Abstract
Patients with primary immunoglobulin deficiency have lower immunoglobulin levels or decreased immunoglobulin function, which makes these patients more susceptible to bacterial infection. Most prevalent are the selective IgA deficiencies (~1:3,000), followed by common variable immune deficiency (~1:25,000). Agammaglobulinemia is less common (~1:400,000) and is characterized by very low or no immunoglobulin production resulting in a more severe disease phenotype. Therapy for patients with agammaglobulinemia mainly relies on prophylactic antibiotics and the use of IgG replacement therapy, which successfully reduces the frequency of invasive bacterial infections. Currently used immunoglobulin preparations contain only IgG. As a result, concurrent IgA and IgM deficiency persist in a large proportion of agammaglobulinemia patients. Especially patients with IgM deficiency remain at risk for recurrent infections at mucosal surfaces, which includes the respiratory tract. IgA and IgM have multiple functions in the protection against bacterial infections at the mucosal surface. Because of their multimeric structure, both IgA and IgM are able to agglutinate bacteria efficiently. Agglutination allows for entrapment of bacteria in mucus that increases clearance from the respiratory tract. IgA is also important for blocking bacterial adhesion by interfering with bacterial adhesion receptors. IgM in its place is very well capable of activating complement, therefore, it is thought to be important in complement-mediated protection at the mucosal surface. The purpose of this Mini Review is to highlight the latest advances regarding IgA- and IgM-enriched immunoglobulin replacement therapy. We describe the different IgA- and IgM-enriched IgG formulations, their possible modes of action and potential to protect against respiratory tract infections in patients with primary immunoglobulin deficiencies.
Highlights
ROLE FOR IMMUNOGLOBULIN SUBCLASSES IN PROTECTION AGAINST BACTERIAL INFECTIONSImmunoglobulin production by B-lymphocytes is a sophisticated adaptive immune defense mechanisms evolved in jawed vertebrates [1]
Specialty section: This article was submitted to Microbial Immunology, a section of the journal Frontiers in Immunology
We describe the different IgA- and IgM-enriched IgG formulations, their possible modes of action and potential to protect against respiratory tract infections in patients with primary immunoglobulin deficiencies
Summary
Immunoglobulin production by B-lymphocytes is a sophisticated adaptive immune defense mechanisms evolved in jawed vertebrates [1]. The different immunoglobulins have specific functions in immunity Upon binding to their targets, both IgG and IgM are capable of activating complement through binding of C1q. Recent data indicate that IgG oligomerizes into hexamers, forming an optimal configuration for C1q binding [10] This oligomerization might explain the more efficient activation of complement by IgM, [11,12,13] because it is present as polymeric structures (pIgM) [14]. IgA and IgM can be transported to mucosal surfaces through the polymeric immunoglobulin receptor (pIgR) [20]. Vaccine-induced polysaccharide capsule-specific antibodies initiate complement deposition on the bacterial surface, which is essential for opsonophagocytic killing of S. pneumoniae and H. influenzae in whole blood [40]
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