The Effects of Clazakizumab on Peripheral Blood and Kidney Transcriptomes in Patients With Late Antibody-Mediated Rejection.

ABSTRACT:

Introduction

There are no licensed treatments for antibody-mediated rejection (AMR), a major cause of late kidney allograft loss. Clazakizumab (CLZ), an interleukin (IL)-6-neutralizing antibody, showed potential efficacy in a phase 2 trial in late AMR, with a reduction in donor-specific antibodies (DSAs) and kidney molecular microscope diagnostic system (MMDx) AMR score, but the underpinning mechanisms are unclear.

Methods

Using peripheral blood transcriptomics, we identified a decrease in IL-6-associated "JAK-STAT signaling" pathway genes with CLZ, and a reduction in gene modules that enriched for T follicular helper cell and activated platelet signatures, cells that contribute to DSA generation and inflammatory responses to DSA respectively. However, responses were variabl

SUBMITTER: Zhang R 

PROVIDER: S-EPMC12640031 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature