The aim of this work was to develop a simple assay to distinguish between patients with rheumatoid arthritis (RA) and patients with systemic lupus erythematosus (SLE) by measuring the serum sialylated IgG (SAIgG).
Methods
Using a newly established SNA-based ELISA method, we compared the sialylation of immunoglobulin G (IgG) from a healthy control group (n = 41), RA patients (n = 30), SLE patients (n = 45), patients with neuropsychiatric SLE (NPSLE) (n = 30) and patients with juvenile idiopathic arthritis (JIA) (n = 32).
Results
The average SAIgG level in healthy control individuals, RA patients, JIA patients, SLE patients and NPSLE patients was 0.64 ± 0.17, 0.82 ± 0.33, 0.69 ± 0.23, 0.12 ± 0.02 and 0.03 ± 0.01 mg/ml, respectively. The ratio of sialylated IgG to total IgG was significantly decreased in the SLE group (1.88 ± 0.32%) compared with the healthy population (4.64 ± 0.90%).
Conclusion
In summary, while the mean serum SAIgG level of RA and JIA patients was similar to that of the healthy population, there was a significant decrease in the serum SAIgG of both SLE groups tested, whereby the level of the NPSLE population group was the lowest.
YouingsAChangSCDwekRAScraggIG. Site specific glycosylation changes on human immunoglobulin G in pregnancy and rheumatoid arthritis. Biochem J1996; 314: 621–720.
2.
WormaldMWRuddPMHarveyDJChangSCScraggIGDwekRA. Variations in oligosaccharide protein interactions in immunoglobulin G determine the site specific glycosylation profiles and modulate the dynamic motion of the Fc oligosaccharides. Biochemistry1997; 36: 1370–1380.
3.
KäsermannFBoeremaDJRüegseggerM. Analysis and functional consequences of increased Fab-sialylation of intravenous immunoglobulin (IVIG) after lectin fractionation. PLoS One2012; 7: e37243.
4.
AxfordJSSumarNAlaviA. Changes in normal glycosylation mechanisms in autoimmunerheumatic disease. J Clin Invest1992; 89: 1021–1031.
5.
SchwabILuxANimmerjahnF. Reply to - IVIG pluripotency and the concept of Fc-sialylation: Challenges to the scientist. Nat Rev Immunol2014; 14: 349.
6.
OthySTopçuSSahaC. Sialylation may be dispensable for reciprocal modulation of helper T cells by intravenous immunoglobulin. Eur J Immunol2014; 44: 2059–2063.
7.
KanekoYNimmerjahnFRavetchJV. Anti-inflammatory activity of immunoglobulin G resulting from Fc sialylation. Science2006; 313: 670–673.
8.
AnthonyRMWermelingFRavetchJV. Novel roles for the IgG Fc glycan. Ann N Y Acad Sci2012; 1253: 170–180.
9.
AnthonyRMNimmerjahnFAshlineDJReinholdVNPaulsonJCRavetchJV. Recapitulation of IVIG anti-inflammatory activity with a recombinant IgG Fc. Science2008; 320: 373–376.
10.
LundJTakahashiNPoundJDGoodallMJefferisR. Multiple interactions of IgG with its core oligosaccharide can modulate recognition by complement and human Fc gamma receptor I and influence the synthesis of its oligosaccharide chains. J Immunol1996; 157: 4963–4969.
11.
MattuTSPleassRJWillisAC. The glycosylation and structure of human serum IgA1, Fab, and Fc regions and the role of N-glycosylation on Fcalpha receptor interactions. J Biol Chem1998; 273: 2260–2272.
12.
ParekhRBDwekRASuttonBJ. Association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum IgG. Nature1985; 316: 452–457.
13.
YoungASumarNBedmanK. Agalactosyl-IgG: an aid to differential diagnosis in early synovitis. Arthritis Rheum1991; 34: 1425–1429.
14.
WatsonMRuddPMBlandMDwekRAAxfordJS. Sugar printing rheumatic diseases: A potential method for disease differentiation using immunoglobulin G oligosaccharides. Arthritis Rheum1999; 42: 1682–1690.
15.
NiwaRNatsumeAUeharaA. IgG subclass-independent improvement of antibody-dependent cellular cytotoxicity by fucose removal from Asn297-linked oligosaccharides. J Immunol Methods2005; 306: 151–160.
16.
RuddPMElliottTCresswellPWilsonIADwekRA. Glycosylation and the immune system. Science2001; 291: 2370–2376.
17.
RitchieGEMoffattBESimRBMorganBPDwekRARuddPM. Glycosylation and the complement system. Chem Rev2002; 102: 305–320.
18.
MatsumiyaSYamaguchiYSaitoJ. Structural comparison of fucosylated and nonfucosylated Fc fragments of human immunoglobulin G1. J Mol Biol2007; 368: 767–779.
19.
TravingCSchauerR. Structure, function and metabolism of sialic acids. CMLS Cell Mol Life Sci1998; 54: 1330–1349.
20.
TomanaMSchrohenloherREKoopmanWJAlarcónGSPaulWA. Abnormal glycosylation of serum IgG from patients with chronic inflammatory diseases. Arthritis Rheum1988; 31: 333–338.
21.
DimitrovJDBayryJSiberilSKaveriSV. Sialylated therapeutic IgG: A sweet remedy for inflammatory diseases?. Nephrol Dial Transplant2007; 22: 1301–1304.
22.
FewouSNRamakrishnanHBussowHGieselmannVEckhardtM. Down-regulation of polysialic acid is required for efficient myelin formation. J Biol Chem2007; 282: 16700–16711.
23.
FranzCKRutishauserURafuseVF. Polysialylated neural cell adhesion molecule is necessary for selective targeting of regenerating motor neurons. J Neurosci2005; 25: 2081–2091.
24.
CangerAKRutishauserU. Alteration of neural tissue structure by expression of polysialic acid induced by viral delivery of PST polysialyltransferase. Glycobiology2004; 14: 83–93.
25.
SchauerR. Achievements and challenges of sialic acid research. Glycoconj J2000; 17: 485–499.
26.
YoshidaKTobetSACrandallJEJimenezTPSchwartingGA. Migration of luteinizing hormone-releasing hormone neurons in the developing rat is associated with a transient caudal projection of the vomeronasal nerve. J Neurosci1995; 15: 7769.
27.
BrusésJLRutishauserU. Roles, regulation, and mechanism of polysialic acid function during neural development. Biochimie2001; 83: 635–643.
