Pre-transplant T-cell Clonality

Jones, Stephen L.; Moore, Linda W.; Li, Xian Chang; Mobley, Constance M.; Fields, Paul A.; Graviss, Edward A.; Nguyen, Duc T.; Fong, Joy Nolte; Saharia, Ashish; Hobeika, Mark J.; McMillan, Robert; Victor, David W.; Minze, Laurie J.; Gaber, A. Osama; Ghobrial, R. Mark

doi:10.1097/sla.0000000000004998

Cited by 4 publications

(1 citation statement)

References 43 publications

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“…These infections often manifest as severe mixed infections involving fungi, bacteria, and viruses, which can progress to sepsis. Sepsis represents the most lethal infectious disease and contributes signi cantly to mortality rates in LT patients [7,8]. Kim et al reported that bacteremia developed in 24% of LT recipients [9].…”

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confidence: 99%

Epidemiology, antimicrobial resistance and risk factors of infection among liver transplant patients in East China: a retrospective study 2010 to 2023

Wang,

Jiang,

Liao

et al. 2024

Preprint

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Background Liver transplantation (LT) recipients exhibit heightened susceptibility to infection and sepsis, which have emerged as the most prevalent and life-threatening complications significantly impacting prognosis. The etiological spectrum of organisms following LT has undergone substantial changes over recent decades. Methods This retrospective monocentric study included a consecutive cohort of 776 LT patients from 2010 to 2023, in contrast to our previous study conducted from 2007 to 2010. Infection was diagnosed as per the established definition, and sepsis was diagnosed based on the sepsis-3 criteria. Infection was diagnosed as per the established definition, and sepsis was diagnosed based on the sepsis-3 criteria. Samples were collected from infection sites, cultured, and isolated for further analysis. Results A total of 207 pathogens were isolated from 180 infection sites of 156 (20.1%) patients, comprising of 82 (39.6%) gram-positive bacteria, 90 (43.5%) gram-negative bacteria, and 35 (16.9%) fungi. Among the gram-positive bacteria, we identified Methicillin-resistant Staphylococcus aureus (MRSA) in 18 cases, Methicillin-resistant coagulase-negative staphylococci (MRCNS) in 25 cases, and Vancomycin-resistant Enterococcus faecium (VRE) in 1 case. In terms of gram-negative bacteria, Carbapenem-resistant Enterobacteriaceae (CRE) was found in 8 cases (7 Klebsiella pneumoniae and 1 Escherichia coli), Extended-spectrum beta-lactamases (ESBLs)-producing bacteria were detected in 7 cases (5 Escherichia coli and 2 Enterobacter cloacae), Carbapenem-resistant Acinetobacter baumannii (CRAB) was found in 14 cases, and 2 cases had Carbapenem-resistant Pseudomonas aeruginosa (CRPA). Advanced age, prolonged mechanical ventilation, and extended ICU stay were significantly associated with increased susceptibility to post-LT infections. Infected patients with bilirubin levels exceeding 90 μmol/L (OR 3.46, 95% CI 1.46-8.24; P = 0.005) as well as drug-resistance bacterial infections (OR 2.35, 95% CI 1.07-5.15; P = 0.033) were more likely to develop sepsis. Conclusions More than 45% of bacterial infections were caused by drug-resistant pathogens, with over 30% of gram-negative bacteria exhibiting carbapenem resistance. Implementation of strategies aimed at reducing the duration of mechanical ventilation and ICU stay may effectively decrease the incidence of post-liver transplantation infection. Furthermore, pre-transplant interventions targeting reduction in jaundice could potentially mitigate the risk of post-transplant sepsis.

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Epidemiology, antimicrobial resistance and risk factors of infection among liver transplant patients in East China: a retrospective study 2010 to 2023

Wang,

Jiang,

Liao

et al. 2024

Preprint

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Hepatic pannexin‐1 mediates ST2⁺ regulatory T cells promoting resolution of inflammation in lipopolysaccharide‐induced endotoxemia

