EXPLORING CXCL13 LEVELS IN ACUTE ANTIBODY-MEDIATED REJECTION IN RENAL TRANSPLANTATION: AN INTEGRATED EXPERIMENTAL AND BIOINFORMATICS APPROACH

 
EXPLORING CXCL13 LEVELS IN ACUTE ANTIBODY-MEDIATED REJECTION IN RENAL TRANSPLANTATION: AN INTEGRATED EXPERIMENTAL AND BIOINFORMATICS APPROACH
Carlos A.
Guzmán-Martín
Iván Zepeda-Quiroz ivanquiroz621@gmail.com Instituto Nacional de Cardiología Ignacio Chávez Departamento de Nefrología Ciudad de México
José Salvador López-Gil salvadorlgil@gmail.com Instituto Nacional de Cardiología Ignacio Chávez Departamento de Nefrología CDMX
José Daniel Juárez-Villa daniel_00_5@hotmail.com Instituto Nacional de Cardiología Ignacio Chávez Departamento de Nefrología CDMX
Cesar Flores-Gama cesarfloresgama@gmail.com Instituto Nacional de Cardiología Ignacio Chávez Departamento de Nefrología CDMX
Yaneli Juárez-Vicuña yaneli2608@hotmail.com Instituto Nacional de Cardiología Ignacio Chávez Departamento de Inmunología CDMX
Fausto Sánchez-Muñoz fausto22@yahoo.com Instituto Nacional de Cardiología Ignacio Chávez Departamento de Inmunología CDMX
 
 
 
 
 
 
 
 
 

Introduction: Chemokines are pivotal in orchestrating inflammatory and immune responses. Among them, C-X-C family chemokines, such as CXCL13, serve as potent chemoattractants for both follicular helper B and T cells. Competing endogenous RNA (ceRNA) networks, involving various RNA types like mRNAs, lncRNAs, and miRNAs, play a crucial role in regulating cellular functions and explaining distinct pathological conditions. Despite their potential, the use of CXCL13 and ceRNA networks for understanding Acute Antibody-Mediated Rejection (ABMR) in renal transplantation remains underexplored.

Material and methods: We enrolled 42 participants, comprising 27 renal transplantation (RT) patients—15 with ABMR and 12 without ABMR, along with 15 healthy controls. We quantified circulating CXCL13 levels using ELISA. Bioinformatics analysis of the ceRNA network was conducted using STRING and miRNET.ca software.

Figure 1. Serum levels of CXCL13. (a) Serum levels comparison between controls and renal transplant patients. (b) Higher serum levels of CXCL13 in transplant patients with ABMR. (c) Discriminative value of CXCL13 for ABMR. Mann Whitney-U and AUC ROC analysis were performed.Results: Our findings revealed significantly elevated CXCL13 levels in RT patients compared to the control group (median: 82.41, 95% CI: 60.23-159.4 vs. median: 63.86, 95% CI: 45.72-88.06, p=0.0318). Furthermore, ABMR patients exhibited higher CXCL13 levels compared to those without rejection (median: 116.7, CI: 76.36-221.9 vs. median: 61.44, CI: 55.19-118.1, p=0.0272). The Area Under the Curve (AUC) analysis confirmed the discriminatory potential of CXCL13 between ABMR and non-ABMR patients (AUC: 0.7639, 95% CI: 0.5707-0.9570, p=0.0282). Additionally, ceRNA analysis unveiled intriguing miRNAs, genes, and lncRNAs possibly involved in the context of ABMR.

Conclusion: Our study indicates that RT patients with ABMR exhibit elevated circulating CXCL13 levels compared to those without rejection, suggesting its clinical relevance and diagnostic utility for ABMR. Moreover, CXCL13 may be associated with various genes, miRNAs, and lncRNAs, potentially serving as future therapeutic targets in the management of ABMR.

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