Abstract
Although selective IgM deficiency (SIGMD) was described almost five decades ago, it was largely ignored as a primary immunodeficiency. SIGMD is defined as serum IgM levels below two SD of mean with normal serum IgG and IgA. It appears to be more common than originally realized. SIGMD is observed in both children and adults. Patients with SIGMD may be asymptomatic; however, approximately 80% of patients with SIGMD present with infections with bacteria, viruses, fungi, and protozoa. There is an increased frequency of allergic and autoimmune diseases in SIGMD. A number of B cell subset abnormalities have been reported and impaired specific antibodies to Streptococcus pneumoniae responses are observed in more than 45% of cases. Innate immunity, T cells, T cell subsets, and T cell functions are essentially normal. The pathogenesis of SIGMD remains unclear. Mice selectively deficient in secreted IgM are also unable to control infections from bacterial, viral, and fungal pathogens, and develop autoimmunity. Immunological and clinical similarities and differences between mouse models of deficiency of secreted IgM and humans with SIGMD have been discussed. Patients with SIGMD presenting with recurrent infections and specific antibody deficiency responses appear to improve clinically on immunoglobulin therapy.
Highlights
IgM is the first immunoglobulin to be expressed on the surface of B cells [1], and the first immunoglobulin isotype secreted during an initial immune response to an exogenous antigen
It appears that the specificity to bind to components of self-antigen is critical for protecting effect of natural IgM against autoimmunity
A significant increase in CD21low, and IgM memory B cells, and a significant decreased in germinal center (GC) B cells, and CXCR3+ naïve and memory B cells were observed in selective IgM deficiency (SIGMD)
Summary
IgM is the first immunoglobulin to be expressed on the surface of B cells [1], and the first immunoglobulin isotype secreted during an initial immune response to an exogenous antigen. The majority of circulating IgM is comprised of natural IgM antibodies It has been established from studies of mutant mice deficient in IgM secretion that both natural and immune IgM are important in responses to pathogens and selfantigens [4, 5]. In addition to providing early defense against microbes, natural IgM plays an important role in immune homeostasis, and provide protection from consequences of autoimmunity and inflammation [6,7,8,9]. It appears that the specificity to bind to components of self-antigen is critical for protecting effect of natural IgM against autoimmunity. The immune IgM antibodies are selected for antigen-specificity that are usually produced in response to pathogens, and serve as a first line of defense against microbial infections and provide protection from autoimmune diseases [4, 6]. The most common association of SIGMD has been with 22q11.2 deletion syndrome [18,19,20, 23,24,25]
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