Wang

Shi

Wang

et al. 2022

Clinical & Translational Med

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Sepsis remains the most lethal infectious disease and substantially impairs patient prognosis after liver transplantation (LT). Our previous study reported a role of the pannexin 1 (PANX1)–interleukin‐33 (IL‐33) axis in activating innate immunity to protect against methicillin‐resistant Staphylococcus aureus infection; however, the role of PANX1 in regulating adaptive immunity in sepsis and the underlying mechanism are unclear. In this study, we examined the role of the PANX1–IL‐33 axis in protecting against sepsis caused by a gram‐negative bacterial infection in an independent LT cohort. Next, in animal studies, we assessed the immunological state of Panx1−/‐ mice with lipopolysaccharide (LPS)‐induced endotoxemia and then focused on the cytokine storm and regulatory T cells (Tregs), which are crucial for the resolution of inflammation. To generate liver‐specific Panx1‐deficient mice and mimic clinical LT procedures, a mouse LT model was established. We demonstrated that hepatic PANX1 deficiency exacerbated LPS‐induced endotoxemia and dysregulated the immune response in the mouse LT model. In hepatocytes, we confirmed that PANX1 positively regulated IL‐33 synthesis after LPS administration. We showed that the adenosine triphosphate‐P2X7 pathway regulated the hepatic PANX1–IL‐33 axis during endotoxemia in vitro and in vivo. Recombinant IL‐33 treatment rescued LPS‐induced endotoxemia by increasing the numbers of liver‐infiltrating ST2+ Tregs and attenuating the cytokine storm in hepatic PANX1‐deficient mice. In conclusion, our findings revealed that the hepatic PANX1–IL‐33 axis protects against endotoxemia and liver injury by targeting ST2+ Tregs and promoting the early resolution of hyperinflammation.

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Clinical application of immune repertoire sequencing in solid organ transplant

et al. 2023

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BackgroundMeasurement of T cell receptor (TCR) or B cell receptor (BCR) gene utilization may be valuable in monitoring the dynamic changes in donor-reactive clonal populations following transplantation and enabling adjustment in therapy to avoid the consequences of excess immune suppression or to prevent rejection with contingent graft damage and to indicate the development of tolerance.ObjectiveWe performed a review of current literature to examine research in immune repertoire sequencing in organ transplantation and to assess the feasibility of this technology for clinical application in immune monitoring.MethodsWe searched MEDLINE and PubMed Central for English-language studies published between 2010 and 2021 that examined T cell/B cell repertoire dynamics upon immune activation. Manual filtering of the search results was performed based on relevancy and predefined inclusion criteria. Data were extracted based on study and methodology characteristics.ResultsOur initial search yielded 1933 articles of which 37 met the inclusion criteria; 16 of these were kidney transplant studies (43%) and 21 were other or general transplantation studies (57%). The predominant method for repertoire characterization was sequencing the CDR3 region of the TCR β chain. Repertoires of transplant recipients were found to have decreased diversity in both rejectors and non-rejectors when compared to healthy controls. Rejectors and those with opportunistic infections were more likely to have clonal expansion in T or B cell populations. Mixed lymphocyte culture followed by TCR sequencing was used in 6 studies to define an alloreactive repertoire and in specialized transplant settings to track tolerance.ConclusionMethodological approaches to immune repertoire sequencing are becoming established and offer considerable potential as a novel clinical tool for pre- and post-transplant immune monitoring.

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Pre-transplant T-cell Clonality

Abstract: Supplemental Digital Content is available in the text

Cited by 4 publications

References 43 publications

Epidemiology, antimicrobial resistance and risk factors of infection among liver transplant patients in East China: a retrospective study 2010 to 2023

Epidemiology, antimicrobial resistance and risk factors of infection among liver transplant patients in East China: a retrospective study 2010 to 2023

Hepatic pannexin‐1 mediates ST2⁺ regulatory T cells promoting resolution of inflammation in lipopolysaccharide‐induced endotoxemia

Clinical application of immune repertoire sequencing in solid organ transplant

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Pre-transplant T-cell Clonality

Abstract: Supplemental Digital Content is available in the text

Cited by 4 publications

References 43 publications

Epidemiology, antimicrobial resistance and risk factors of infection among liver transplant patients in East China: a retrospective study 2010 to 2023

Epidemiology, antimicrobial resistance and risk factors of infection among liver transplant patients in East China: a retrospective study 2010 to 2023

Hepatic pannexin‐1 mediates ST2+ regulatory T cells promoting resolution of inflammation in lipopolysaccharide‐induced endotoxemia

Clinical application of immune repertoire sequencing in solid organ transplant

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Hepatic pannexin‐1 mediates ST2⁺ regulatory T cells promoting resolution of inflammation in lipopolysaccharide‐induced endotoxemia