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Reply to Comment on "Clazakizumab in the treatment of chronic active antibody-mediated kidney transplant rejection: Results from the IMAGINE phase 3, randomized, double-blind, placebo-controlled study".

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Activity-based Protein Profiling Approaches for Transplantation.

Mario Navarrete1,2, John A Wilkins1,2, Ying Lao1,2

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Activity-based protein profiling (ABPP) reveals active enzymes, offering new insights into transplant rejection. This chemical proteomic method aids in developing diagnostics and therapeutics by measuring enzyme activity, not just quantity.

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Area of Science:

  • Proteomics
  • Biochemistry
  • Transplantation Research

Background:

  • Enzyme activity is crucial in pathophysiology, often more so than enzyme quantity.
  • Traditional proteomics cannot detect enzyme activity changes due to conformational shifts.
  • Enzyme activity reflects rapid physiological responses to inflammation/injury, independent of protein synthesis.

Purpose of the Study:

  • To provide an overview of Activity-Based Protein Profiling (ABPP) for transplantation research.
  • To detail the rationale, methods, challenges, and applications of ABPP.
  • To illustrate ABPP's utility with a case study in kidney transplant rejection.

Main Methods:

  • Activity-based protein profiling (ABPP) uses chemical probes to identify active enzymes.
  • ABPP targets diverse enzyme families like serine hydrolases, proteases, and deacetylases.
  • A urine serine hydrolase ABPP case example in kidney transplant rejection is presented.

Main Results:

  • ABPP provides a novel dimension for characterizing dynamic changes in clinical samples.
  • The approach identifies and quantifies relevant enzyme activities.
  • Enzyme activity profiling offers opportunities for understanding disease processes.

Conclusions:

  • ABPP enhances understanding of pathophysiological processes leading to transplant dysfunction.
  • ABPP can identify biomarkers for disease activity, aiding diagnostics and real-time monitoring.
  • Insights from ABPP can guide the development of novel enzyme-specific transplant therapeutics.