Abstract: TH-PO006

Dysregulation of the Alternative Complement Pathway in C3GN and IgAN

Session Information

Category: Glomerular

  • 1004 Clinical/Diagnostic Renal Pathology and Lab Medicine

Authors

  • Li, Yifu, Columbia University , New York, New York, United States
  • Marasa, Maddalena, Columbia University, New York, New York, United States
  • Steers, Nicholas J., Columbia University, New York, New York, United States
  • D'Agati, Vivette D., Columbia University College of Physicians and Surgeons, New York, New York, United States
  • Canetta, Pietro A., None, New York, New York, United States
  • Bomback, Andrew S., Columbia University, New York, New York, United States
  • Appel, Gerald B., Columbia University College of Physicians and Surgeons, New York, New York, United States
  • Kiryluk, Krzysztof, Columbia University, New York, New York, United States
  • Gharavi, Ali G., Columbia University, New York, New York, United States
Background


Dysregulation of the alternative pathway plays an important role in glomerular disease, including IgA nephropathy (IgAN) and C3 Glomerulopathy (C3GN). These disorders share some clinical manifestations, such as microscopic hematuria and episodes of synpharyngitic flares. Both are characterized by variable mesangial deposits of C3.

Methods


In this cross-sectional study, we collected plasma from 55 participants with IgAN, 105 diagnosed with C3GN, as well as from 62 unrelated healthy controls. All cases of IgAN and C3GN were diagnosed by biopsy. Major components of the alternative pathway, including C3, CFH and CFD levels, were measured by ELISA.

Results

Compared to controls, plasma CFD levels were higher in IgAN and C3GN groups. When compared to the IgAN group, the C3GN group has a significantly lower level of plasma C3 and CFH levels.

Conclusion


These data demonstrate dysregulation of the alternative complement pathway in both IgAN and C3GN. Lower C3 and CFH levels are characteristic of C3GN and differentiate it from IgAN. Analysis of larger cohorts during both active and inactive stages of the disease will better clarify shared and distinct complement profiles between these disorders.

ComplementCtrls (N=62)IgAN (N=55)C3GN (N=105)
C3 (ug/ml)1051.4±247.1908.6±142.3682.1±333.5**††
CFD (ng/ml)1120.3±446.22050.1±1341.0 **1592.6±1169.0 *
CFH (ug/ml)817.4±429.2938.8±485.1788.3±366.5††

* <0.05, ** <0.01 compared to ctrls; † <0.05, †† <0.01 compared to IgAN.