Immune activation- and regulation-related patterns in stable hand transplant recipients

Kamińska, Dorota; Kościelska‐Kasprzak, Katarzyna; Krajewska, Magdalena; Chełmoński, Adam; Jabłecki, Jerzy; Żabińska, Marcelina; Márta, Mészáros; Banasik, Mirosław; Boratyńska, Maria; Gomółkiewicz, Agnieszka; Dzięgiel, Piotr; Klinger, Marian

doi:10.1111/tri.12883

Cited by 5 publications

(5 citation statements)

References 49 publications

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“…We have previously reported that stable hand transplant recipients exhibit persistent immune activation with rejection-related gene expression pattern [42]. Our present study showed that in hand transplant recipients no higher levels of serum inflammatory markers (IFN-γ, IL-I, and IL-6) were observed.…”

Section: Discussionsupporting

confidence: 47%

Non-HLA Antibodies in Hand Transplant Recipients Are Connected to Multiple Acute Rejection Episodes and Endothelial Activation

Sikorska

Kamińska

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et al. 2022

JCM

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The role of anti-HLA antibodies in transplant rejection is well-known but the injury associated with non-HLA antibodies is now widely discussed. The aim of our study was to investigate a role of non-HLA antibodies in hand allografts rejection. The study was performed on six patients after hand transplantation. The control group consisted of: 12 kidney transplant recipients and 12 healthy volunteers. The following non-HLA antibodies were tested: antibody against angiotensin II type 1 receptor (AT1R-Ab), antibody against endothelin-1 type-A-receptor (ETAR-Ab), antibody against protease-activated receptor 1 (PAR-1-Ab) and anti-VEGF-A antibody (VEGF-A-Ab). Chosen proinflammatory cytokines (Il-1, IL-6, IFNγ) were used to evaluate the post-transplant humoral response. Laboratory markers of endothelial activation (VEGF, sICAM, vWF) were used to assess potential vasculopathy. The patient with the highest number of acute rejections had both positive non-HLA antibodies: AT1R-Ab and ETAR-Ab. The same patient had the highest VEGF-A-Ab and very high PAR1-Ab. All patients after hand transplantation had high levels of laboratory markers of endothelial activation. The existence of non-HLA antibodies together with multiple acute rejections observed in patient after hand transplantation should stimulate to look for potential role of non-HLA antibodies in humoral injury in vascular composite allotransplantation.

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Section: Discussionsupporting

confidence: 47%

Non-HLA Antibodies in Hand Transplant Recipients Are Connected to Multiple Acute Rejection Episodes and Endothelial Activation

Sikorska

Kamińska

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et al. 2022

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“…San Segundo et al [23] observed low levels of Tregs after KTx for six months after transplantation and their recovery to almost basal levels during the first posttransplant year, which may be explained by the high burden of immunosuppression in the early posttransplant period. On the contrary, we previously showed that stable kidney transplant recipients chronically presented lower counts of Tregs compared to controls and stable hand transplant recipients despite their higher immunosuppression load [24]. Moreover, long-term treatment with calcineurin inhibitors in contrast to mTOR inhibitors in stable human renal transplantation was linked to decreased Treg counts [25].…”

Section: Discussionmentioning

confidence: 99%

Kidney Transplant Outcome Is Associated with Regulatory T Cell Population and Gene Expression Early after Transplantation

