A connection from CCR5 blockade, Maraviroc, and ferroptosis in kidney transplants.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9639483/
“Five diagnostic genes were further identified, including CCR5, CD86, CD8A, ITGAM, and PTPRC, which were positively correlated with allograft rejection after the kidney transplant. Highly infiltrated immune cells, highly expression of hypoxia-related genes and activated status of EMT were significantly positively correlated with five diagnostic genes. Interestingly, suppressors of ferroptosis (SOFs) and drivers of ferroptosis (DOFs) showed a complex regulatory relationship between ferroptosis and five diagnostic genes. CD86, CCR5, and ITGAM were respectively drug target of ABATACEPT, MARAVIROC, and CLARITHROMYCIN. PTPRC was drug target of both PREDNISONE and EPOETIN BETA. In conclusion, the study could be useful in understanding changes in the microenvironment within transplantation, which may promote or sustain the development of allograft rejection after kidney transplantation.”
“Activation of the immune system in recipients is majorly responsible for allograft rejection [4,5]. The severity of the allograft dysfunction process is positively correlated with the incidence of T cell-mediated acute rejection”
“Ferroptosis, characterized by membrane damage, is an iron-dependent and regulated cell death [14]. Ferroptosis-related indicators, including iron and lipid peroxides are associated with renal fibrosis”
Wikipedia…
“In general, when transplanting tissue or cells from a genetically different donor to the graft recipient, the alloantigen of the donor induces an immune response in the recipient against the graft. This response can destroy the graft if not controlled. The whole process is called allograft rejection.”
Furthermore…
https://web.archive.org/web/20200227074109id_...117-043720
“Abstract
Allogeneic transplantation of foreign organs or tissues has lifesaving po- tential, but can lead to serious complications. After solid organ transplan- tation, immune-mediated rejection mandates the use of prolonged global immunosuppression and limits the life span of transplanted allografts. Af- ter bone marrow transplantation, donor-derived immune cells can trigger life-threatening graft-versus-host disease. T cells are central mediators of alloimmune complications and the target of most existing therapeutic in- terventions. We review recent progress in identifying multiple cell types in addition to T cells and new molecular pathways that regulate pathogenic alloreactivity. Key discoveries include the cellular subsets that function as potential sources of alloantigens, the cross talk of innate lymphoid cells with damaged epithelia and with the recipient microbiome, the impact of the alarmin interleukin-33 on alloreactivity, and the role of Notch ligands ex- pressed by fibroblastic stromal cells in alloimmunity. While refining our un- derstanding of transplantation immunobiology, these findings identify new therapeutic targets and new areas of investigation.”
My conclusion…
Considering in kidney transplants…
“If leaving unchecked, allograft rejection reaction can destroy the graft. With the use of immunosuppressive agents, the incidence of transplant rejection has reduced [2]. Although the annual survival rate of kidney transplant has reached more than 90%, there is a 4–5% loss of function of the kidney graft. The 5-year survival rate of kidney transplant is 70%, whereas the 10-year survival rate is only 50% [2]. Regular monitoring of serum creatinine is an insensitive predictor and only increases upon the deficiency in kidney function [3]. Thus, it is important to identify potential diagnostic and therapeutic markers that associated with different molecular mechanisms in the process of allograft rejection in kidney transplant patients.”
My conclusion is that the use of immune suppressing drugs to halt allograft rejection, GvHD, bone marrow, other organs etc is an ongoing and successful method of longer survival after grafting a foreign tissue, organ, or cell.
The real deal is this concerning immune suppression is immune modulation is better. No disease onsets caused by suppressing immune system if done gracefully.
That’s what Leronlimab does. Doesn’t suppress. Modulates.
Anything Maraviroc can do we can do better.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9639483/
“Five diagnostic genes were further identified, including CCR5, CD86, CD8A, ITGAM, and PTPRC, which were positively correlated with allograft rejection after the kidney transplant. Highly infiltrated immune cells, highly expression of hypoxia-related genes and activated status of EMT were significantly positively correlated with five diagnostic genes. Interestingly, suppressors of ferroptosis (SOFs) and drivers of ferroptosis (DOFs) showed a complex regulatory relationship between ferroptosis and five diagnostic genes. CD86, CCR5, and ITGAM were respectively drug target of ABATACEPT, MARAVIROC, and CLARITHROMYCIN. PTPRC was drug target of both PREDNISONE and EPOETIN BETA. In conclusion, the study could be useful in understanding changes in the microenvironment within transplantation, which may promote or sustain the development of allograft rejection after kidney transplantation.”
“Activation of the immune system in recipients is majorly responsible for allograft rejection [4,5]. The severity of the allograft dysfunction process is positively correlated with the incidence of T cell-mediated acute rejection”
“Ferroptosis, characterized by membrane damage, is an iron-dependent and regulated cell death [14]. Ferroptosis-related indicators, including iron and lipid peroxides are associated with renal fibrosis”
Wikipedia…
“In general, when transplanting tissue or cells from a genetically different donor to the graft recipient, the alloantigen of the donor induces an immune response in the recipient against the graft. This response can destroy the graft if not controlled. The whole process is called allograft rejection.”
Furthermore…
https://web.archive.org/web/20200227074109id_...117-043720
“Abstract
Allogeneic transplantation of foreign organs or tissues has lifesaving po- tential, but can lead to serious complications. After solid organ transplan- tation, immune-mediated rejection mandates the use of prolonged global immunosuppression and limits the life span of transplanted allografts. Af- ter bone marrow transplantation, donor-derived immune cells can trigger life-threatening graft-versus-host disease. T cells are central mediators of alloimmune complications and the target of most existing therapeutic in- terventions. We review recent progress in identifying multiple cell types in addition to T cells and new molecular pathways that regulate pathogenic alloreactivity. Key discoveries include the cellular subsets that function as potential sources of alloantigens, the cross talk of innate lymphoid cells with damaged epithelia and with the recipient microbiome, the impact of the alarmin interleukin-33 on alloreactivity, and the role of Notch ligands ex- pressed by fibroblastic stromal cells in alloimmunity. While refining our un- derstanding of transplantation immunobiology, these findings identify new therapeutic targets and new areas of investigation.”
My conclusion…
Considering in kidney transplants…
“If leaving unchecked, allograft rejection reaction can destroy the graft. With the use of immunosuppressive agents, the incidence of transplant rejection has reduced [2]. Although the annual survival rate of kidney transplant has reached more than 90%, there is a 4–5% loss of function of the kidney graft. The 5-year survival rate of kidney transplant is 70%, whereas the 10-year survival rate is only 50% [2]. Regular monitoring of serum creatinine is an insensitive predictor and only increases upon the deficiency in kidney function [3]. Thus, it is important to identify potential diagnostic and therapeutic markers that associated with different molecular mechanisms in the process of allograft rejection in kidney transplant patients.”
My conclusion is that the use of immune suppressing drugs to halt allograft rejection, GvHD, bone marrow, other organs etc is an ongoing and successful method of longer survival after grafting a foreign tissue, organ, or cell.
The real deal is this concerning immune suppression is immune modulation is better. No disease onsets caused by suppressing immune system if done gracefully.
That’s what Leronlimab does. Doesn’t suppress. Modulates.
Anything Maraviroc can do we can do better.
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