Upregulated Expression of Janus Kinase Genes in T Cell-Mediated Acute Kidney Allograft Rejection

Abstract

Background: T-cell-mediated acute kidney transplant rejection (TCMR) is a post-transplantation complication characterized by the infiltration of immune cells into the tissue and sudden dysfunction of the allograft. To develop effective diagnostic and therapeutic methods, it is crucial to understand the molecular mechanisms involved in the initiation and progression of TCMR. Janus kinase (JAK) enzymes, which are involved in proinflammatory cytokine signal transduction, may play a role in TCMR. Given the recent development of JAK inhibitors, the role of JAK molecules should be explored to determine whether they could be potential targets for the treatment of TCMR. Objectives: The study aimed to compare the relative expression of JAK-1, JAK-2, and JAK-3 genes between patients diagnosed with TCMR and stable recipients. Methods: The expression of JAK-1, JAK-2, and JAK-3 genes was evaluated in peripheral blood monocytes of 30 patients with TCMR and 30 stable patients using the RT-PCR method. Results: Janus kinase-1 gene expression in TCMR patients was significantly higher compared to stable patients (P-value = 0.02). However, the relative expression of JAK-2 and JAK-3 genes was comparable between the two groups. Additionally, there was a negative correlation between JAK-1 and JAK-3 gene expression and the estimated glomerular filtration rate in the studied population (P-value = 0.01 and 0.029, respectively). Conclusions: Janus kinase-1 gene expression increased significantly during TCMR of the kidney transplant. Therefore, specific inhibition of this molecule by JAK inhibitor drugs might be considered a therapeutic option for treating TCMR.