Gastrointestinal manifestations of common variable immunodeficiency

Gastrointestinal manifestations of common variable immunodeficiency. and a generalized failure of maturation of IgM-bearing lymphocytes into IgA-secreting plasma cells. IgA-deficient subjects have low but detectable numbers of circulating IgA B cells, but these may have a relatively immature phenotype, bearing both IgA and IgM isotypes (Conley and Cooper, 1981). Another consistent feature is a general paucity of IgA-bearing plasma cells in the RG7112 intestinal tract (Crabb and Heremans, 1967). In a number of early studies, B cells from IgA-deficient subjects were cultured with mitogens to determine their ability to secrete IgA; in most cases, little if any IgA was produced (Luzi (1994), showed Vezf1 that pokeweed mitogenCstimulated peripheral blood lymphocytes of IgA-deficient subjects have a significant decrease in switch – to switch -junctions and a profound decrease in C membrane mRNA expression, suggesting a generalized failure of switching to IgA production. Two types of defects, low expression of both secreted and membrane forms of productive C mRNA in IgA-switched B cells and impaired IgA switching, were characterized in IgA-deficient subjects homozygous for the common major histocompatibility complex (MHC) haplotype (HLA-B8, SC01, DR3). This could reflect a blockade in post-IgA switch differentiation of B cells (Wang and IL-10; while IL-10 was not absolutely required for IgA secretion for B cells of normal donors, for IgA-deficient RG7112 subjects it appeared necessary for IgA secretion (Briere (1994) found no difference in TGF- mRNA in IgA-deficient individuals compared with controls. In another study, mitogen-stimulated mononuclear cells of IgA-deficient patients with the common MHC haplotype HLA-B8, -DR3 had significantly reduced IL-5 production (Lio 1998). For example, fucose, linked 1-2 to galactose on the SC N-glycans, competes with for binding to gastric receptors (Falk, (Wold, (Dallas and Rolfe 1998), and both free and S-IgA-bound SC interacts specifically with a surface protein of (Hammerschmidt 1997; Zhang which expresses a mannose-specific lectin (Wold b Rotavirus Poliovirus Echovirus Coxsackievirus Respiratory syncytial virus Influenza Arbovirus Semliki Rose River Japanese B Dengue Mumps Human immunodeficiency virus Herpes simplex Herpes zoster Coronavirus Rubella Cytomegalovirus (Arnold (1986) attempted to relate the number of respiratory tract infections in IgA-deficient subjects to the level of IgM in saliva, hypothesizing that an inverse relationship was likely to be present. These studies showed that there was no such relationship. Norhagen and associates RG7112 (1989) have also questioned the look at that IgM can compensate for IgA deficiency, since they could not relate salivary IgM levels to health or rate of recurrence of illness in 63 IgA-deficient subjects. However, Fernandes (1995) found that IgA-deficient children with increased levels RG7112 of salivary antiof the IgM isotype experienced fewer dental care caries, suggesting a protective part for this antibody. In addition, S-IgM antibodies may be intrinsically less biologically efficient, resulting, for example, in more long term excretion of vaccine viruses than seen in normal subjects (Savilahti (1993a) analyzed IgA-deficient subjects with and without IgG2 deficiency to determine the isotype of this response; after oral cholera vaccination, these individuals experienced an increased quantity of IgG1-generating intestinal B cells. Even though IgG-secreting mucosal cells might be important in local immunity in IgA deficiency, match activation by immune complexCassociated IgG could lead to unregulated mucosal swelling. One would presume that the compensatory mechanisms of the intestinal tract in IgA deficiency would be related in the respiratory tract, but this seems not to become the case; in the top airway at least, IgA-deficient subjects may have a large number of IgD-producing cells (Brandtzaeg (1995) found that IgA-deficient and control subjects experienced the same quantity of T cells, whereas Nilssen (1993b) found that healthy IgA-deficient subjects appeared to possess an increased quantity of T cells. Improved numbers of triggered IELs in IgA deficiency might serve as a useful check on lymphocyte proliferation and/or the amount of local antibody produced. IgA-deficient individuals with celiac disease given gluten have a further increase in the number of CD8+ T cells in the epithelial compartment (Klemola occur with increased rate of recurrence in the absence of IgA. Even though part of S-IgA in resistance to in normal subjects RG7112 is not proved, the fact that IgA-deficient subjects of a wide age range have no higher than expected incidence of infections and the same levels of serum titers to suggests that S-IgA takes on a relatively small part in mucosal safety against this microbe (Bogstedt rotavirus, bacterial overgrowthInflammatoryNodular.