Exposed peptide core of IgA1 hinge region in IgA nephropathy.
BACKGROUND
The human IgA1 hinge region is a very unique O-linked glycopeptide, and its sialylation and galactosylation recently were reported to be defective in the serum IgA1 derived from patients with IgA nephropathy (IgAN). This study was performed to examine the underglycosylation of the IgA1 hinge region and consequent exposure of the peptide core in IgAN.


METHODS
A polyclonal antibody against a synthetic human IgA1 hinge peptide, PVPSTPPTP SPSTPPTPSPS, (anti-sHP ab) was raised in rabbits and shown specifically to recognize the IgA1 which was treated with neuraminidase, beta-galactosidase and alpha-N-acetylgalactosaminidase. The reactivity of the anti-sHP ab against the purified serum IgA1 was compared among the following three groups: 39 patients with IgAN, 30 patients with other renal diseases (ORD) and 21 healthy controls (HC) using an enzyme-linked immunosorbent assay.


RESULTS
The reactivity was significantly higher in the IgAN group (mean +/- SD of OD 490 nm: 0.327 +/- 0.059) than in the ORD group (0.274 +/- 0.043, P=0.0002) and in the HC group (0.265 +/- 0.037, P<0.0001). No significant difference was observed between the latter two groups. The frequency of positive cases (> mean +/- 2SD of HC) was 46.2% (18/39) in the IgAN group, 6.7% (2/30) in the ORD group and 0% (0/21) in the HC group.


CONCLUSIONS
It was suggested that the peptide core of the IgA1 hinge region is exposed aberrantly by a defective N-acetylgalactosaminylation and plays a possible role in the pathogenesis of IgAN.
Kokubo
T
T
Department of Medicine, School of Medicine, Kitasato University, Sagamihara-city, Kanagawa, Japan.
Hiki
Y
Y
Iwase
H
H
Tanaka
A
A
Nishikido
J
J
Hotta
K
K
Kobayashi
Y
Y
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D000918:Antibody Specificity; D005260:Female; D005922:Glomerulonephritis, IGA / Q000097:blood / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood* / Q000737:chemistry / Q000145:classification; D007128:Immunoglobulin Fragments / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D011817:Rabbits
D000906:Antibodies; D007070:Immunoglobulin A; D007128:Immunoglobulin Fragments; D010446:Peptide Fragments