Krajewska

Kościelska‐Kasprzak

Kamińska

et al. 2019

Journal of Immunology Research

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Successful long-term kidney allograft survival with parallel reduction of complications resulting from prolonged immunosuppressive treatment is a goal in kidney transplantation. We studied the immune changes in cell phenotypes and gene expression induced by kidney transplantation. Our goal was to find a phenotypic and/or transcriptional pattern that might be considered prognostic for the kidney transplant outcome. The analysis was performed prospectively on 36 KTx recipients sampled during the first year and followed for five years after transplantation and on 40 long-term KTx recipients (7.9 ± 2.2 y. post-KTx). The research involved flow cytometry assessment of lymphocyte subpopulations (including Tregs and CD3+CD8+CD28− lymphocytes) and gene expression analysis of immune-related genes (CD4, CD8, CTLA4, GZMB, FOXP3, IL10, IL4, ILR2A, NOTCH, PDCD1, PRF1, TGFB, and TNFA). The analysis of patterns observed over the first post-KTx year was confronted with control, pretransplant, and long-term transplant results. Treg counts at months one and three post-KTx correlated positively with the current and future allograft function. FOXP3 gene expression at month one post-KTx was also associated with long-term allograft function. The KTx-induced CD3+CD8+CD28− population correlated with GZMB and PRF1 expression and suggested their cytotoxic properties. The size of the Treg population and regulatory FOXP3 gene expression in the early period after transplantation are associated with kidney transplant outcome. The outlined predictive power of the Treg population needs to be investigated further to be confirmed as one of the immune monitoring strategies that may help achieve the best long-term kidney allograft outcomes.

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“…In this latter study, RT patients without a history of cancer post-transplant had similar numbers of Treg to HV, whereas patients with cancer post-transplant had increased CD4 + CD25 + Foxp3 + Treg. A comparison of 30 stable RT patients (mean 8 years post-transplant), 5 hand transplant patients (mean 5 years post-transplant) and 18 HV found that RT patients had fewer CD4 + CD25 + CD127 lo compared to the other groups ( 168 ).…”

Section: Changes In Treg Over Time In Renal Transplant Patientsmentioning

confidence: 99%

“…CD4 + CD25 hi CD127 lo T cells are highly suppressive in vitro ( 166 , 167 ). The CD4 + CD25 hi CD127 lo cells are a functional Treg population in renal transplant patients ( 119 , 126 , 132 , 137 , 154 , 168 , 169 ).…”

Section: Identification Of Treg Population In Peripheral Bloodmentioning

confidence: 99%

CD4+CD25+ T regulatory cells in renal transplantation

et al. 2022

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The immune response to an allograft activates lymphocytes with the capacity to cause rejection. Activation of CD4+CD25+Foxp3+T regulatory cells (Treg) can down-regulate allograft rejection and can induce immune tolerance to the allograft. Treg represent <10% of peripheral CD4+T cells and do not markedly increase in tolerant hosts. CD4+CD25+Foxp3+T cells include both resting and activated Treg that can be distinguished by several markers, many of which are also expressed by effector T cells. More detailed characterization of Treg to identify increased activated antigen-specific Treg may allow reduction of non-specific immunosuppression. Natural thymus derived resting Treg (tTreg) are CD4+CD25+Foxp3+T cells and only partially inhibit alloantigen presenting cell activation of effector cells. Cytokines produced by activated effector cells activate these tTreg to more potent alloantigen-activated Treg that may promote a state of operational tolerance. Activated Treg can be distinguished by several molecules they are induced to express, or whose expression they have suppressed. These include CD45RA/RO, cytokine receptors, chemokine receptors that alter pathways of migration and transcription factors, cytokines and suppression mediating molecules. As the total Treg population does not increase in operational tolerance, it is the activated Treg which may be the most informative to monitor. Here we review the methods used to monitor peripheral Treg, the effect of immunosuppressive regimens on Treg, and correlations with clinical outcomes such as graft survival and rejection. Experimental therapies involving ex vivo Treg expansion and administration in renal transplantation are not reviewed.

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Immune activation- and regulation-related patterns in stable hand transplant recipients

Cited by 5 publications

References 49 publications

Non-HLA Antibodies in Hand Transplant Recipients Are Connected to Multiple Acute Rejection Episodes and Endothelial Activation

Non-HLA Antibodies in Hand Transplant Recipients Are Connected to Multiple Acute Rejection Episodes and Endothelial Activation

Kidney Transplant Outcome Is Associated with Regulatory T Cell Population and Gene Expression Early after Transplantation

CD4+CD25+ T regulatory cells in renal transplantation

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