AN INCREASE IN THE CARBOHYDRATE MOIETY OF ALPHA(2)-MACROGLOBULIN IS ASSOCIATED WITH SYSTEMIC LUPUS-ERYTHEMATOSUS (SLE)

Using lectin blots in conjunction with peptide mapping, alpha(2)-macro globulin micropurified from systemic lupus erythematosus (SLE) patient s was shown to become abnormally glycosylated suggesting the occurrenc e of complex glycosylation in this pathological condition. To confirm there is indeed a quantitative increase in specific monosaccharides in this protein; alpha(2)-macroglobulin was micropurified from a battery of 37 serum samples which included 6 normal donors (3 male and 3 fema le), 23 SLE patients, 6 rheumatoid arthritis patients, 1 mixed connect ive tissue disease patient, and 1 Sjogren's syndrome patient; for carb ohydrate analysis. It was noted that the concentration of total monosa ccharides in alpha(2)-macroglobulin micropurified from serum samples o f SLE patients is significantly higher than normal donors with a mean/-SD of 188+/-410 mu g/mg protein (SLE, n=23) versus 14.5+/-4 mu g/mg protein (normal, n=6) even though there was a high variation in the le vel of monosaccharides among the SLE patients. An increase in oligosac charides in alpha(2)-macroglobulin from SLE patients compared to norma l subjects was confirmed by concanavalin A (Con A) blots using peptide fragments derived from the micropurified protein. Since the interacti on of peptide fragments derived from alpha(2)-macroglobulin with Con A requires the presence of mannose and/or glucose residues, we have als o examined if there are any correlations between the levels of mannose and glucose in alpha(2)-macroglobulin and SLE. The concentration of m annose (38+/-60 mu g/mg protein) in alpha(2)-macroglobulin derived fro m SLE patients was significantly higher than normal donors (mannose, 4 .8+/-1 mu g/mg protein) however, the concentration of glucose in alpha (2)-macroglobulin derived from SLE patients when compared to normal do nors was not statistically significant, 18+/-20 mu g/mg protein in SLE versus 2+/-0.5 mu g/mg protein in normal donors due to high variation between samples. Also, the concentration of galactose in alpha(2)-mac roglobulin from SLE patients was significantly higher than normal dono rs (45.7+/-173 mu g/mg protein versus 0.13+/-0.03 mu g/mg protein). Th ese results illustrate quantification of carbohydrate in selected glyc oproteins such as alpha(2)-macroglobulin may be a novel and alternativ e clinical marker for SLE.