AIM2 as a putative target in acute kidney graft rejection

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN IMMUNOLOGY; v. 13, p. 15-pg., 2022-09-30.

Resumo

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)

• Processo FAPESP: 19/22409-4 - Papel do acetato na dinâmica e disfunção mitocondrial na lesão renal induzida por isquemia e reperfusão
• Beneficiário: João Vitor Ziroldo Lopes
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 18/21844-6 - Metabolismo celular e dinâmica mitocondrial em rins submetidos à lesão de isquemia e reperfusão: um papel para a heme oxigenase 1
• Beneficiário: Nathalia Franchon Marques Tejada
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 17/05264-7 - Metabolismo celular, microbiota e sistema imune: novos paradigmas na fisiopatologia das doenças renais
• Beneficiário: Niels Olsen Saraiva Câmara
• Modalidade de apoio: Auxílio à Pesquisa - Temático