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Poly-IgA Complexes and Disease Severity in IgA Nephropathy
Clinical Journal of the American Society of Nephrology ( IF 8.5 ) Pub Date : 2021-11-01 , DOI: 10.2215/cjn.01300121
Xue Zhang 1, 2, 3, 4, 5 , Jicheng Lv 1, 2, 3, 4, 5 , Pan Liu 6 , Xinfang Xie 6 , Manliu Wang 1, 2, 3, 4, 5 , Dan Liu 7 , Hong Zhang 1, 2, 3, 4, 5 , Jing Jin 6
Affiliation  

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.

更新日期:2021-11-09
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