Flow Cytometry and Solid Organ Transplantation: A Perfect Match

Maguire, Orla; Tario, Joseph D.; Shanahan, Thomas; Wallace, Paul K.; Minderman, Hans

doi:10.3109/08820139.2014.910022

Cited by 26 publications

(20 citation statements)

References 109 publications

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“…Phospho-specific flow cytometry of the intracellular signaling molecules p38MAPK, ERK and Akt is a promising technique to monitor the pharmacodynamic effects of immunosuppressive drugs in whole-blood of kidney transplant patients 27 . Previous studies on phospho-specific flow cytometry have demonstrated that TAC can inhibit p38MAPK in a dose-dependent manner in kidney transplant patients 28 .…”

Section: Introductionmentioning

confidence: 99%

Differential T Cell Signaling Pathway Activation by Tacrolimus and Belatacept after Kidney Transplantation: Post Hoc Analysis of a Randomised-Controlled Trial

Kannegieter

Hesselink

Dieterich

et al. 2017

Sci Rep

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Pharmacokinetic immunosuppressive drug monitoring poorly correlates with clinical outcomes after solid organ transplantation. A promising method for pharmacodynamic monitoring of tacrolimus (TAC) in T cell subsets of transplant recipients might be the measurement of (phosphorylated) p38MAPK, ERK1/2 and Akt (activated downstream of the T cell receptor) by phospho-specific flow cytometry. Here, blood samples from n = 40 kidney transplant recipients (treated with either TAC-based or belatacept (BELA)-based immunosuppressive drug therapy) were monitored before and throughout the first year after transplantation. After transplantation and in unstimulated samples, p-p38MAPK and p-Akt were inhibited in CD8+ T cells and p-ERK in CD4+ T cells but only in patients who received TAC-based therapy. After activation with PMA/ionomycin, p-p38MAPK and p-AKT were significantly inhibited in CD4+ and CD8+ T cells when TAC was given, compared to pre-transplantation. Eleven BELA-treated patients had a biopsy-proven acute rejection, which was associated with higher p-ERK levels in both CD4+ and CD8+ T cells compared to patients without rejection. In conclusion, phospho-specific flow cytometry is a promising tool to pharmacodynamically monitor TAC-based therapy. In contrast to TAC-based therapy, BELA-based immunosuppression does not inhibit key T cell activation pathways which may contribute to the high rejection incidence among BELA-treated transplant recipients.

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Section: Introductionmentioning

confidence: 99%

Differential T Cell Signaling Pathway Activation by Tacrolimus and Belatacept after Kidney Transplantation: Post Hoc Analysis of a Randomised-Controlled Trial

Kannegieter

Hesselink

Dieterich

et al. 2017

Sci Rep

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“…В ряде зарубежных публикаций представлены доказательства клинической информативности исследования клеточной составляющей иммунного статуса пациентов для определения лечебной тактики, режимов введения иммуносупрессивной и противоинфекционной терапии при пересадках солидных органов [9][10][11].…”

Section: Conclusion the Changes Revealed In The Cellular Component Ounclassified

Clinical significance of assessing the subpopulation composition of blood lymphocytes in patients with infectious corneal lesions in high-risk keratoplasty

Нероев

Балацкая

Chentsova

et al. 2020

Rossijskij oftalʹmologičeskij žurnal

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/л) выявлено достоверное повышение абсолютного количества дубль-позитивных Т-лимфоцитов (CD3+CD4+CD8+) по сравнению с контролем (0,009 ± 0,007 × 10 9 /л). Заключение. Выявленные изменения в клеточной составляющей иммунного статуса, общие для всех пациентов, характеризовались исключительно сдвигами Т-звена иммунитета. Индивидуальный анализ по характеру сдвигов Т-хелперов и CD4+/CD8+ в сторону повышения от нормы позволил качественно выделить III группу (с двумя и более КП). Полученные данные представляются важными для разработки критериев прогнозирования КП высокого риска и свидетельствуют о необходимости иммуносупрессии. Ключевые слова: инфекция; кератит; язвы роговицы; бельма роговицы; кератопластика высокого риска; субпопуляции лимфоцитов Конфликт интересов: отсутствует. Прозрачность финансовой деятельности: никто из авторов не имеет финансовой заинтересованности в представленных материалах или методах.

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“…To apply FCXM, donor lymphocytes and recipient serum samples were utilized. Subsequently, antihuman IgG antibodies are added and positivity is determined [10]. In addition, to add CD3 or CD19, T cells and B cells can be separated and analyzed simultaneously (Figure 2).…”

Section: Flow Cytometry Crossmatchmentioning

confidence: 99%

Donor-Specific Anti-HLA Antibodies in Organ Transplantation: Transition from Serum DSA to Intra-Graft DSA

Nakamura¹,

Ushigome²,

Shirouzu³

et al. 2019

Human Leukocyte Antigen (HLA)

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In the field of organ transplantation, donor-specific anti-HLA antibodies (DSA) have gained more popularity, as antibody-mediated rejection (AMR) has been recognized as an important factor to determine allograft survival. Thus, it is reasonable to believe that appropriate control of DSA is directly linked to well-managed immunosuppression, resulting in free from AMR. First, in order to prevent and manage AMR, it is of vital importance to be familiar with updated knowledge regarding crossmatch test and DSA detection methods, including intra-graft DSA. Second, it is also crucial to understand the standard criteria to diagnose AMR. Although pathological diagnosis and serum DSA (s-DSA) detection play the central role, the recent trend seems to be detection of intra-graft DSA (g-DSA). Third, regarding organ transplantation between sensitized pairs, the acceptable outcomes are obtained owing to recent preoperative desensitization protocols: depletion/modification of B cells, apheresis for antibodies, and inhibition of reaction between DSA and HLA. Finally, we would like to discuss the treatment of AMR. Further advances in diagnosis methods and emergences of effective treatments would be expected for acceptable control of AMR. In this chapter, we will review from the basics to recent topics in order to understand DSA and AMR.

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Flow Cytometry and Solid Organ Transplantation: A Perfect Match

Cited by 26 publications

References 109 publications

Differential T Cell Signaling Pathway Activation by Tacrolimus and Belatacept after Kidney Transplantation: Post Hoc Analysis of a Randomised-Controlled Trial

Differential T Cell Signaling Pathway Activation by Tacrolimus and Belatacept after Kidney Transplantation: Post Hoc Analysis of a Randomised-Controlled Trial

Clinical significance of assessing the subpopulation composition of blood lymphocytes in patients with infectious corneal lesions in high-risk keratoplasty

Donor-Specific Anti-HLA Antibodies in Organ Transplantation: Transition from Serum DSA to Intra-Graft DSA

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