Poly-IgA Complexes and Disease Severity in IgA Nephropathy.

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 serological detection of poly-IgA levels. Design, setting, participants, and measurements: A novel ELISA method using recombinant CD89 as 9capturing9 probe was established for detecting poly-IgA immune complex in the plasma. We applied semiquantitative measurements of these poly-IgA indices in patients recruited at Peking University First Hospital with IgA nephropathy or other kidney disease types, as compared to healthy controls. The longitudinal trend of the poly-IgA index, together with the association with pathological 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, IQR 17.1-42.6 units/ml) in IgA nephropathy were significantly higher than those in healthy (15.5, IQR 10.7- 20.0 units/ml; P<0.001), or non-IgA nephropathy disease controls (14.8, IQR 10.5-21.9 units/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 (AUC, 0.78; 95% CI, 0.72-0.83; P<0.001), significantly outperforming galactose deficient-IgA1 levels (AUC, 0.70; P=0.05). Corticosteroid and immunosuppressant treatments lowered poly-IgA indices. Following a recombinant CD89-directed workflow in conjunction with mass spectrometry, we also analyzed the molecular compositions of IgA immune complex in IgA nephropathy patients. Conclusions: Higher level of recombinant CD89-bound poly-IgA immune complex was associated with the severity of the disease, as well as treatment response to steroids and immunosuppressants.