомендовано у пацієнтів із множинною мієломою та хронічною лімфо цитарною лейкемією за наявності інфекційного синдрому та неефективності проведеної анти біотикопрофілактики, а також до та після про ведення алогенної трансплантації кісткового мозку.…”

Defining B-cell defects and correlation with complications in patients with common variable immune deficiency

“…6 Not only important for PADs, this method will also be useful in dissecting secondary antibody failures and might help distinguish those patients needing long-term therapeutic immunoglobulin and those who will recover antibody production in due course (Table I). 7 The purpose of this research was to delineate the varied defects in antibody production. Blood samples from 139 patients, 61 with CVID, 68 with SIgAD, and 10 with IgG subclass deficiencies with IgA deficiency, were tested, along with those from 223 agematched control subjects.…”