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Abstract: TH-PO813

Collectin-11 Is a Recognition Molecule in Glomerular Activation of Lectin Pathway in IgA Nephropathy

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Guo, Weiyi, Renal Division, Peking University First Hospital, Beijing, China
  • Zhu, Li, Renal Division, Peking University First Hospital, Beijing, China
  • Shi, Sufang, Renal Division, Peking University First Hospital, Beijing, China
  • Liu, Lijun, Renal Division, Peking University First Hospital, Beijing, China
  • Lv, Jicheng, Renal Division, Peking University First Hospital, Beijing, China
  • Zhang, Hong, Renal Division, Peking University First Hospital, Beijing, China
Background

Glomerular activation of lectin pathway (LP) was reported in IgA nephropathy (IgAN), and further associated with disease severity and therapy. Besides mannose-binding lectin (MBL) and ficolin, which could recognize glycans of IgA1 and lead to LP complement activation in IgAN, collectin-11 (CL-11) is a newly identified recognition molecule in LP. Here we explored the involvement of CL-11 in complement activation of IgAN.

Methods

We enrolled 60 IgAN patients for Immunofluorescence staining of CL-11, MBL, ficolin, MASP2, MASP1/3, C4d, C3c and C5b-9 in renal biopsy specimens. Additionally, plasma samples from 10 patients with IgAN were collected for IgA1 purification. Using jacalin affinity chromatography, Sephrcryl S300 and glycosyl hydrolysis treatment, monomeric IgA1 (mIgA1), polymeric IgA1 (pIgA1), as well as sialic acid deficient IgA1 (SAd-IgA1) and sialic acid/galactose deficient IgA1 molecules (Gd/SAd-IgA1) were prepared and their binding with CL-11 were detected by ELISA.

Results

In our IgAN patients, 36.7% (22/60) had mesangial CL11 deposition. Among them, 14 also had MBL and ficolin deposition, 1 had MBL without ficolin, 4 had ficolin without MBL, while 3 without MBL or ficolin. All of the 22 IgAN patients with mesangial CL-11 deposition, presented with MASP (MASP2 or MASP1/3), C4d, C3 and MAC deposition, which co-localized with CL-11. In vitro, pIgA1 showed a Ca2+-independent binding with CL-11, and the binding was in a dose-dependent manner. Between concentrations of 0.625-2.5 ug/ml, pIgA1 showed significantly higher binding to CL-11 than mIgA1, while Gd/SAd-IgA1 had significantly higher binding to CL-11 than SAd-IgA1 and IgA1.

Conclusion

Our results suggested collectin-11 as a recognition molecule in LP in IgAN. Collectin-11 prone to bind with aberrant glycosylated polymeric IgA1, which might contribute to the glomerular complement activation of LP in IgAN.

Funding

  • Government Support - Non-U.S.