An increase in the carbohydrate moiety of α2‐macroglobulin is associated with systemic lupus erythematosus (SLE)

Abstract

Using lectin blots in conjunction with peptide mapping, α2‐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; α2‐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 α2‐macroglobulin micropurified from serum samples of SLE patients is significantly higher than normal donors with a mean±SD of 188±410 μg/mg protein (SLE, n=23) versus 14.5±4 μg/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 α2‐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 α2‐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 α2‐macroglobulin and SLE. The concentration of mannose (38±60 μg/mg protein) in α2‐macroglobulin derived from SLE patients was significantly higher than normal donors (mannose, 4.8±1 μg/mg protein) however, the concentration of glucose in α2‐macroglobulin derived from SLE patients when compared to normal donors was not statistically significant, 18±20 μg/mg protein in SLE versus 2±0.5 μg/mg protein in normal donors due to high variation between samples. Also, the concentration of galactose in α2‐macroglobulin from SLE patients was significantly higher than normal donors (45.7±173 μg/mg protein versus 0.13±0.03 μg/mg protein). These results illustrate quantification of carbohydrate in selected glycoproteins such as α2‐macroglobulin may be a novel and alternative clinical marker for SLE.

Human plasma protein N-glycosylation

“…Changes in the glycosylation of alpha2M have been associated with autoimmune diseases and cancer. Site occupancy in particular has been linked with systemic lupus erythematosus, while a compositional change has been described in multiple sclerosis [ 73 , 74 ].…”

Glycosylation of Serum Proteins in Inflammatory Diseases

“…Using lectin blots in conjunction with peptide mapping, alpha 2-macroglobulin purified from systemic lupus erythematosus patients was shown to be abnormally glycosylated, suggesting the occurrence of complex glycosylation in this pathological condition [89]. When serum samples of normal donors, systemic lupus erythematosus patients, rheumatoid arthritis patients, a mixed connective tissue disease patient and a Sjogren's syndrome patient were analysed for carbohydrate content of alpha 2-macroglobulin it was not-ed that the concentration of total monosaccharides on alpha 2-macroglobulin purified from serum samples of systemic lupus erythematosus patients was significantly higher than in normal donors [89]. In the same study was also examined if there are any correlations between the levels of mannose and glucose on alpha 2-macroglobulin and systemic lupus erythematosus.…”

Potential of glycosylation research in graft versus host disease after allogeneic hematopoietic stem cell transplantation

“…Increased glycan moiety in α2-macroglobulin and the significantly higher content of galactose in the glycan of the same protein was reported [83]. Recent extensive study of three independent cohorts of SLE patients also observed significant changes in glycome composition, which correlate to the symptom severity [24].…”