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Abstract: PO1794

Role of the IgA Immune Complexes Bound to FcαRI/CD89 in IgA Nephropathy

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Zhang, Xue, Peking University First Hospital, Beijing, Beijing, China
  • Jin, Jing, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Lv, Jicheng, Peking University First Hospital, Beijing, Beijing, China
  • Wang, Manliu, Peking University First Hospital, Beijing, Beijing, China
  • Zhang, Hong, Peking University First Hospital, Beijing, Beijing, China
Background

Studies have demonstrated the pathogenic role of circulating polymers IgA immune complexes (poly-IgA ICs) in IgA nephropathy (IgAN). In this study we aim to evaluate the role of poly-IgA ICs specifically bound to FcαRI/CD89 in the kidney development of IgAN.

Methods

rCD89 protein was produced from a HEK293 cell expression system. A novel ELISA method that using rCD89 as the 'capturing' probe was established for detecting poly-IgA ICs. The plasma levels of poly-IgA ICs were measured in 181 IgAN patients and 35 patients with glomerular diseases of unrelated etiologies. Another 85 age-, gender-, and geographically-matched healthy individuals were enrolled as controls. rCD89-bound poly-IgA ICs were analyzed by mass spectrometry.

Results

rCD89-mounted plates specifically captured plasma poly-IgA. The levels of poly-IgA ICs in IgAN (26.67, 17.06 to 42.61 units/ml) were significantly higher than healthy controls (15.46, 10.73 to 20.04 units/ml; P<0.001) or disease controls (13.99, 10.35 to 24.22 units/ml; P<0.001). Patients with higher levels of poly-IgA ICs had lower eGFR, higher proteinuria and higher Oxford scores in E and T lesions. Accuracy parameters and concordant statistics showed good discrimination between IgAN and healthy controls for poly-IgA ICs levels (AUC, 0.777; 95% CI, 0.722–0.832; P<0.001), significantly better than IgA1 levels (AUC, 0.710; P=0.015) and galactose deficient-IgA1 levels (AUC, 0.702; P=0.048). A total of 268 proteins were identified in mass spectrometry analysis. The protein abundance of fibrinogen alpha chain, protein AMBP and C4B were higher in IgAN group.

Conclusion

Higher level of rCD89-bound poly-IgA ICs was a potential useful diagnostic biomarker in patients with IgAN which was also associated with the severity of the disease. The findings suggest that the role of CD89 in eliminating IgA ICs and it may be a new approach to improve the clinical progress of patients with IgAN.

The baseline clinical and pathological characteristics of IgA nephropathy patients
 TotalCD89-bound
poly-IgA ICs low-level
CD89-bound
poly-IgA ICs high-level
P value
Patients(n)
Male (%)
Age(ys)
MAP (mmHg)
Scr (μmol/L)
eGFR(ml/min)
Proteinuria (g/d)
Plasma IgA1 (mg/ml)
Plasma Gd-IgA1 (U/ml)
Oxford classification (%)
M1
E1
S1
T1/2
C1/2
181
82(45.3)
36.71±12.1
93.36±12.96
93.08(71.25, 137.6)
76.39±33.33
1.10(0.48, 2.4)
3.44±1.41
497.4±89

88(48.6)
61(33.7)
104(57.5)
69(38.1)
126(69.6)
85
42(49.4)
34.66±11.2
91.57±13.82
85.00(66.89, 126.6)
82.35±34.23
1.00(0.45, 1.92)
2.69±1.08
473.72±91.66

45(52.9)
22(25.9)
50(58.8)
22(25.9)
57(67.1)
96
40(41.7)
38.52±12.62
94.94±12
98.94(74.08, 144.83)
71.12±31.77
1.26(0.60, 2.5)
4.1±1.34
518.37±81.45

43(44.8)
39(40.6)
54(56.2)
47(49.1)
69(71.9)
-
0.296
0.032
0.080
0.093
0.023
0.131
<0.001
0.001

0.274
0.036
0.727
0.002
0.520

Plasma levels of CD89-bound poly-IgA ICs in groups