Role of Complement Activation in Allograft Inflammation

AbstractPurpose of ReviewNovel paradigms have broadened our understanding of mechanisms through which complement mediates allograft inflammation/injury. Herein, we review advances in the field and highlight therapeutic implications.Recent FindingsPre-clinical and translational human trials have elucidated complement-dependent mechanisms of post-transplant ischemia-reperfusion (I/R) injury. Immune cell-derived, and intracellular, complement activation is newly linked to proinflammatory T cell immunity relevant to allograft rejection. Complement-induced immune regulation, including C5a ligation of C5a receptor 2 on T cells, C5a/C5a receptor 1 interactions on regulatory myeloid cells, and C1q binding to CD8+ T cells, can inhibit proinflammatory T cells and/or prolong murine allograft survival. Pilot trials of complement inhibition to treat/prevent human I/R- or antibody-initiated allograft injury show promise.SummaryThe complement system participates in allograft injury through multiple context-dependent mechanisms involving various components and receptors. These new insights along with development and implementation of individualized complement inhibitory strategies have potential to improve transplant outcomes.
Source: Current Transplantation Reports - Category: Transplant Surgery Source Type: research

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ConclusionsProlonged use of cyclosporine may expose to several dose-related adverse events and may contribute to the development of allograft dysfunction but it does not necessarily cause relentless, progressive transplant failure if patients are carefully and consistently monitored during the follow-up.
Source: Clinical and Experimental Nephrology - Category: Urology & Nephrology Source Type: research
ConclusionsRates of ODD utilization in lung transplantation have increased in accordance with the opioid epidemic, but there remains a significant pool of ODD pulmonary allografts with favorable characteristics that are discarded. With no significant difference in survival between ODD and non-ODD recipients, further expansion of this donor pool may be appropriate and pulmonary allografts should not be discarded based solely on ODD status.
Source: The Annals of Thoracic Surgery - Category: Cardiovascular & Thoracic Surgery Source Type: research
A major obstacle in kidney transplantation for primary focal segmental glomerulosclerosis (FSGS) is the risk of disease recurrence. Recurrent FSGS affects up to 60% of first kidney grafts and exceeds 80% in patients who have lost their first graft due to recurrent FSGS. Clinical and experimental evidence support the hypothesis that a circulating permeability factor is the mediator in the pathogenesis of primary and recurrent disease. Despite all efforts, the causing agent has not yet been identified. Several treatment options for the management of recurrent FSGS have been proposed. In addition to plasma exchange, B-cell de...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
We describe here significant studies that have highlighted potential candidates for reliable and noninvasive biomarkers of CLAD in the fields of imaging and functional monitoring, humoral immunity, cell-mediated immunity, allograft injury, airway remodeling and gene expression. Such biomarkers would improve CLAD prediction and allow differential LT management regarding CLAD risk.
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions: CYP3A5 polymorphisms correlated with tacrolimus dose requirements and blood levels, incidence of early acute rejection, and tacrolimus nephrotoxicity. CYP3A5 polymorphism analysis prior to renal transplant will aid more precise early tacrolimus dose calculation to balance between rejection and toxicity.
Source: Indian Journal of Nephrology - Category: Urology & Nephrology Authors: Source Type: research
Sonia Mehrotra, Raj Kumar Sharma, Manas R PatelIndian Journal of Nephrology 2019 29(4):242-247 Vitamin-D has immuno-modulatory properties besides its role in mineral and bone disorder (MBD) and could have a role in allograft outcome. Fifty-two chronic kidney disease patients on dialysis going for transplantation were prospectively studied before and after renal transplantation. FGF23, 25(OH) vitamin D, 1,25-Dihydroxyvitamin D, PTH, serum Ca, serum PO4, and e-GFR status were evaluated. Vitamin D deficiency was seen in 25.0% of recipients before transplant (26.09 ± 12.19 ng/mL) and in 48.1% at 6 months post-tra...
Source: Indian Journal of Nephrology - Category: Urology & Nephrology Authors: Source Type: research
J reconstr Microsurg DOI: 10.1055/s-0039-1693455 Background Prolonged cold ischemia associated with static cold storage (SCS) results in higher incidence of acute and chronic allograft rejection in solid organ transplantations. Deleterious effects of SCS on vascularized composite tissue allograft were studied with limited data on muscle structure and function. The aim of this study is to evaluate the long-term impact of SCS on muscle metabolism, structure, and force generation using a syngeneic rat hindlimb transplantation model. Methods Sixty-five male Lewis rats (250 ± 25 g) we...
Source: Journal of Reconstructive Microsurgery - Category: Surgery Authors: Tags: Original Article Source Type: research
Conclusion: Urinary TG2 in early posttransplant periods is a potent biomarker for kidney allograft inflammation or fibrosis. PMID: 31297350 [PubMed]
Source: Annals of Surgical Treatment and Research - Category: Surgery Tags: Ann Surg Treat Res Source Type: research
ConclusionSequential monitoring of uKIM-1 mRNA expression level and its protein concentration in the serum and urine samples of renal transplant patients suggests that KIM-1 could be a sensitive and specific biomarker for early diagnosis and prognosis of kidney allograft injury.
Source: Clinical and Experimental Nephrology - Category: Urology & Nephrology Source Type: research
Publication date: Available online 12 July 2019Source: Journal of Clinical and Experimental HepatologyAuthor(s): Prafulla Vishnurao Jadhav, Kothakota Sunil Raviraj, Madhu Sasidharan, Harish Kareem, Ajith K. NairAbstractIntroductionIschemic reperfusion injury (IRI) is an important complication of liver transplant (LT). The donor risk index (DRI), which does not incorporate steatosis, includes several variables known to impact on allograft survival. The purpose of this study was to report on donor liver allograft steatosis and its association with severity of IRI.AimTo determine effect of type and grade of donor liver steato...
Source: Journal of Clinical and Experimental Hepatology - Category: Gastroenterology Source Type: research
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