Pathway analysis of differentially expressed genes encoded outside the <i>HIVAN1</i> locus

<p>Pathway analysis of differentially expressed genes encoded outside the <i>HIVAN1</i> locus</p

Renal pathology scores in TgFVB and HIV-1 transgenic congenic and sub-congenic strains.

<p>Renal pathology scores in TgFVB and HIV-1 transgenic congenic and sub-congenic strains.</p

Albuminuria in TgFVB and the HIV-1 transgenic sub-congenic strains.

<p>Albuminuria is expressed as μg albumin/mg creatinine ratio. Statistically significant increase in albuminuria was observed in Sub-III and Sub-IV groups, but not in the Sub-II group when compared to TgFVB mice. (nonparametric P-value: *-p<0.05, **-p<0.01).</p

Map of the <i>HIVAN1</i> locus, congenic and sub-congenic regions.

<p>The rectangles depict the congenic and sub- congenic segments. The top line shows the position of the limiting markers in Mb (genome build 38p.3/mm10). The limiting markers with FVB genotypes are shown in blue, and those with CAST genotypes in red. The segments carrying CAST alleles are shown in grey. (Con = congenic strain)</p

Statistics summarized data; Discrimination between IgAN versus healthy and CKD controls for serum Gd-IgA1 and Gd-IgA1-specific IgG levels.

<p>* CKD non-immune-mediated renal disease includes diabetic nephropathy, nephrosclerosis, interstitial nephritis and Fabry's disease.</p><p>** CKD immune-mediated renal disease includes lupus nephritis, membranous nephropathy, minimal change disease, membranoproliferative glomerulonephritis, other types of non-IgAN glomerulonephritis.</p><p>***AIC: Akaike's Information Criterion.</p

Serum levels of Gd-IgA1-specific IgG in IgAN patients with high-Gd-IgA1 or normal-Gd-IgA1 in comparison to CKD and healthy controls.

<p>We divided IgAN patients into two subgroups: patients with serum levels of Gd-IgA1 ≥ the 90^th percentile for healthy controls (high-Gd-IgA1 group; n = 56) and patients with levels Gd-IgA1 < the 90^th percentile for healthy controls (normal-Gd-IgA1 group; n = 79). Although serum levels of Gd-IgA1-specific IgG were significantly higher in IgAN patients with high Gd-IgA1 levels (<i>vs.</i> CKD controls; *P<0.0001, <i>vs.</i> healthy controls; **P<0.0001), IgAN patients with normal Gd-IgA1 levels also had elevated Gd-IgA1-specific IgG (<i>vs.</i> CKD controls; *P<0.0001, <i>vs.</i> healthy controls; **P<0.0001).</p

Statistics summarized data; Discrimination between IgAN versus immune-mediated CKD and non-immune-mediated CKD controls for serum Gd-IgA1-specific IgG levels.

<p>PPV, Positive Predictive Value; NPV, Negative Predictive Value.</p

Correlation between biomarkers, histological findings and clinical findings.

<p>The strength of correlation between biomarkers, histological findings and clinical findings was measured by the Spearman's correlation coefficient. The serum level of Gd-IgA1-specific IgA correlated with the amount of mesangial IgA deposits (A). Histological prognostic stage (Clinical Guidelines for IgA Nephropathy in Japan, second version) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0098081#pone.0098081-Tomino1" target="_blank">[17]</a> correlated with the urinary protein/creatinine ratio (B), and percentage of glomeruli with a crescent (C).</p

Distribution of serum levels of (A) Gd-IgA1, (B) Gd-IgA1-specific IgG and (C) Gd-IgA1-specific IgA in patients with IgAN (n = 135), CKD controls (n = 79) and healthy controls (n = 106).

<p>Each biomarker was measured by capture ELISA. The serum levels of Gd-IgA, Gd-IgA1-specific IgG and Gd-IgA1-specific IgA were higher in IgAN patients compared with those of the CKD controls (*P<0.001) and healthy controls (**P<0.0001).</p

Characteristics of patients with IgAN and CKD controls.

<p>Values are mean ±SD.</p><p>eGFR, estimated glomerular filtration rate; P/C, protein/creatinine ratio; ND, not determined.</p><p>Hematuria: Assessed by assigning scores according to number of red blood cells per high-power field (RBC/HPF).</p><p>≤5 RBC/HPF  = 0, 6–10 RBC/HPF  = 1, 11–15 RBC/HPF  = 2, 16–20 RBC/HPF  = 3, 21–25 RBC/HPF  = 4, 26–30 RBC/HPF  = 5, >30 RBC/HPF  = 6.</p