Poly-IgA Complexes and Disease Severity in IgA Nephropathy

Xue Zhang, Jicheng Lv*, Pan Liu, Xinfang Xie, Manliu Wang, Dan Liu, Hong Zhang, Jing Jin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1652-1664
Number of pages13
JournalClinical Journal of the American Society of Nephrology
Volume16
Issue number11
DOIs
StatePublished - Nov 2021

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Nephrology
  • Transplantation
  • Epidemiology

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