The Transcriptomic Analysis Revealed a Clear Deregulation of the C1QB Gene in Peripheral Blood Mononuclear Cells of Renal Transplant Patients with Chronic Antibody Mediated Rejection
1Department of Medicine, Renal Unit, University/Hospital of Verona, Verona, Italy, 2Department of Emergency and Organ Transplantation-Nephrology Unit, University of Bari, Bari, Italy, 3Nephrology, Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy, 4Università Cattolica del Sacro Cuore, Roma, Italy
Meeting: 2020 American Transplant Congress
Abstract number: A-325
Keywords: Gene expression, Kidney transplantation
Session Information
Session Name: Poster Session A: Biomarker Discovery and Immune Modulation
Session Type: Poster Session
Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
Location: Virtual
*Purpose: Chronic antibody-mediated rejection (CAMR) is a multi-factorial pathological condition that can affect more that 40-50% of kidney transplanted recipients. Its clinical evolution is often silent and this can delay its diagnosis. Additionally, although there have been many advances in understanding the biological mechanisms underlying its onset, there are no non-invasive biomarkers that can identify patients at risk of developing this complication at early stage.
*Methods: By a microarray methodology (Agilent technology), we analyzed the transcriptomic profile of peripheral blood mononuclear cells (PBMCs) isolated from 10 patients with CAMR diagnosed according to the current BANFF criteria (n: 10) and 10 patients with normal-functioning graft (controls). For the bioinformatics analysis we used both the ANOVA and the Kruskal-Wallis tests adjusted for multiple-testing. Subsequently, a Weighted Gene Correlation Network Analysis (WGCNA) was employed to select those genes biologically co-expressed/linked.
*Results: 935 genes were differentially expressed between the two groups, demonstrating the great impact of this pathological condition on the circulating immune-inflammatory system but, after WGCNA co-expression analysis, a group of genes (enclosed in a single co-expression module, 13 genes) appeared highly discriminating CAMR versus Controls (p<5.2 e-7). This module included: Interferon-induced transmembrane proteins (IFITM) 2, 3, 4. However, the most discriminative gene between CAMR versus controls was C1QB (Complement component 1, q subcomponent, B chain, p<0.001), a key element of the classical complement pathway. ELISA validated transcriptomic results.
*Conclusions: Our study confirmed the role of the interferon pathway and revealed a systemic activation of the complement system in CAMR. Finally, it suggested that C1QB could represent, if validated in a larger cohort of patients, an efficient molecular diagnostic biomarker for this important complication.
To cite this abstract in AMA style:
Zaza G, Granata S, Santoro G, Caletti C, Pontrelli P, Rascio F, Rossi M, Andrighetto S, Grandaliano G. The Transcriptomic Analysis Revealed a Clear Deregulation of the C1QB Gene in Peripheral Blood Mononuclear Cells of Renal Transplant Patients with Chronic Antibody Mediated Rejection [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/the-transcriptomic-analysis-revealed-a-clear-deregulation-of-the-c1qb-gene-in-peripheral-blood-mononuclear-cells-of-renal-transplant-patients-with-chronic-antibody-mediated-rejection/. Accessed May 11, 2025.« Back to 2020 American Transplant Congress