Risk of cardiovascular disease (CVD) mortality according to estimated glomerular filtration rate (eGFR) and age category.

<p>Shown are age-adjusted (A and B) and multivariable-adjusted (C and D) hazard ratios with 95% confidence intervals for CVD death with categorization according to eGFR in increments of 10 ml/min/1.73 m² for subjects of all ages, non-elderly subjects, or elderly men (A and C) and women (B and D). Each hazard ratio was calculated relative to the subpopulation with eGFR ≥60 ml/min/1.73 m². Adjusted factors for CVD death were age, body mass index, urinary protein concentration, blood pressure, use of anti-hypertensive drugs, serum triglyceride concentration, serum high-density lipoprotein concentration, serum total cholesterol concentration, use of lipid-lowering drugs, blood glucose concentration, treatment for diabetes, smoking, and alcohol consumption.</p

Distributions of cardiovascular disease (CVD) and non-CVD mortality rates according to estimated glomerular filtration rate (eGFR) in Japanese men and women.

<p>Distributions of CVD deaths and non-CVD deaths in men (A) and in women (B) were categorized according to eGFR in increments of 10 ml/min/1.73 m².</p

Risks of all-cause mortality and cardiovascular disease (CVD) mortality among subjects in CKD G3 category relative to those with eGFR ≥50 ml/min/1.73m².

<p>Risks of all-cause mortality and cardiovascular disease (CVD) mortality among subjects in CKD G3 category relative to those with eGFR ≥50 ml/min/1.73m².</p

Age-adjusted mean values for patient characteristics at baseline year according to eGFR category.

<p>Age-adjusted mean values for patient characteristics at baseline year according to eGFR category.</p

Differential glycan profiles of PNGase F-treated IgA1 of mIgA-MIDD.

<p>IgA1 purified from mIgA-MIDD serum was incubated with (left) or without (right) PNGase F. After digestion, the reaction mixture was labeled with Cy3-SE and subjected to the lectin microarray. The relative intensity of each lectin was normalized to the maximum fluorescence intensity. mIgA-MIDD, monoclonal immunoglobulin deposition disease associated with monoclonal IgA; PNGase F, peptide N-glycosidase F.</p

Lectin blot analysis of IgA1 purified from mIgA-MIDD serum under reducing and non-reducing conditions.

<p>IgA1 purified from mIgA-MIDD serum was pretreated in SDS buffer with or without 2-ME, separated by SDS-PAGE under non-reducing (lane 1) or reducing (lane 2) conditions, and then subjected to western blotting with an anti-IgA1 mAb (A), ConA (B), and WFA (C). Cross-reacting bands were detected using Konica immunostaining kit (Konica, Tokyo, Japan) for anti-IgA1 mAb and ConA and Western Lightning Chemiluminescence Plus (Perkin-Elmer, Boston, MA) for WFA. A Gal deficient IgA (lane 3), enzymatically deglycosylated with neuraminidase and galactosidase, was used as a positive control for WFA lectin. mIgA-MIDD, monoclonal immunoglobulin deposition disease associated with monoclonal IgA; 2-ME, 2-mercaptoethanol; ConA, jack bean lectin concanavalin A; WFA, Wisteria floribunda agglutinin.</p

IgA Nephropathy Caused by Unusual Polymerization of IgA1 with Aberrant N-Glycosylation in a Patient with Monoclonal Immunoglobulin Deposition Disease

<div><p>Immunoglobulin A nephropathy (IgAN) is a form of chronic glomerulonephritis characterized by the deposition of IgA immune complexes in the glomerular region. The cause of IgAN is unknown, but multiple mechanisms have been suggested. We previously reported a rare case of mesangioproliferative glomerulonephritis in a patient with monoclonal immunoglobulin deposition disease associated with monoclonal IgA1. In this study, we performed the detailed analyses of serum IgA1 from this patient in comparison with those from patients with mIgA plasma cell disorder without renal involvement and healthy volunteers. We found unusual polymerization of IgA1 with additional <i>N</i>-glycosylation distinctive in this patient, which was different from known etiologies. Glycan profiling of IgA1 by the lectin microarray revealed an intense signal for <i>Wisteria floribunda</i> agglutinin (WFA). This signal was reduced by disrupting the native conformation of IgA1, suggesting that the distinct glycan profile was reflecting the conformational alteration of IgA1, including the glycan conformation detected as additional <i>N</i>-glycans on both the heavy and light chains. This unusually polymerized state of IgA1 would cause an increase of the binding avidity for lectins. WFA specifically recognized highly polymerized and glycosylated IgA1. Our results of analysis in the rare case of a patient with monoclonal immunoglobulin deposition disease suggest that the formation of unusually polymerized IgA1 is caused by divergent mechanisms including multiple structural alterations of glycans, which contributes to IgA1 deposition and mesangium proliferation.</p></div

Differential glycan profiles of purified IgA1.

<p>IgA1 purified from sera of three HVs, two MPCD patients, and one mIgA-MIDD patient was subjected to lectin microarray. IgA1-binding signals on the lectin microarray were detected with a biotinylated anti-IgA1 mAb. The relative intensity of each lectin was normalized to the maximum fluorescence intensity. mIgA-MIDD, monoclonal immunoglobulin deposition disease associated with monoclonal IgA; MPCD, monoclonal IgA plasma cell disorder; HV, healthy volunteers.</p

Sandwich lectin ELISA of sequential deglycosylated IgA1 in mIgA-MIDD.

<p>IgA1 purified from mIgA-MIDD serum was digested with neuraminidase, and then β-galactosidase or β1,4-galactosidase. Digested and undigested samples were subjected to a sandwich lectin ELISA with HPA (A), VVA (B), PNA (C), and WFA (D) as described in the Methods. The relative intensity of each lectin was normalized to the IgA1 concentration. HPA, <i>Helix pomatia</i> agglutinin; VVA, <i>Vicia villosa</i> lectin; PNA, peanut agglutinin.</p

SDS-polyacrylamide gel electrophoresis analyses of purified IgA1.

<p>IgA1 purified from HV, MPCD, and mIgA-MIDD was boiled in SDS buffer with (A) or without (B) 2-ME and subjected to SDS-PAGE.</p