Primary antibody deficiency syndromes

Abstract

The primary antibody deficiency syndromes are a group of rare disorders characterized by an inability to produce clinically effective immunoglobulin responses. Some of these disorders result from genetic mutations in genes involved in B cell development, whereas others appear to be complex polygenic disorders. They most commonly present with recurrent infections due to encapsulated bacteria, although in the most common antibody deficiency, Common Variable Immunodeficiency, systemic and organ-specific autoimmunity can be a presenting feature. Diagnostic delay in this group of disorders remains a problem, and the laboratory has a vital role in the detection of abnormalities in immunoglobulin concentration and function. It is critical to distinguish this group of disorders from secondary causes of hypogammaglobulinaemia, in particular lymphoid malignancy, and appropriate laboratory investigations are of critical importance. Treatment of primary antibody deficiencies involves immunoglobulin replacement therapy, either via the intravenous or subcutaneous route. Patients remain at risk of a wide variety of complications, not all linked to diagnostic delay and inadequate therapy. In common variable immunodeficiency (CVID) in particular, patients remain at significantly increased risk of lymphoid malignancy, and regular clinical and laboratory monitoring is required. This review aims to give an overview of these conditions for the general reader, covering pathogenesis, clinical presentation, laboratory investigation, therapy and clinical management.

What Are the Characteristics of the Upper Airway in Patients With Craniofacial Microsomia?

“…Predominantly antibody deficiencies (PADs) are the most prevalent primary immunodeficiencies (50% to 70% of all primary immunodeficiencies) 1,2 and comprise a heterogeneous spectrum of disorders with defective production of 1 or more immunoglobulin isotypes and/or immunoglobulin subclasses; the underlying pathogenic mechanisms remain largely unknown. 1,2 Current classification of PADs strongly relies on the affected serum immunoglobulin heavy chain (IgH) isotype and subclass levels and includes (1) selective IgA deficiency (IgAdef) characterized by an isolated defect of serum IgA (prevalence, approximately 1:100-1,000 subjects) [3][4][5] ; (2) IgG subclass deficiency with IgA deficiency (IgG/Adef) with reduced IgA and 1 or more IgG subclass serum levels (approximately 15% to 20% of IgA deficiencies) 6 ; and (3) common variable immunodeficiency (CVID), which is characterized by low (total) IgG serum levels, decreased IgA and/or IgM levels, and a more severe clinical presentation but a lower prevalence (approximately 1:25,000-50,000 subjects). 4,5 Although recurrent bacterial infections of the respiratory tract are the clinical hallmark of PADs, clinical manifestations vary substantially among patients, from (almost) asymptomatic cases to patients presenting with recurrent severe infections associated with other noninfectious disorders, such as autoimmunity, allergy, lymphoproliferation and organomegalies, enteropathy, and granulomatous disease.…”

“…1,3,[7][8][9][10] Despite extensive efforts, genetic (ie, monogenic) alterations responsible for PADs are detected in less than 10% of cases. 1,2,11 In such settings altered distributions of distinct blood B-and Tcell subpopulations determined by using flow cytometry might provide key (complementary) diagnostic information, particularly for patients with low serum antibody isotype levels and nonspecific clinical features. 5,12,13 Thus controversial results have been reported in patients with CVID concerning the potential association between specific B-cell alterations, such as decreased (relative) numbers of CD27 1 (antigen-experienced) switched B cells in blood and relevant clinical manifestations (eg, splenomegaly, granulomatous disease, and autoimmunity), [14][15][16][17][18] whereas preservation of CD27 1 class-switched memory B cells (MBCs) has been considered a surrogate marker for the ability to respond to vaccination.…”

Infection outcomes in patients with common variable immunodeficiency disorders: Relationship to immunoglobulin therapy over 22 years

“…1 Replacement immunoglobulin is the standard treatment for patients with CVIDs, with intravenous and subcutaneous routes replacing the painful and less effective intramuscular route. 2 Despite the ability to administer larger doses by the intravenous and subcutaneous routes, some patients remain susceptible to acute breakthrough and chronic infections as well as a myriad of noninfectious complications. 3 The efficacy of replacement therapy was evidenced by studies of infection prevention that resulted in raising serum trough IgG levels and reducing rates of severe and moderate infections.…”

Human normal immunoglobulin in the treatment of primary immunodeficiency diseases

“…Skin infections may be fungal, bacterial, or viral 46. Patients with primary antibody deficiencies on immunoglobulin therapy remain at risk of a number of organ-specific and systemic complications, including inflammatory bowel disease, neurodegeneration, and malignancy 47.…”