POS-388 Role Of Serum Galactose Deficient IgA1 As A Noninvasive Biomarker For Diagnosis Of IgA Nephropathy And Its Role In Assessing The Genetic Susceptibility Of Disease

Abstract

IgA nephropathy(IgAN) is the most common primary glomerular disease with a high risk of progression. Over the years, research has focused on establishing a biomarker for this disease. Galactose deficient IgA1 (Gd-IgA1) is a crucial molecule in the pathogenesis of IgAN and serum levels have found high in previous studies. So this molecule may have potential to be used as a biomarker for IgAN . Aberrant galactosylation of IgA1 could be inherited and family members are predisposposed for the diseaseAims : To determine whether serum Gd-IgA1 levels can be used as a noninvasive biomarker for diagnosis of IgAN. To assess the serum Gd-IgA1 levels in the first degree relatives of patients with IgAN to predict possible heritability of aberrant galactosylation of IgA1.To correlate serum Gd-IgA1 levels with disease severity by clinical and histological parameters We measured serum Gd-IgA1 levels using a non- lectin based enzyme linked immunoassay (ELISA) in 40 biopsy proved IgAN patients and 38 healthy controls. In control group (n=38) we included 18 healthy first degree relatives of IgAN patients.Quantification of Gd-IgA1from patients sample were carried out by using optical density (OD) reading obtained from each sample and comparing with each graph.Receiver operating characteristic (ROC) curve was drawn for serum Gd-IgA1 levels and optimum cut off was determined. Area under the curve (AUC) and 95% confidence interval (CI) for AUC was estimated. Diagnostic validity of serum Gd-IgA1 levels test was determined by sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Efficiency, likelihood ratio for a positive result (LR+) and likelihood ratio for a negative result (LR-) were also calculated Mean serum Gd-IgA1 levels were higher in IgAN patients (n=40) 1631.9.±1997.5ng/ml compared with healthy controls (n=38) 429.81.± 571.28 ng/ml.Median (min, max) values were 629 (104.48, 7959.1) and 285.78(18.44, 3152.9) respectively (p<0.0001).Considering a cut-off value of serum Gd-IgA1 ≥ 454.8 ng/ml, the sensitivity for diagnosing IgAN compared to healthy controls without family history (n=20) was 75.3% and specificity 85 % with a positive predictive value of 90.9 % and negative predictive value of 63 % .The area under the curve (AUC) was 0.85 ( 0.749- 0.951 ), p<0.0001 . Efficiency of test was 78.1% , likelihood ratio for a positive result ( LR+) was 5 and likelihood ratio for a negative result ( LR-) was 0.29. When IgAN patients were compared with total controls(n=38) for the same cut off, sensitivity was same with specificity of 71.7 %, positive predictive value of .73.2 % and negative predictive value of 73%. Serum Gd-IgA1 levels in healthy controls with family history were significantly high compared to those without family history (384.12ng/mlvs.202 .81ng/ml, p=0.022) The serum Gd-IgA1 level did not correlate with clinical or histological disease severity parameters Serum Gd-IgA1 level can be used as a potential biomarker for diagnosis of IgAN . High levels of Gd-IgA1 levels in the first degree relatives of patients with IgAN suggests possible heritability of aberrant galactosylation of IgA1 and may predict risk of disease manifestation after a second hit in future. Serum Gd-IgA1 level can’t be used to assess disease severity