Deglycosylation of Serum Vitamin D3-Binding Protein by α-N-Acetylgalactosaminidase Detected in the Plasma of Patients with Systemic Lupus Erythematosus

Abstract

A serum glycoprotein, Gc protein (vitamin D3-binding protein), can be converted by β-galactosidase of B cells and sialidase of T cells to a potent macrophage-activating factor (MAF), a protein withN-acetylgalactosamine as the remaining sugar moiety. Thus, Gc protein is the precursor for MAF. Treatment of Gc protein with immobilized β-galactosidase and sialidase generates a remarkably high titered macrophage-activating factor (GcMAF). When peripheral blood monocytes/macrophages (designated macrophages) of 33 systemic lupus erythematosus patients were incubated with GcMAF (100 pg/ml), the macrophages of all patients were activated as determined by superoxide generation. However, the precursor activity of patient plasma Gc protein was lost or reduced in these patients. Loss of the precursor activity was the result of deglycosylation of plasma Gc protein by α-N-acetylgalactosaminidase activity found in the patient plasma. Levels of plasma α-N-acetylgalactosaminidase activity in individual patients had an inverse correlation with the MAF precursor activity of their plasma Gc protein. Deglycosylated Gc protein cannot be converted to macrophage-activating factor. The resulting defect in macrophage activation may lead to an inability to clear pathogenic immune complexes. Thus, elevated plasma α-N-acetylgalactosaminidase activity resulting in the loss of MAF precursor activity and reduced macrophage activity may play a role in the pathogenesis of systemic lupus erythematosus.