Hapten Antibody Production and the Relevance of Allogeneic Reactions to Elimination of the Carrier Effect

Lewis (LEW) rats immunized 3 weeks before by injection of DNP-KLH together with &lt;i&gt;Bordetella pertussis&lt;/i&gt; showed high levels of DNP antibody as judged by serum binding of 10&lt;sup&gt;––7&lt;/sup&gt;&lt;i&gt;M&lt;/i&gt;&lt;sup&gt;3&lt;/sup&gt;H-DNP-lysine 10 days after secondary immunization with DNP-KLH. Sera obtained from LEW rats following secondary immunization with DNP-BGG showed reduced DNP hapten binding. However, injection of 10&lt;sup&gt;8&lt;/sup&gt; F&lt;sub&gt;1&lt;/sub&gt; hybrid Lewis × Brown Norway spleen cells into DNP-primed LEW rats 2 days before secondary immunization with DNP-BGG significantly increased the level of serum binding of &lt;sup&gt;3&lt;/sup&gt;H-DNP-lysine. These results provide evidence that the allogeneic cellular reaction associated with a host-versus-graft response induced by injection of F&lt;sub&gt;1&lt;/sub&gt; hybrid lymphoid cells into DNP-primed parental strain recipients partially obviates the requirement for carrier-specific T cells in the secondary anti-DNP response thereby providing a stimulus for triggering primed host B cells to produce antibody.</jats:p

Human Serum Antibodies Reactive with Dietary Proteins

The antigenic specificity of human serum IgG antibodies reactive with common dietary proteins has been evaluated by competitive binding using a solid-phase immunoassay (ELISA). Antibodies reactive with bovine milk antigens were shown to be reactive predominantly with casein, rather than α-lactalbumin, β-lactoglobulin, γ-globulin or albumin. Furthermore, sera containing antibodies reactive with bovine casein, wheat gliadin and chicken ovalbumin showed competitive binding only by each respective dietary protein antigen. IgG4 antibodies specifically reactive with ovalbumin, gliadin or casein were also not cross-reactive in competitive binding studies. Furthermore, both IgG2 and IgG4 anti-milk antibodies showed significant inhibition only with bovine casein, and not with α-lactalbumin or β-lactoglobulin. These data are relevant to concepts regarding the immunobiological role of antibodies of the IgG4 isotype.</jats:p

IgG Subclass of Human Serum Antibodies Reactive with Dietary Proteins

Serum IgG antibodies reactive with different dietary proteins have been detected in a significant proportion of adult patients with coeliac disease, dermatitis herpetiformis and atopic eczema. Serum anti-milk antibodies were shown to be distributed predominantly between the IgG2 and IgG4 subclasses, whereas anti-gliadin antibodies in atopic eczema were predominantly of the IgG4 subclass. Furthermore, as antibodies to each of these dietary antigens in healthy adults were markedly restricted to the IgG4 subclass, their production may be part of a normal immune response to dietary proteins. There was no correlation between serum IgG4 antibody and total serum IgG4 level. In contrast, restricted IgG4 anti-gliadin antibodies were less prevalent in the serum of patients with coeliac disease and dermatitis herpetiformis, suggesting defective downstream switching of Ig heavy-chain genes in these conditions.</jats:p

Human Serum Antibodies Reactive with Dietary Proteins

The isotype distribution of human IgG antibodies reactive with common dietary proteins has been evaluated in sera from adult patients with the irritable bowel syndrome and with bronchial asthma using a solid-phase immunoassay (ELISA). In both these medical disorders, serum antibodies reactive with ovalbumin or gliadin were restricted predominantly to the IgG4 isotype; however, IgG antibodies reactive with bovine milk antigens, notably casein, were often restricted to both the IgG2 and IgG4 isotypes. A similar serum IgG antibody isotype distribution for these dietary protein antigens was also demonstrated in IgG antibody-positive healthy adults. These data amplify the view that production of antibodies of the IgG4 isotype may reflect a normal immune response to dietary protein antigens presented at mucosal surfaces.</jats:p

Serum Antibodies Reactive with &lt;i&gt;Saccharomyces cerevisiae&lt;/i&gt; in Inflammatory Bowel Disease: Is IgA Antibody a Marker for Crohn’s Disease?

Sera from patients with Crohn’s disease (CD) and ulcerative colitis (UC) have been evaluated for antibodies reactive with &lt;i&gt;Saccharomyces cerevisiae &lt;/i&gt;(anti-Sacc antibodies) using an enzyme-linked immunoassay (ELISA). IgG anti-Sacc antibodies were detected in 63% (25/40) of CD patients, compared with 15% (4/27) of UC patients (p &lt;0.001) and 8% (5/60) healthy adult controls (p &lt;0.001). Furthermore, the prevalence of detectable IgG anti-Sacc antibodies in adult patients with coeliac disease, dermatitis herpetiformis, irritable bowel syndrome or atopic eczema was not significantly different to controls. In comparison, the prevalence of detectable IgG anti-&lt;i&gt;Escherichia coli &lt;/i&gt;antibodies was not significantly different between CD (75%) or UC (79%) patients. More particularly, elevated levels of serum IgA anti-Sacc antibodies were detected in 17/40 CD patients, but in none of the 27 UC patients. These data confirm that serum antibodies reactive with &lt;i&gt;S. cerevisiae &lt;/i&gt;are strongly associated with CD and further show that serum IgA anti-Sacc antibodies may be specific for this disorder.</jats:p