Modulation of the assembly of immunoglobulin subunits by J chain.
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Alpha-Globulins↗
Biomedical subjects
S Hauptman
Publications and source records attributed to S Hauptman.
A monoclonal IgM protein with antibody-like activity for human albumin.
The serum of a patient (L'ec) with an IgM lambda monoclonal protein was noted to bind albumin on immunoelectrophoresis. Analytical ultracentrifugation of the L'ec serum demonstrated 23S and 12S peaks, but no 4S (albumin) boundary. Immunologically identical 20S and 9S IgM proteins were isolated from the serum and the addition in vitro of either the patient's albumin or albumin isolated from normal serum was shown to reconstitute the 23S and 12S boundaries. The binding of high molecular weight IgM to albumin was demonstated by Sephadex G200 chromatography with (125)I-labeled albumin and isolated IgM. Immunoelectrophoresis of the L'ec IgM developed with aggregated albumin (reverse immunoelectrophoresis) also demonstrated the binding of albumin to IgM. That all of the patient's IgM complexed with albumin was shown by affinity chromatography employing an aggregated albumin-immunoadsorbent column. Binding was shown to be of the noncovalent type by polyacrylamide gel electrophoresis in 8 M urea. With hot trypsin proteolysis, Fabmu and Fcmu5 fragments were isolated, and monomer albumin was shown to complex only with the Fabmu fragment by both analytical ultracentrifugation and molecular sieve chromatogaphy employing (125)I-labeled Fab fragments. 1 mol of Fabmu fragment bound 1 mol of monomer albumin. Polymers of human albumin, produced by heat aggregation, precipitated with the isolated L'ec protein on gel diffusion analysis and, when coated on sheep red blood cells, gave a hemagglutination titer greater than 1 million with the whole L'ec serum. 50 additional monoclonal IgM, 33 IgA, and 80 IgG sera failed to show precipitation or hemagglutination with aggregated albumin. Native monomer albumin inhibited precipitation only at high concentrations (> 50 mg/ml); dimer albumin or fragments of albumin produced by trypsin digestion inhibited at low concentrations (0.4 mg/ml). No reactivity occurred with the albumin of five other mammalian species, including bovine. The L'ec protein has the characteristics of an antibody against aggregated albumin, which also has reactivity with native (monomer) albumin. This system shares many similarities with the reaction of IgM human rheumatoid factors with IgG antigen.
Aged↗
Antibodies to human albumin in cirrhotic sera.
In a previous paper we described a monoclonal IgM protein with antibody-like activity towards aggregated and native albumin. The present study was initiated to determine whether sera, other than that from patients with macroglobulinemia, contained similar antibody-like activity. It was demonstrated that approximately 40% of the sera from patients with classical Laennec's cirrhosis contained antibodies which agglutinate sheep red blood cells coated with aggregated albumin. The hemagglutinating activity was present in the void volume on Sephadex G-200 chromatography and was shown to be an immunoglobulin by its removal on passage over an anti-L-chain immunoadsorbent column. The immunoglobulin was isolated from cirrhotic sera by chromatography on an albumin immunoadsorbent column. The acid eluate from the albumin affinity column contained only IgA. After labeling this IgA with (125)I and obtaining the Fabalpha fragment by proteolysis, it was shown that the labeled Fabalpha complexed noncovalently with aggregated albumin. Complex formation between albumin and the cirrhotic IgA and Fabalpha could also be demonstrated utilizing facilitation of hemagglutination of sheep red blood cells coated with aggregated albumin. Appropriate controls consisting of normal and myeloma IgA and myeloma Fabalpha fragments failed to show evidence of complex formation with albumin. We propose that the restriction of the antibody response to the IgA class may result from the formation of antibodies against albumin altered during metabolism in the gastrointestinal tract. A possible role for anti-albumin antibodies in normal albumin catabolism and in the pathogenesis of Laennec's cirhosis is discussed.
Alcoholism↗
Malingering with AIDS.
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Acquired Immunodeficiency Syndrome↗