title: Immune complex hyperlipidemia induced by an apolipoprotein-reactive immunoglobulin A paraprotein from a patient with multiple myeloma. Characterization of this immunoglobulin.
abstract: An antibodylike paraprotein has been isolated from a patient with multiple myeloma and autoimmune hyperlipoproteinemia. The paraprotein bound to apolipoprotein B (apo B)-containing lipoproteins that formed macromolecular aggregates, and globules thought to be aggregated complexes of lipoproteins and reactive immunoglobulins were observed circulating within the retinal blood vessels of this patient. This binding specificity permitted purification of the paraprotein from both the agglutinated immune complexes and from the plasma. The protein is an IgA, kappa-immunoglobulin which exists primarily in a polymeric state. Capillary immunoprecipitation demonstrated reactivity with very low density lipoproteins (VLDL) and low density proteins (LDL), but not with high density lipoproteins (HDL). Delipidated apo B and apo E, but not apo A or apo C, formed precipitates with this immunoglobulin. In using a radioimmunoassay format, the affinity of the immunoglobulin was greatest for VLDL and decreases sequentially for intermediate density lipoproteins and LDL. No binding occurred with a dispersion of LDL lipids or with HDL. Deglycosylation did not change the binding to LDL. The apolipoproteins B and E bound with similar affinity, but no binding occurred with apo A-I or apo A-II. Weak binding appeared to occur with apo C. This paraprotein immunoprecipitated apo B-containing lipoproteins from all classes of vertebrates tested. Displacement of the lipids of LDL by Triton X-100 resulted in the formation of an apo B-Triton complex which, however, did not bind to the immunoglobulin; apparently the binding site on apo B was lost. Upon enzymatic digestion with the IgA-specific protease from Streptococcus sanguis the immunoglobulin was cleaved into Fc and Fab fragments, and the binding of LDL occurred only with the latter, consistent with the behavior of an immunoglobulin. The immunoreactivity of this paraprotein with apo B and apo E raises the interesting possibility that it may be binding to a site on these apolipoproteins which is reactive with the apo B, E receptor of the plasma membrane, a site which is conserved throughout the vertebrate phylum.
authors.forename: L L
authors.initials: LL
authors.lastname: Kilgore
authors.forename: B W
authors.initials: BW
authors.lastname: Patterson
authors.forename: D M
authors.initials: DM
authors.lastname: Parenti
authors.forename: W R
authors.initials: WR
authors.lastname: Fisher
mesh_terms: D000368:Aged; D000936:Antigen-Antibody Complex; D001055:Apolipoproteins B / Q000276:immunology; D001057:Apolipoproteins E / Q000276:immunology; D006801:Humans; D006949:Hyperlipidemias / Q000276:immunology*; D007105:Immune Complex Diseases / Q000097:blood*; D007070:Immunoglobulin A / Q000276:immunology; D008077:Lipoproteins, LDL / Q000276:immunology; D008079:Lipoproteins, VLDL / Q000276:immunology; D008297:Male; D009101:Multiple Myeloma / Q000097:blood* / Q000276:immunology; D010265:Paraproteinemias / Q000097:blood; D010266:Paraproteins / Q000276:immunology
chemical_list: D000936:Antigen-Antibody Complex; D001055:Apolipoproteins B; D001057:Apolipoproteins E; D007070:Immunoglobulin A; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D010266:Paraproteins