Fernando A. Salinas

Immune complexes and human neoplasia.

SummaryWe have investigated the membrane-binding properties of fetal liver cells (FLC) and developed an assay to quantitate circulating immune complexes (CIC) based on complement (C) receptor binding on FLC. Both binding and blocking studies identified FLC membrane receptors for IgG-Fc, C, and antifetal antibodies (FL-Ab), but not IgG F(ab)′2. Fc binding of IgG or aggregated human IgG (AHG) was relatively weak, with an association constant of 1.5×107 l/mol. In contrast, there was a six- to seven-fold increase in binding of AHG by C receptors, with an association constant of 108 l/mol. A simple and sensitive procedure for detecting CIC in the sera of patients with various disease states has been developed by the use of C receptors on FLC. Reference to an AHG standard curve permits quantitation of CIC in micrograms of AHG equivalent per milliliter of serum. Clinical evaluation in patients with active collagen vascular disease and in cancer patients confirmed the reliability, specificity of binding, and sensitivity of the FLC method. Although there was overall agreement with the Raji cell method for CIC detection, FLC-RIA quantiation of CIC was found to be more sensitive than the Raji cell assay. Other discrepancies could be explained by differing sensitivity to CIC size.

Clinical Relevance of Immune Complexes, Associated Antigen, and Antibody in Cancer

During the past 15 years there has been an increased interest in tumor-associated antigens (TAA) and the potential clinical role their immunologically oriented markers may play in the management of human cancer. One such immunological test for human tumor-associated markers, the identification of circulating immune complexes (CIC), is the subject of this volume.

Elevated IgG immune complexes in children with atopic eczema

The levels of serum IgG complement-fixing immune complexes were studied in 20 children with atopic eczema and in 10 children with allergic rhinitis as control subjects with the use of a Raji cell assay. Immune-complex levels were strikingly elevated in those with eczema, 50 +/- 10 SE micrograms/ml, compared to control subjects 11 +/- 9 micrograms/ml (p less than 0.0047), the latter falling within the range for nonallergic subjects. Levels tended to be higher in those subjects with more severe eczema, but there was no statistically significant correlation, nor were levels correlated with serum IgE. Sucrose-density gradient analysis demonstrated the immune complexes to be present in two peaks, 8 to 10S and 21S or higher. High-molecular-weight IgG immune complexes that are complement-fixing may promote the characteristic pruritus of eczema by formation of anaphylactic complement fragments and the release of inflammatory substances from cutaneous mast cells, as well as contributing to the impaired cell-mediated immunity associated with the disease.

Advances Towards Clinical Relevance of Breast Carcinoma Associated Antigens

Use of monoclonal antibodies Mc 3 and Mc 8, and the respective human mammary epithelial antigens (HME Ags), has enabled the isolation, characterization and identification of free and bound antigenic moieties extracted from breast carcinoma (BC) patients’ sera immune reactants. As a result we have been able to compare and identify reactive similarities encountered with either source of antigens. Both isolated antigens (BCAA), and Mc 3 and Mc 8 monoclonals have been reacted with BC patients’ sera grouped according to tumor burden by use of an in vitro model of tumor burden change. Results of this interaction have provided insight into relative concentration of free antigen:antibodies at differing tumor burden load. The effects of circulating immune complexes (CIC) and antibodies on free circulating BCAA levels, and their relationship to tumor burden have resulted in a better understanding of clearance, pathogenetic deposition and ultimate fate of CIC. An evaluation of free circulating BCAA in BC patients’ sera demonstrated that despite BCAA not correlating linearly with tumor burden, BCAA represent a useful marker to clinically monitor tumor burden changes.