Antibody deficiency diseases

Abstract

Primary immunodeficiency diseases are rare disorders characterized by quantitative or qualitative defects in cells or components in the immune system, resulting in a high degree of susceptibility to various types of infections. During differentiation, stem cells undergo a series of discrete steps, governed by a large number of different genes. Mutations/deletions in these genes will result in a block in differentiation of the affected cell lineage(s), leading to immunodeficiency. To date, more than 150 different types of disorders have been described. In this review, we will focus on novel findings in antibody deficiency syndromes. IntroductionPrimary immunodeficiency diseases (PID) are disorders characterized by quantitative or qualitative defects in cells or components in the immune system, resulting in a high degree of susceptibility to various types of infections. During differentiation, stem cells undergo a series of discrete steps, governed by a large number of different genes. Mutations/deletions in these genes will result in a block in differentiation of the affected cell lineage(s), leading to immunodeficiency. To date, more than 150 different types of diseases have been described and the genetic basis for most of these defects is known (see [1,2] for recent reviews).Principally, PID can be subdivided into T cell, B cell, combined (T+B), phagocyte and complement defects. The combined immunodeficiencies (SCID) are clinically the most severe and will, if undiagnosed, lead to death of the affected child, usually within the first year of life. Other defects, numerically more prevalent and including common variable immunodeficiency (CVID) and IgA deficiency (IgAD), will result in considerable morbidity, but are rarely associated with mortality.The above defects are all "global", i.e. associated with susceptibility to a variety of different pathogens. However, recently, several PID have been described that are characterized by an increased frequency of infections caused by selected pathogens such as mycobacteria, pneumococci [3] and herpes simplex virus [4,5]. Such "holes-in-the-repertoire" defects (for recent review see [6]) are likely to be common in the population and may, taken together, account for a substantial number of, hitherto largely undiagnosed, patients with PID. Furthermore, a recent observation [7] shows that novel mutations in "classical" genes, i.e. those known to be involved in a given PID, may give rise to a different phenotype, suggesting that the field is getting more complex than previously recognized. In addition, the etiology of several phenotypically similar, albeit in some cases not entirely identical, PID have recently been shown to be caused by mutations in other genes than those originally implicated (examples include hyper-IgM (HIGM, see below), X-linked lymphoproliferative syndrome [8], hyper-IgE [9, 10], Omenn syndrome [11] and X-linked susceptibility to mycobacterial infections [12]. Differences in glycosylation pattern may also account for selected disease phenotypes [13] and...

Selective IgA Deficiency in Autoimmune Diseases

“…Selective immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency with a frequency of 1 in 600 in Caucasians (1). The prevalence in various ethnic groups ranges from 1:155 in Spain (2) to 1:18,550 in Japan (3) (for additional data, see refs.…”

B-cell maturation and antibody responses in individuals carrying a mutated CD19 allele

“…1,2 Consequently, the patients are highly susceptible to infections with encapsulated bacteria, and can have a high incidence of bronchitis and pneumonia, which often lead to progressive and irreversible lung damage. Initial diagnosis and subdivision into three categories is based on the reduction of serum immunoglobulin (Ig) levels in combination with the number of B cells in peripheral blood: 1,2 (1) patients with strongly reduced B-cell numbers and serum Ig levels are defined as agammaglobulinemic; (2) patients with normal B-cell numbers, normal to high IgM, but severely reduced IgG and IgA suffer from a Hyper-IgM syndrome; and (3) patients with low to normal B-cell numbers and strongly reduced IgG, and IgA or IgM are diagnosed with a 'common variable immunodeficiency disorder' (CVID). In the last two decades, multiple gene defects have been identified that underlie these types of antibody deficiencies.…”

Helicobacter pylori infection in patients with selective immunoglobulin a deficiency

“…IgA deficiency (IgAD) is the most common primary immunodeficiency in the western world [1], with prevalence rates ranging from 1 : 155 in Spain [2] to 1 : 18 550 in Japan [3]. In Israel IgAD prevalence is approximately 1 : 500-600 in the general population [1].…”

“…In Israel IgAD prevalence is approximately 1 : 500-600 in the general population [1]. The current definition, established by the Pan-American Group for Immunodeficiency and the European Society for Immunodeficiencies, defines the disorder as serum IgA levels < 0Á07 g/l with normal IgM and IgG levels in individuals !…”