T. Kokubo et al., Humoral immunity against the proline-rich peptide epitope of the IgA1 hinge region in IgA nephropathy, NEPH DIAL T, 15(1), 2000, pp. 28-33
Background. The human IgAl hinge region is a unique mucin-like O-linked pro
line-rich glycopeptide, and its core peptide was found to be exposed aberra
ntly by the underglycosylation in IgA nephropathy (IgAN). We describe here
the presence of humoral immunity against the IgAl hinge peptide epitope in
IgAN and evaluate the relationship between the underglycosylation of the Ig
Al hinge region and humoral immunity.
Method. The serum anti-IgAl hinge peptide antibody (anti-alpha 1HP ab) titr
e was measured and compared between the IgAN (n = 37) and control groups (n
= 34) by enzyme-linked immunosorbent assay (ELISA) using a synthetic pepti
de corresponding to the human IgAl hinge region, PVPSTPPTPSPSTPPTPSPS, as a
n antigen. Next, to evaluate the relationship between the underglycosylatio
n of the IgAl hinge region and the humoral immunity, the reactivity of the
serum IgG from the patients with IgAN against monoclonal IgAl which had bee
n digested enzymatically to remove the carbohydrates from the IgAl hinge re
gion was measured by ELISA.
Results. The anti-alpha 1HP ab titre was significantly higher in the IgAN g
roup than in the control group (OD value: IgG class, 0.564+/-0.344 vs 0.331
+/-0.154, P=0.0014, IgM class, 0.272+/-0.148 vs 0.141+/-0.072, P < 0.0001)
and it was positive in similar to 40% of the patients with IgAN. In additio
n, the reactivity of the serum IgG from the IgAN patients against the monoc
lonal IgAl was found to be increased as the carbohydrates were enzymaticall
y removed from the IgAl hinge region (when native = 100; asialo, 122+/-9.5;
agalacto, 167+/11.5, naked, 188+/-3.9).
Conclusion, These results suggested that the peptide epitope of the IgAl hi
nge region which was aberrantly exposed by underglycosylation could induce
the humoral immune response in IgAN.