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Abstract: FR-PO851

C1q A08 Is a Half-Cryptic Epitope of Anti-C1qA08 Antibodies in Lupus Nephritis and Important for the Activation of Classical Complement Pathway

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Tan, Ying, Peking University First Hospital, Beijing, China
  • Zhao, Ming Hui, Peking University First Hospital, Beijing, China

Group or Team Name

  • Renal Division, Department of Medicine, Peking University First Hospital; Institute of Nephrology, Peking University
Background


Anti-C1q antibody is one of the most important autoantibodies in lupus nephritis, while its role in pathogenesis of lupus nephritis is not so clear.Our previous study found that C1q A08 antibody correlated better with lupus nephritis relapse than antibody against intact C1q molecule in a large Chinese cohort, and could predict reanl prognosis in lupus nephritis. This study aims to verify the role of A08 by anti-C1q A08 antibodies in lupus nephritis

Methods

Anti-C1q A08 antibodies from ten patients with lupus nephritis were purified from plasmapheresis samples. Four monoclonal antibodies against C1q A08 is screened from mouse hybridoma cells to study the conformational change of C1q in different situation by ELISA and Biolayer Interferometry (BLI) method. The biofunction of anti-C1q A08 antibodies in activation of classical complement pathway was investigated by C3 activation assay.

Results

All C1qA08 antibodies isolated from ten lupus nephritis patients could not bind C1q coating on microtiter plate and the anti-C1q autoantibodies were not able to bind to resin coupled with C1q A08 peptide, which indicates that different epitopes of C1q were recognized by C1q antibodies and C1q A08 antibodies. One of the four C1q A08 mAb(32-4) binds to six amino acids of the N-terminal, while another C1q A08 mAb(17-9) could bind to eight or ten amino acids of the C-terminal. The third and fourth C1q A08 mAb(1A12 and 4B11) could bind to the whole sequence of C1qA08(Figure 1). 32-4 mAb could bind to C1q coating on ELISA plate, while 17-9 mAb, 1A12 mAb and 4B11 mAb could not. However, different result was shown by BLI method. That is, 17-9 mAb, 1A12 mAb and 4B11 mAb could bind to C1q but 32-4 mAb could not. 1A12 mAb and 4B11 mAb were able to prevent the activation of classical complement pathway, while 32-4 and 17-9 mAb could not.

Conclusion


C1q A08 is one important but half-cryptic epitope of C1q, only part of the six amino acids is cryptic. A08 is important in activation of classical complement pathway and some anti- A08 antibodies were able to prevent this process.