Naturally occurring antibodies/autoantibodies in polyclonal immunoglobulin concentrates

It was a long way from the use of hyperimmune animal sera for the treatment of toxin-producing infections to the production of polyclonal, polyspecific human immunoglobulin preparations and the use of NAbs as therapeutic tools for autoimmune and inflammatory diseases. Some highlights of the development of knowledge in blood fractionation techniques, basic science and clinical wisdom are reviewed in this chapter. Proudly we mention the outstanding contribution of Swiss scientists and clinicians in the development of IVIG as clinical tool for some otherwise untreatable diseases or taking advantage of its low adverse event profile in long-term treatment of other chronic autoimmune and inflammatory diseases. This chapter summarizes some of the characteristics and the effects in humans of NAbs which are present in IgG concentrates. We call attention to the fact that the human data remain, at least in part, incomplete, among others because even with the most efficient large-scale techniques available not more than approximately 50% of the total IgG in plasma can be fractionated into an immunoglobulin G concentrate.

Production of monoclonal antibodies specific for native equine IgE and their application to monitor total serum IgE responses in Icelandic and non-Icelandic horses with insect bite dermal hypersensitivity

Immunoglobulin E forms a minor component of serum antibody in mammals. In tissues IgE is bound by FcvarepsilonRI receptors on the surface of mast cells and mediates their release of inflammatory substances in response to antigen. IgE and mast cells have a central role in immunity to parasites and the pathogenesis of allergic diseases in horses and other mammals. This paper describes the production of several novel monoclonal antibodies that detect native equine IgE in immunohistology, ELISA and Western blotting. An antigen capture ELISA to quantify equine IgE in serum has been developed using two of these antibodies. The mean serum IgE concentration of a group of 122 adult horses was 23,523ng/ml with a range of 425-82,610ng/ml. Total serum IgE of healthy horses was compared with that of horses with insect bite dermal hypersensitivity (IBDH) an allergic reaction to the bites of blood feeding insects of Culicoides or Simulium spp. IBDH does not occur in Iceland where Culicoides spp. are absent, but following importation into mainland Europe native Icelandic horses have an exceptionally high incidence of this condition. In the present study Icelandic horses with IBDH had significantly higher total IgE than healthy Icelandic horse controls (P<0.05). By contrast in horses of other breeds the difference in total serum IgE between those affected with IBDH and healthy controls was not statistically significant. Total serum IgE was also monitored in a cohort of Icelandic horses prior to import into Switzerland and for a period of 3 years thereafter. High levels of serum IgE were present in all horses at the start of the study but dropped in the first year after import. Thereafter the total serum IgE remained low in Icelandic horses that remained healthy but rose significantly (P<0.05) in those that developed IBDH. These results support the conclusion that IBDH is a type I hypersensitivity response to insect allergens but indicate that IBDH in Icelandic horses may have a different pathogenesis from the same condition in other breeds.

Short communication: Immunoglobulin variation in quarter-milked colostrum

Whereas whole first-milked colostrum IgG1 variation is documented, the IgG1 difference between the quarter mammary glands of dairy animals is unknown. First colostrum was quarter-collected from healthy udders of 8 multiparous dairy cows, all within 3h of parturition. Weight of colostrum produced by individual quarters was determined and a sample of each was frozen for subsequent analysis. Immunoglobulin G1 concentration (mg/mL) was measured by ELISA and total mass (g) was calculated. Standard addition method was used to overcome colostrum matrix effects and validate the standard ELISA measures. Analysis of the data showed that cow and quarter (cow) were significantly different in both concentration and total mass per quarter. Analysis of the mean IgG1 concentration of the front and rear quarters showed that this was not different, but the large variation in individual quarters confounds the analysis. This quarter difference finding indicates that each mammary gland develops a different capacity to accumulate precolostrum IgG1, whereas the circulating hormone concentrations that induce colostrogenesis reach the 4 glands similarly. This finding also shows that the variation in quarter colostrum production is a contributor to the vast variation in first milking colostrum IgG1 content. Finally, the data suggests other factors, such as locally acting autocrine or paracrine, epigenetic, or stochasticity, in gene regulation mechanisms may impinge on colostrogenesis capacity.