Progressive IgA Nephropathy Is Associated With Low Circulating Mannan-Binding Lectin-Associated Serine Protease-3 (MASP-3) and Increased Glomerular Factor H-Related Protein-5 (FHR5) Deposition

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  • Nicholas R Medjeral-Thomas, Centre for Complement and Inflammation Research, Imperial College London, London, UK.
  • ,
  • Anne Troldborg
  • Nicholas Constantinou, Centre for Complement and Inflammation Research, Imperial College London, London, UK.
  • ,
  • Hannah J Lomax-Browne, Centre for Complement and Inflammation Research, Imperial College London, London, UK.
  • ,
  • Annette G Hansen
  • Michelle Willicombe, Renal and Transplant Centre, Imperial College Healthcare NHS Trust, London, UK.
  • ,
  • Charles D Pusey, Renal and Vascular Inflammation Section, Imperial College London, London, UK.
  • ,
  • H Terence Cook, Centre for Complement and Inflammation Research, Imperial College London, London, UK.
  • ,
  • Steffen Thiel
  • Matthew C Pickering, Centre for Complement and Inflammation Research, Imperial College London, London, UK.

Introduction: IgA nephropathy (IgAN) is characterized by glomerular deposition of galactose-deficient IgA1 and complement proteins and leads to renal impairment. Complement deposition through the alternative and lectin activation pathways is associated with renal injury.

Methods: To elucidate the contribution of the lectin pathway to IgAN, we measured the 11 plasma lectin pathway components in a well-characterized cohort of patients with IgAN.

Results: M-ficolin, L-ficolin, mannan-binding lectin (MBL)-associated serine protease (MASP)-1 and MBL-associated protein (MAp) 19 were increased, whereas plasma MASP-3 levels were decreased in patients with IgAN compared with healthy controls. Progressive disease was associated with low plasma MASP-3 levels and increased glomerular staining for C3b/iC3b/C3c, C3d, C4d, C5b-9, and factor H-related protein 5 (FHR5). Glomerular FHR5 deposition positively correlated with glomerular C3b/iC3b/C3c, C3d, and C5b-9 deposition, but not with glomerular C4d. These observations, together with the finding that glomerular factor H (fH) deposition was reduced in progressive disease, are consistent with a role for fH deregulation by FHR5 in renal injury in IgAN.

Conclusion: Our data indicate that circulating MASP-3 levels could be used as a biomarker of disease severity in IgAN and that glomerular staining for FHR5 could both indicate alternative complement pathway activation and be a tissue marker of disease severity.

Original languageEnglish
JournalKidney International
Volume3
Issue2
Pages (from-to)426-438
Number of pages13
ISSN0085-2538
DOIs
Publication statusPublished - Mar 2018

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