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-macroglobulin micropurified from systemic lupus erythematosus (SLE) patients was shown to become abnormally glycosylated suggesting the occurrence 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 female), 23 SLE patients, 6 rheumatoid arthritis patients, 1 mixed connective tissue disease patient, and 1 Sjogren's syndrome patient; for carbohydrate analysis. It was noted that the concentration of total monosaccharides in alpha 2-macroglobulin micropurified from serum samples of SLE patients is significantly higher than normal donors with a mean +/- SD of 188 +/- 410 micrograms/mg protein (SLE, n = 23) versus 14.5 +/- 4 micrograms/mg protein (normal, n = 6) even though there was a high variation in the level of monosaccharides among the SLE patients. An increase in oligosaccharides in alpha 2-macroglobulin from SLE patients compared to normal subjects was confirmed by concanavalin A (Con A) blots using peptide fragments derived from the micropurified protein. Since the interaction of peptide fragments derived from alpha 2-macroglobulin with Con A requires the presence of mannose and/or glucose residues, we have also examined if there are any correlations between the levels of mannose and glucose in alpha 2-macroglobulin and SLE. The concentration of mannose (38 +/- 60 micrograms/mg protein) in alpha 2-macroglobulin derived from SLE patients was significantly higher than normal donors (mannose, 4.8 +/- 1 micrograms/mg protein) however, the concentration of glucose in alpha 2-macroglobulin derived from SLE patients when compared to normal donors was not statistically significant, 18 +/- 20 micrograms/mg protein in SLE versus 2 +/- 0.5 micrograms/mg protein in normal donors due to high variation between samples. Also, the concentration of galactose in alpha 2-macroglobulin from SLE patients was significantly higher than normal donors (45.7 +/- 173 micrograms/mg protein versus 0.13 +/- 0.03 microgram/mg protein). These results illustrate quantification of carbohydrate in selected glycoproteins such as alpha 2-macroglobulin may be a novel and alternative clinical marker for SLE.
Panzironi
C
C
The Population Council, New York, NY 10021, USA.
Silvestrini
B
B
Mo
M Y
MY
Lahita
R
R
Mruk
D
D
Cheng
C Y
CY
D000906:Antibodies / Q000097:blood; D002241:Carbohydrates / Q000032:analysis / Q000097:blood*; D004247:DNA / Q000276:immunology; D005260:Female; D005688:Galactosamine / Q000032:analysis; D005690:Galactose / Q000032:analysis; D005944:Glucosamine / Q000032:analysis; D005947:Glucose / Q000032:analysis; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood*; D008297:Male; D008358:Mannose / Q000032:analysis; D000511:alpha-Macroglobulins / Q000032:analysis / Q000378:metabolism*
D000906:Antibodies; D002241:Carbohydrates; D000511:alpha-Macroglobulins; D005688:Galactosamine; D004247:DNA; D005947:Glucose; D005944:Glucosamine; D008358:Mannose; D005690:Galactose