| خلاصه مقاله | Felzartamab, a CD38 monoclonal antibody, suppresses antibody-mediated rejection (ABMR) in
kidney transplant patients but often leads to recurrence post-treatment. It reduces ABMR
molecular activity, primarily targeting interferon gamma-inducible and NK cell transcripts, with
minimal effect on endothelial transcripts. Suppression is incomplete in severe cases, and molecular
recurrence is common by week 52. However, felzartamab shows parenchymal benefits, slowing
kidney injury progression beyond treatment, suggesting potential long-term protective effects. To
determine the molecular effects of 6 months of felzartamab treatment, genome-wide microarray
analysis was performed on trial biopsies, comparing pre-treatment, end-of-treatment (week 24),
and post-treatment (week 52) samples from 10 felzartamab and 10 placebo patients. Data no.
GSE275824 were obtained from the GEO database, and the expression dataset was downloaded
from pre-treatment, end-of-treatment (week 24), and post-treatment (week 52) samples. The data
were analyzed with the GEO2R analysis program. As a result, differentially expressed genes that
play roles were excluded. Gene ontology and pathway analysis of these genes were carried out
with DAVID software. For the analysis of prominent genes, STRING software was used. In the
validation of hub genes, genes were determined using the mcode and cytohubba attachments of
the CYTOSCAPE software. We investigated significant downregulated DEGs (1031 baseline, 592
24week and 717 52 weeks down-regulated) and upregulated DEGs (900 baseline, 653 24week and
1428 52 weeks down-regulated). In gene ontology, it was observed that genes were collected in
endoplasmic reticulum membrane, membrane, RNA polymerase II cis-regulatory region
sequence-specific DNA binding, Golgi membrane, regulation of transcription by RNA polymerase
II, DNA-binding transcription factor activity, RNA polymerase II-specific, plasma membrane,
adaptive immune response, extracellular region, collagen-containing extracellular matrix. Based
on the Cytoscape analysis, HLA-A, HLA-B, HLA-C, HLA-E, HLA-F, PPAPDC1A, PPAPDC1B,
UQCRH, UQCRC2, COX5A, CYP4A22, RPL30, RPS20 and HIST1H3E genes were defined as
hub genes. The findings suggest that felzartamab modulates critical pathways, providing insights
into its molecular effects. Understanding these mechanisms may help identify biomarkers for
treatment response and guide the development of alternative strategies to improve long-term
kidney transplant outcomes. |