Poly-IgA Complexes and Disease Severity in IgA Nephropathy. Issue 11 (November 2021)

• Record Type: Journal Article
• Authors: Zhang, Xue; Lv, Jicheng; Liu, Pan; Xie, Xinfang; Wang, Manliu; Liu, Dan; Zhang, Hong; Jin, Jing
• Is Part Of: Clinical journal of the American Society of Nephrology. Volume 16:Issue 11(2021)
• Page Start: 1652
• Page End: 1664
• Publication Date: 2021-11
• Subjects: IgA nephropathy -- glomerulonephritis -- immune complexes -- Fc receptors
• DOI: 10.2215/CJN.01300121
• Languages: English
• ISSNs: 1555-9041

Abstract

Visual Abstract: Abstract : Background and objectives: Poly-IgA immune complex formation and glomerular deposition play a key role in IgA nephropathy. Our study sought to develop a new methodology for one-step serologic detection of poly-IgA levels. Design, setting, participants, & measurements: A novel ELISA method using recombinant CD89 as a "capturing" probe was established for detecting poly-IgA immune complex in plasma. We applied semiquantitative measurements of these poly-IgA indices in patients recruited at Peking University First Hospital who had IgA nephropathy or other kidney disease types, as compared with healthy controls. The longitudinal trend of the poly-IgA index and the association with pathologic parameters and treatment responses were evaluated. Finally, we analyzed the molecular composition of poly-IgA complexes in patients by mass spectrometry. Results: Recombinant CD89–mounted ELISA plates specifically captured plasma poly-IgA. The levels of poly-IgA immune complex (26.7 [interquartile range (IQR) 17.1–42.6] U/ml) in IgA nephropathy were significantly higher than those in healthy controls (15.5 [IQR 10.7–20.0] U/ml; P <0.001) or in controls with non-IgA nephropathy disease (14.8 [IQR 10.5–21.9] U/ml; P <0.001). Higher levels of poly-IgA immune complex were associated with lower eGFR and worse kidney outcome. Accuracy parameters and concordant statistics showed good discrimination between IgA nephropathy and healthy controls based on poly-IgA index levels (area under the curve [AUC], 0.78; 95% confidence interval [95% CI], 0.72 to 0.83; P <0.001), significantly outperforming galactose-deficient IgA1 levels (AUC, 0.70; P =0.05). Corticosteroid and immunosuppressant treatments lowered poly-IgA indices. After a recombinant CD89–directed workflow in conjunction with mass spectrometry, we also analyzed the molecular composition of IgA immune complex in patients with IgA nephropathy. Conclusions: Higher level of recombinant CD89–bound poly-IgA immune complex was associated with the severity of the disease and with treatment response to steroids and immunosuppressants.