Mohammad Hossein Sharbafi1, Sara Assadiasl2, Fatemeh Pour-Reza-Gholi3, Saeed Barzegari4, Peyman Mohammadi Torbati5, Shiva Samavat3, Mohammad Hossein Nicknam1,2, Aliakbar Amirzargar1,2. 1. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 2. Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran. 3. Chronic Kidney Disease Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 4. Department of health information technology, Amol Faculty of Paramedical Sciences, Mazandaran University of Medical Sciences, Sari, Iran. 5. Department of Pathology, Labbafinejad Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Abstract
BACKGROUND: Graft rejection due to alloreactivity is still the main obstacle to successful renal transplantation. Toll-like receptors (TLRs), which are significantly involved in initiating inflammation, triggering innate immunity, occurrence of ischaemia reperfusion injury (IRI) and subsequent deterioration of allograft function, are of interest in molecular diagnosis of graft rejection. METHODS: In present research, we have evaluated the mRNA expressions of TLR-4, TLR-2 and myeloid differentiation primary response gene 88 (MyD88) in peripheral blood mononuclear cells (PBMCs) and biopsy samples of 26 stable graft function (SGF), 14 acute T-cell-mediated rejection (ACMR), six acute antibody-mediated rejection (AAMR), 10 chronic T-cell-mediated rejection (CCMR) and four chronic antibody-mediated rejection (CAMR) cases of renal transplant recipients, using TaqMan detector real-time polymerase chain reaction (RT-PCR). RESULTS: It was found that TLR4 mRNA level was significantly elevated in PBMCs of both ACMR (P.v: 0.025) and CCMR (P.v: 0.007) cases, while TLR2 gene was upregulated only in PBMCs of ACMR (P.v: 0.024). Moreover, MyD88 expression was increased in biopsy samples of all rejection groups AAMR (P.v: 0.032), ACMR (P.v: 0.002), CAMR (P.v: 0.038) and CCMR (P.v: 0.013) and could distinguish them from stable grafts with AUC (area under curve) of 0.81, 0.80, 0.83 and 0.77, respectively. CONCLUSION: These data showed that MyD88 gene upregulation in renal tissue could have diagnostic value and increased level of TLR4 mRNA in PBMCs could be suggestive of cell-mediated rejections. Therefore, monitoring the expression level of inflammatory signalling genes might be useful in predicting allograft rejection.
BACKGROUND: Graft rejection due to alloreactivity is still the main obstacle to successful renal transplantation. Toll-like receptors (TLRs), which are significantly involved in initiating inflammation, triggering innate immunity, occurrence of ischaemia reperfusion injury (IRI) and subsequent deterioration of allograft function, are of interest in molecular diagnosis of graft rejection. METHODS: In present research, we have evaluated the mRNA expressions of TLR-4, TLR-2 and myeloid differentiation primary response gene 88 (MyD88) in peripheral blood mononuclear cells (PBMCs) and biopsy samples of 26 stable graft function (SGF), 14 acute T-cell-mediated rejection (ACMR), six acute antibody-mediated rejection (AAMR), 10 chronic T-cell-mediated rejection (CCMR) and four chronic antibody-mediated rejection (CAMR) cases of renal transplant recipients, using TaqMan detector real-time polymerase chain reaction (RT-PCR). RESULTS: It was found that TLR4 mRNA level was significantly elevated in PBMCs of both ACMR (P.v: 0.025) and CCMR (P.v: 0.007) cases, while TLR2 gene was upregulated only in PBMCs of ACMR (P.v: 0.024). Moreover, MyD88 expression was increased in biopsy samples of all rejection groups AAMR (P.v: 0.032), ACMR (P.v: 0.002), CAMR (P.v: 0.038) and CCMR (P.v: 0.013) and could distinguish them from stable grafts with AUC (area under curve) of 0.81, 0.80, 0.83 and 0.77, respectively. CONCLUSION: These data showed that MyD88 gene upregulation in renal tissue could have diagnostic value and increased level of TLR4 mRNA in PBMCs could be suggestive of cell-mediated rejections. Therefore, monitoring the expression level of inflammatory signalling genes might be useful in predicting allograft rejection.
Authors: Max J M Silvis; Selma E Kaffka Genaamd Dengler; Clémence A Odille; Mudit Mishra; Niels P van der Kaaij; Pieter A Doevendans; Joost P G Sluijter; Dominique P V de Kleijn; Saskia C A de Jager; Lena Bosch; Gerardus P J van Hout Journal: Front Immunol Date: 2020-12-08 Impact factor: 7.561
Authors: Maria Teresa Rocchetti; Federica Rascio; Giuseppe Castellano; Marco Fiorentino; Giuseppe Stefano Netti; Federica Spadaccino; Elena Ranieri; Anna Gallone; Loreto Gesualdo; Giovanni Stallone; Paola Pontrelli; Giuseppe Grandaliano Journal: Int J Mol Sci Date: 2020-09-05 Impact factor: 5.923