AIM2 as a putative target in acute kidney graft rejection

Author(s)

Tejada, Nathalia Franchon Marques ; Lopes, Joao Vitor Ziroldo ; da Goncalves, Luis Eduardo Duarte ; da Conceicao, Izabela Mamede Costa Andrade ; Franco, Gloria Regina ; Ghirotto, Bruno ; Camara, Niels Olsen Saraiva

• Document type: Journal article
• Source: FRONTIERS IN IMMUNOLOGY; v. 13, p. 15-pg., 2022-09-30.

Abstract

Acute rejection (AR) is a process triggered via the recognition of grafted organ-derived antigens by the immune system, which could present as a life-threatening condition. In the context of a kidney transplant, despite improvement with immunosuppressive therapies, AR maintains a significant incidence of 10%, and currently available drugs generally act in similar and canonical pathways of lymphocyte activation. This prompted the research for different approaches to identify potential novel targets that could improve therapeutic interventions. Here, we conducted a transcriptome analysis comparing groups of acute rejection (including T cell-mediated rejection and antibody-mediated rejection) to stable grafts that included differentially expressed genes, transcription factor and kinase enrichment, and Gene Set Enrichment Analysis. These analyses revealed inflammasome enhancement in rejected grafts and AIM2 as a potential component linked to acute rejection, presenting a positive correlation to T-cell activation and a negative correlation to oxidative phosphorylation metabolism. Also, the AIM2 expression showed a global accuracy in discerning acute rejection grafts (area under the curve (AUC) = 0.755 and 0.894, p < 0.0001), and meta-analysis comprising different studies indicated a considerable enhancement of AIM2 in rejection (standardized mean difference (SMD) = 1.45, [CI 95%, 1.18 to 1.71]), especially for T cell-mediated rejection (TCMR) (SMD = 2.01, [CI 95%, 1.58 to 2.45]). These findings could guide future studies of AIM2 as either an adjuvant target for immunosuppression or a potential biomarker for acute rejection and graft survival. (AU)

• FAPESP's process: 19/22409-4 - Role of acetate in ischemia and reperfusion-induced mitochondrial injury and renal injury
• Grantee: João Vitor Ziroldo Lopes
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 18/21844-6 - Cell metabolism and mitochondrial dynamics in kidney ischemia-reperfusion injury: a role for heme oxygenase 1
• Grantee: Nathalia Franchon Marques Tejada
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 17/05264-7 - Cell metabolism, microbiota and immune system: new paradigms in renal diseases physiopathology
• Grantee: Niels Olsen Saraiva Câmara
• Support Opportunities: Research Projects - Thematic Grants