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Significance of serum galactose deficient IgA1 as a potential biomarker for IgA nephropathy: A case control study.

ABSTRACT: BACKGROUND:IgA nephropathy(IgAN) is a common glomerular disease with a higher risk of progression to end stage renal disease (ESRD) in certain ethnic populations. Since galactose deficient IgA1(Gd-IgA1) is a critical molecule in its pathogenesis, it has generated interest as a biomarker for this disease. METHODS:We measured serum Gd-IgA1 levels using a non- lectin based enzyme linked immunoassay(ELISA) in 136 immunosuppression naïve patients with primary IgAN and 110 controls(60-non IgA glomerular diseases, 50-healthy volunteers). RESULTS:Median serum Gd-IgA1 levels were significantly higher in IgAN patients [13135.6(2723.3,59603.8)ng/ml] compared to those with non IgA glomerular disease [4954.8(892.9,18256.2) ng/ml] and healthy controls [6299.5(1993.2,19256) ng/ml] and this was observed even after log transformation and adjustment for age and gender(p<0.0001). Considering a cut-off value of serum Gd-IGA1?7982.1ng/ml, the sensitivity for diagnosing IgAN compared to healthy controls was 74.3% and specificity was 72.0% with a positive predictive value of 87.8% and negative predictive value of 50.7%. The serum Gd-IgA1 level did not co-relate with baseline estimated glomerular filtration rate, urine protein creatinine ratio and the M, E, S, T and C scores on renal biopsy. The renal survival (absence of >30% decrease in eGFR, ESRD or death) was lower in patients with higher serum Gd-IgA1 levels(?7982ng/ml) than those who had lower levels but it was not statistically significant(p = 0.486). CONCLUSION:Serum Gd-IgA1 level is higher in IgAN patients compared to non-IgA glomerular diseases and healthy controls and has a good positive predictive value for diagnosis. However, it does not correlate with clinical and histological characteristics of disease severity and does not predict disease progression.

SUBMITTER: Bagchi S

PROVIDER: S-EPMC6436754 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Significance of serum galactose deficient IgA1 as a potential biomarker for IgA nephropathy: A case control study.

Bagchi Soumita S Lingaiah Raghavendra R Mani Kalaivani K Barwad Adarsh A Singh Geetika G Balooni Veena V Bhowmik Dipankar D Agarwal Sanjay Kumar SK

PloS one 20190327 3

<h4>Background</h4>IgA nephropathy(IgAN) is a common glomerular disease with a higher risk of progression to end stage renal disease (ESRD) in certain ethnic populations. Since galactose deficient IgA1(Gd-IgA1) is a critical molecule in its pathogenesis, it has generated interest as a biomarker for this disease.<h4>Methods</h4>We measured serum Gd-IgA1 levels using a non- lectin based enzyme linked immunoassay(ELISA) in 136 immunosuppression naïve patients with primary IgAN and 110 controls(60-n ...[more]

PMID: 30917188

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Project description:IntroductionGalactose-deficient IgA1 (Gd-IgA1) is a critical pathogenic factor for IgA nephropathy (IgAN), but its value as a disease-specific biomarker remains controversial. We aimed to clarify the clinical significance of Gd-IgA1 in patients with IgAN.MethodsWe retrospectively reviewed 111 patients who were diagnosed with IgAN based on the findings of renal biopsies (RB) at Showa University Hospital since 2007. Serum Gd-IgA1 (s-Gd-IgA1) at the time of RB was compared among 111 IgAN patients, 18 Henoch-Schönlein purpura nephritis (HSPN) patients, 29 lupus nephritis (LN) patients, 28 ANCA-associated vasculitis (AAV) patients, and 13 minimal change disease (MCD) patients using ELISA with an anti-human Gd-IgA1-specific monoclonal antibody (KM55). We also immunohistochemically stained paraffin-embedded sections for mesangial Gd-IgA1 (m-Gd-IgA1) deposition using KM55.ResultsAlthough levels of s-Gd-IgA1 were comparable among IgAN and HSPN, s-Gd-IgA1 levels were significantly elevated in patients with IgAN compared with LN, AAV and MCD (IgAN vs. HSPN, LN, AAV, and MCD: 16.2 ± 9.1 vs. 14.2 ± 10.8, p = 0.263; 12.7 ± 9.4, p = 0.008; 13.1 ± 7.3, p = 0.059; and 8.2 ± 4.8 μg/mL, p<0.001, respectively). Mesangial-Gd-IgA1 deposition was specifically detected in IgAN or HSPN. The increase in s-Gd-IgA1 significantly correlated with m-Gd-IgA1 positivity in patients with IgAN, and s-Gd-IgA1 elevation and m-Gd-IgA1 deposition were evident in patients with histopathologically advanced IgAN. Moreover, s-Gd-IgA1 levels were significantly higher in IgAN patients with glomerular sclerosis and tubulo-interstitial lesions. Mesangial-Gd-IgA1 intensity negatively correlated with eGFR in IgAN. Multivariate analysis selected s-Gd-IgA1 elevation as a significant risk factor for a 30%-reduction in eGFR in IgAN (HR, 1.37; 95% CI, 1.02-1.89; p = 0.038).ConclusionsAlthough IgAN and HSPN remain difficult to differentiate, s-Gd-IgA1 elevation and m-Gd-IgA1 deposition are reliable diagnostic factors that reflect IgAN severity. Serum-Gd-IgA1 could serve as a predictor of renal outcomes in IgAN. Thus, Gd-IgA1 could be significant biomarker for patients with IgAN.

Dataset Information

Significance of serum galactose deficient IgA1 as a potential biomarker for IgA nephropathy: A case control study.

Publications

Significance of serum galactose deficient IgA1 as a potential biomarker for IgA nephropathy: A case control study.

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