Histidine-rich glycoprotein prevents the formation of insoluble immune complexes by rheumatoid factor.
In previous studies we have shown that histidine-rich glycoprotein (HRG), a relatively abundant plasma protein, can bind to immunoglobulin G (IgG) and inhibit the insolubilization of IgG-containing immune complexes (IC). It was of interest, therefore, to determine whether HRG can inhibit the formation of insoluble IC (IIC) resulting from the interaction of rheumatoid factor (RF) with human IgG-containing IC. Light scattering techniques were used to examine the effect of HRG on the formation of IIC between RF and IC containing human IgG according to three different models. In all three models physiological concentrations of HRG could block the formation of IIC induced by RF. Optical biosensor studies of the RF-IgG interaction also revealed that HRG can mask the epitopes on IgG recognized by RF. Additional studies examined whether HRG can solubilize already formed IIC and demonstrated that HRG can, in fact, partially solubilized IIC. These data indicate that HRG can regulate the formation of IIC induced by RF at three levels: namely by inhibiting the initial recognition of IgG containing IC by RF, by inhibiting the subsequent insolubilization of IgG containing IC by RF and by solubilizing already formed IIC. Collectively, these findings suggest that HRG may be an important inhibitor of the formation of pathogenic IC in diseases such as systemic lupus erythematosus and rheumatoid arthritis.
Gorgani
N N
NN
Division of Immunology and Cell Biology, The John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia.
Altin
J G
JG
Parish
C R
CR
D000911:Antibodies, Monoclonal / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000187:drug effects / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D015374:Biosensing Techniques; D019921:Biotinylation; D006023:Glycoproteins / Q000494:pharmacology* / Q000627:therapeutic use; D006639:Histidine; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy; D011485:Protein Binding / Q000187:drug effects; D012217:Rheumatoid Factor / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D006023:Glycoproteins; D007074:Immunoglobulin G; D006639:Histidine; D012217:Rheumatoid Factor