Studies of the sialylation and microheterogeneity of human serum alpha 1-acid glycoprotein in health and disease.

The sialic acid content of alpha 1-acid glycoprotein (AGP) and its degree of microheterogeneity were investigated in AGP isolated from the pooled sera of patients with rheumatoid arthritis, or myocardial infarction or cancer (elevated AGP) or cancer (non-elevated AGP) and of healthy volunteers. Sialic acid was elevated in AGP preparations from the cancer groups and lowered in the preparation from the rheumatoid group. All preparations showed considerable charge heterogeneity by two dimensional polyacrylamide gel electrophoresis (2D-PAGE), but there was little evidence of molecular weight heterogeneity; the latter finding being also confirmed by peptide mapping studies. Each AGP preparation gave a different 2D-PAGE pattern; these differences were even more evident after partial desialylation of the samples when as many as fourteen different species could be identified. It is concluded from the sialic acid measurements and the 2D-PAGE study that the different preparations of AGP contain sialic acid in different carbohydrate structures. Using thin-layer electrofocusing (EF) and silver staining, characteristic AGP patterns could also be demonstrated after separating very small aliquots of unfractionated pooled and unpooled sera of the different groups. Therefore, EF measurements of AGP in serum may have a useful future role in clinical investigations.