O-glycans on IgAl hinge region in IgA nepbregathy.
| Project/Area Number |
05807099
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Kidney internal medicine
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| Research Institution | Kitasato University |
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Principal Investigator |
HIKI Yoshiyuki Kitasato Univ., School of Nursing, Lecturer, 看護学部, 講師 (20156566)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1994: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1993: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | IgA nephropathy / IgAl / Jacalin / O-glycan / sialic acid / Gal-GalNAc / melibiose / galactose / IgA1 / ムチン型糖鎖 / O型糖鎖 |
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| Research Abstract |
1. Serum IgA possessing an affinity to IgA was significantly increased in the patients with IgA nephropathy (IgA-N) compared with healthy controls and the patients with other primary glomerulonephritis (OPGN) .
2. The frequencies of the patients with serum IgA1 having a high affinity for jacalin were significantly greater in IgA-N (19/58,32.8%) compared with the healthy controls and other PGN.These results suggested that the increased reactivity of O-glycan (s) in the IgA1 hinge region to jacalin is due to an unusual glycosylation of serum IgAl in IgA-N.
3. O-linked oligosaccharides were specifically released from the IgA1 hinge region by gas-phase hydrazinolysis and the glycoform of O-glycans were analyzed. It was found that the glycoforms of the carbohydrate in IgA-N were significantly different from that of the negative control group. In other words, there was a significant shift from mono-sialylated Galbeta1-3GalNAc to asialo-Galbeta1-3GalNAc in both groups. These results suggested the presence of an unusual glycosylation in O-glycan (s) on the IgA1 hinge region in some of IgA-N.
4. The binding of IgA1 to both of the stimulated monocyte/macrophage cell lines (THP-1&U937) was increased in IgA-N compared to normal and other GN.The binding of IgA1 to THP-1 was partially but definitely inhibited by adding melibiose and galactose but not by glucose, lactose and mannose. These results suggested that THP-1 had a receptor that recognized the O-glycan on the IgA1 hinge region.
5. To investigate the IgA-IgA interaction, purified IgA1 was applied on asialo-IgA1 column and the elution pattern was observed. There was a definite retardation of the peak. And the retardation was decreased by galactose and disappeared by melibiose. Therefore it was suggested that there was a low affinity IgA1-IgA1 interaction mediated by asialo-GalGalNAc, resulting the formation of macromolecule IgA capable of depositing in glomeruli.
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Report
(3 results)
Research Products
(23 results)
