Do immune complexes formed with autoantibodies have a role in the maintenance of immune homeostasis through interaction with FC receptors.

Natural autoantibodies play an important regulatory role in the maintenance of immune homeostasis. They act as a first line of defense against environmental pathogens like toxins, bacteria and erythrocytes. In humans they are mainly produced by CD5+ B cells that are under the control of a regulatory T cell population. Fc-gamma receptors are involved in antigen recognition and signal transduction and tuning, and some of the members of the FcR family have structural similarity to MHC molecules; they may interact with multiple Ig ligands and with non-Ig ligands. We discuss the interactions between immune-complexes formed with natural autoantibodies and Fc-gamma receptors and suggest that such interactions may affect self-recognition in the thymus and regulate immune homeostasis.

Inhibition of Fc gamma receptors in the plasma of subjects with Down's syndrome.

Subjects with Down's syndrome have several immunological abnormalities. We examined the sera of 29 subjects with Down's syndrome for the presence of Fc gamma receptor blocking and for the presence of anti-ssDNA antibodies by EA rosette inhibition. Fifty-five percent of Down subjects had levels of inhibition above the upper limit of normality in comparison to 7% of normal controls. The finding that after polyethylene glycol precipitation of selected sera giving high levels of EA rosette inhibition there was a reduction or a disappearance of the EA rosette inhibition could indicate that the blocking factors detected behaved as immune complexes. Since almost all subjects with anti-ssDNA antibodies also had elevated values of EA rosette inhibition, a role for immune complexes eventually formed with autoantibodies in an Fc-mediated immunoregulatory system is suggested.

Immune complex-mediated inhibition of lymphocyte Fc-gamma receptors in the plasma of patients with type 1 (insulin-dependent) diabetes mellitus: association with anti-ssDNA antibodies.

Sera of 43 patients with type 1 (insulin-dependent) diabetes and from 42 normal subjects were examined for the presence of Fc-gamma receptor-blocking IgG immune complexes, detected by EA rosette inhibition, and for the presence of anti-ssDNA antibodies by ELISA. Forty-four percent of diabetic patients had levels of inhibition above the upper limit of normality in comparison to 7% of normal controls. Anti-ssDNA antibodies were found in the sera of 14 out of 43 diabetic patients. Ten out of 14 anti-ssDNA positive patients (71.5%) had inhibition levels above the upper limit of normality in comparison to 9 out of 29 (31%) of the anti-ssDNA negative population. The difference was statistically significant (P less than 0.005). Levels of EA rosette inhibition were found to be high in patients with duration of diabetes of less than 2 years and correlated with high prevalence of anti-ssDNA antibodies. The percentage of EA rosette inhibition was found not to correlate with the levels of C1q-binding immune complexes, suggesting that immune complexes detected by EA rosette inhibition may belong to a pool of noncomplement-fixing immune complexes. The possible role of immune complexes with autoantibodies anti-ssDNA in the mechanism triggering and perpetuating autoimmune phenomena in diabetes is discussed.

Purification of Parj I, a major allergen from Parietaria, judaica pollen.

A major allergen, the Parj I, was purified to homogeneity from Parietaria judaica pollen by means of ultrafiltration dialysis, preparative polyacrylamide gel chromatography and affinity chromatography through a column of Sepharose-monoclonal antibody specific for Parj I. The homogeneity of the Parj I was assessed by one single arc of immunoprecipitation both in cross immunoelectrophoresis (CIE) and crossed radioimmunoelectrophoresis, by one single band of radiostaining after a sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transfer to nitrocellulose and by one single peak after a size exclusion chromatography on high-performance liquid chromatography (HPLC). The homogeneity was further supported by crossed Laurell immunoelectrophoretic analysis, in that only one arc of precipitation was magnified in CIE after addition of the purified allergen. The purified Parj I allergen was capable of interacting in vitro with 70% of the human IgE specific for a crude P. judaica extract, as determined by radioallergosorbent test inhibition. The purified Parj I was capable of inducing positive reactions in vivo in skin prick tests, and of inducing release of histamine from blood containing basophils as determined by a histamine release assay. The amino acid analysis of the Parj I showed 118 amino acid residues per monomer analyzed and, among other residues, three methionine residues were detected. The molecular weight of the Parj I estimated by HPLC and amino acid composition was 26 kilodaltons.

A common epitope identified by a monoclonal antibody, MID 2, present on all leucocytes and associated with a group of high molecular weight glycopeptides.

A monoclonal antibody, MID 2, which reacts with an epitope common to all human leucocytes, was used to show that the leucocyte common antigen can be resolved into four glycoprotein components with molecular weights of 220 K, 200 K, 180 K and 160 K. The 200, 180 and 160 K peptides were all present to various extents in the T and B lymphoblastoid cell lines examined, but the 220 K component was only detected in the B-cell lines. The 220 K glycoprotein was also lacking in human thymocytes, but evidence of its expression in peripheral blood T lymphocytes was obtained, suggesting that it might be acquired as the cells differentiated. The four glycoproteins isolated from tonsil cells gave similar patterns on peptide mapping by the Cleveland enzymatic method or by cyanogen bromide cleavage, indicating extensive homology. It is conceivable that they differ from each other by the acquisition of similar repeating domain sequences of approximately 20 K. Alternatively, they may share a common peptide structure but differ in their electrophoretic behaviour in SDS gels owing to differences in carbohydrate; if this is the case, however, experiments with tunicamycin suggest that O-linked oligosaccharides must be involved.