ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: PO1743

Glomerular Complement Proteins in Thrombotic Microangiopathy

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Palma, Lilian MP, Universidade Estadual de Campinas, Campinas, SP, Brazil
  • Sridharan, Meera, Mayo Clinic, Rochester, Minnesota, United States
  • Johnson, Kenneth L., Mayo Clinic, Rochester, Minnesota, United States
  • Madden, Benjamin J., Mayo Clinic, Rochester, Minnesota, United States
  • Charlesworth, Cristine, Mayo Clinic, Rochester, Minnesota, United States
  • Sethi, Sanjeev, Mayo Clinic, Rochester, Minnesota, United States
Background

Thrombotic Microangiopathy (TMA) is a clinicopathological entity resulting from complement abnormalities (atypical hemolytic uremic syndrome, aHUS) and a number of secondary causes including malignant hypertension, autoimmune diseases and drugs. Distinguishing aHUS from secondary TMA is a challenge. A comprehensive evaluation of complement burden in TMA has not been done.

Methods

Glomeruli were laser microdissected and mass spectrometry (MS) was performed. The glomerular complement protein profile was analyzed in aHUS (n=12) and secondary TMA (n=12). The spectral counts obtained from MS are semiquantitative with regards to abundance of the protein.

Results

C3 was the most the abundant complement protein in all cases (Figure). The remaining complement proteins were grouped into classical (C1/C4A/C4B), terminal pathway (C5/6/7/8A/8B/9), and complement regulatory proteins (CRP=CFH/CFHR1-2-3-5/CFB/CFD). MS studies show accumulation of C3, and complement proteins of classical and terminal pathways in all cases. Overall, there was greater accumulation of complement proteins in secondary TMA compared to aHUS (248.3 vs. 192.5). Importantly, even though C3 was higher in aHUS, both classical pathway and terminal pathway protein accumulation were higher in secondary TMA compared to aHUS. Among the secondary TMA, drug-induced TMA showed the highest accumulation of complement proteins compared to autoimmune and hypertension-induced TMA (306.9 vs. 217 vs. 219.9, respectively). Finally, CRP were present in all TMA, of which CFH was the most abundant protein.

Conclusion

Complement proteins of all pathways were identified in TMA. C3 followed by C4A/C4B and C9 were most abundant proteins. Higher counts of C3 in aHUS versus higher counts of C4A/C4B in secondary TMA, suggests a greater role of alternative pathway in aHUS and a greater role of classical pathway in secondary TMA.

MS: Total spectral counts in TMA.