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Background  Although serum under- O -glycosylated IgA1 in IgA nephropathy (IgAN) patients may deposit more preferentially in glomeruli than heavily- O -glycosylated IgA1, the relationship between the glomerular IgA deposition level and the  O -glycan profiles of serum IgA1 remains obscure.    Methods  Serum total under- O -glycosylated IgA1 levels were quantified in 32 IgAN patients by an enzyme-linked immunosorbent assay (ELISA) with  Helix aspersa  (HAA) lectin. Serum under- O -glycosylated polymeric IgA1 (pIgA1) was selectively measured by an original method using mouse Fcα/μ receptor (mFcα/μR) transfectant and flow cytometry (pIgA1 trap). The percentage area of IgA deposition in the whole glomeruli (Area-IgA) was quantified by image analysis on the immunofluorescence of biopsy specimens. Correlations were assessed between the Area-IgA and data from HAA-ELISA or pIgA1 trap. The relationships between clinical parameters and data from HAA-ELISA or pIgA1 trap were analyzed by data mining approach.    Results  While the under- O -glycosylated IgA1 levels in IgAN patients were significantly higher than those in healthy controls when measured (p < 0.05), there was no significant difference in under- O -glycosylated pIgA1. There was neither a correlation observed between the data from HAA-ELISA and pIgA1 trap (r 2  = 0.09) in the IgAN patients (r 2  = 0.005) nor was there a linear correlation between Area-IgA and data from HAA-ELISA or the pIgA1 trap (r 2  = 0.005, 0.03, respectively). Contour plots of clinical parameters versus data from HAA-ELISA and the pIgA1 trap revealed that patients with a high score in each clinical parameter concentrated in specific areas, showing that patients with specific  O -glycan profiles of IgA1 have similar clinical parameters. A decision tree analysis suggested that dominant immune complexes in glomeruli were consisted of: 1) IgA1-IgG and complements, 2) pIgA1 and complements, and 3) monomeric IgA1-IgA or aggregated monomeric IgA1.    Conclusions  Serum under- O -glycosylated IgA1 levels are not correlated with glomerular IgA deposition based upon heterogeneity in the composition of glomerular immune complexes in IgAN patients.

bmc nephrology

Serum under-O-glycosylated IgA1 level is not correlated with glomerular IgA deposition based upon heterogeneity in the composition of immune complexes in IgA nephropathy