Kidney Week

Abstract: SA-PO618

A Modified Peptide Derived from Goodpasture Autoantigen Arrested and Attenuated Kidney Injuries in Experimental Anti-GBM Glomerulonephritis

Session Information

• Glomerular Diseases: Immunology, Inflammation - II
  November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1202 Glomerular Diseases: Immunology and Inflammation

Author

• Shi, Yue, Peking University First Hospital, Beijing, China

Yue Shi,

Background

P14 (α3_127-148) was a nephritogenic epitope on human α3(IV)NC1, inducing EAG with its core motif W₁₃₆I₁₃₇L₁₃₉W₁₄₀G₁₄₂F₁₄₃F₁₄₅. Based on the sequences of α1-P14 and α3-P14, a modified peptide (m-P14) was designed by the substitution of α3-I₁₃₇ to α1-S₁₃₇ .

Methods

m-P14 was injected into P14-immunized WKY rats either on immunization or upon disease onset.PAS staining, ELISA, Flow cytometry, ELISpot were also applied in this study.

Results

m-P14 intervention attenuated the α3-P14 induced anti-GBM disease in early-treatment groups and treatment group with decreased crescent formation(30mg/kg m-P14: 0.5±0.4 vs. 68.8±15.4 %; P=0.002; 10mg/kg m-P14: 6.3±5.6 vs. 68.8±15.4%, P=0.009; treatment: 20.1±8.4 vs. 68.8±15.4%, P=0.026). m-P14 could inhibited the binding of α3-P14 to MHC molecules and abated the forming of splenic Th17 in intervention groups. m-P14 also inhibited the binding between α3-P14 to antibodies and impeded intra-molecular epitope spreading.

Conclusion

m-P14 could arrest and attenuate the kidney injuries of anti-GBM disease in rat model through cellular and humoral immunity regulation. This approach confirmed the feasibility of modulating T cell activation for the treatments of Goodpasture’s disease.

The design of m-P14 and the flowcharts of m-P14 intervention in experimental anti-GBM disease.

Early-treatment and treatment of m-P14 in experimental anti-GBM glomerulonephritis.