High Frequency of Post-Transfusion Microchimerism Among Multi-Transfused Beta-Thalassemic Patients

BackgroundTransfusion-associated microchimerism implies the presence of allogeneic hematopoietic cells in an individual, following the transfusion of a blood product. It is a transfusion-related adverse effect/long-term consequence, which has not been well-investigated among regularly transfused pat...

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Main Authors: Spyridon Matsagos, Evgenia Verigou, Alexandra Kourakli, Spyridon Alexis, Spyridon Vrakas, Constantina Argyropoulou, Vasileios Lazaris, Panagiota Spyropoulou, Vasiliki Labropoulou, Nicoletta Georgara, Maria Lykouresi, Marina Karakantza, Chrysoula Alepi, Argiris Symeonidis
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-02-01
Series:Frontiers in Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2022.845490/full
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author Spyridon Matsagos
Spyridon Matsagos
Evgenia Verigou
Alexandra Kourakli
Spyridon Alexis
Spyridon Vrakas
Constantina Argyropoulou
Vasileios Lazaris
Panagiota Spyropoulou
Vasiliki Labropoulou
Nicoletta Georgara
Maria Lykouresi
Marina Karakantza
Chrysoula Alepi
Argiris Symeonidis
author_facet Spyridon Matsagos
Spyridon Matsagos
Evgenia Verigou
Alexandra Kourakli
Spyridon Alexis
Spyridon Vrakas
Constantina Argyropoulou
Vasileios Lazaris
Panagiota Spyropoulou
Vasiliki Labropoulou
Nicoletta Georgara
Maria Lykouresi
Marina Karakantza
Chrysoula Alepi
Argiris Symeonidis
author_sort Spyridon Matsagos
collection DOAJ
description BackgroundTransfusion-associated microchimerism implies the presence of allogeneic hematopoietic cells in an individual, following the transfusion of a blood product. It is a transfusion-related adverse effect/long-term consequence, which has not been well-investigated among regularly transfused patients with thalassemia.Patients and MethodsWe investigated 64 regularly transfused, homozygous β-thalassemic patients and 21 never-transfused healthy volunteer blood donors (controls) for the presence of microchimerism in their sera, using real-time PCR targeting circulating allogeneic, both, Human Leukocyte Antigen-DR isotype (HLA-DR) and non-HLA alleles. The investigation was longitudinally repeated in patient subsets for more than 2 years. Results were correlated with clinical and laboratory parameters, peripheral blood lymphocyte immunophenotype, blood storage time, and donor's gender to identify potential contributing factors for microchimerism generation.ResultsOverall, microchimerism was detected in 52 of the 64 patients (81.2%) and in 6 of the 21 controls (28.5%, p = 0.0001). Forty-four patients (68.7%) exhibited long-term microchimerism (persisted for more than 6 months), confirmed at all time-points investigated. Microchimerism was more frequent among elderly, women, splenectomized and more heavily transfused patients, and among those who exhibit higher serum ferritin levels. In these patients, a distinct descending pattern of CD16dim+CD56dim+ natural killer (NK)-cells (p < 0.001) and an ascending pattern of CD4+CD25brightCD127– regulatory T-cells (p = 0.022) for increasing allelic burden were noticed, suggesting the establishment of recipient immune tolerance against the donor-derived chimeric alleles. Both splenectomized and non-splenectomized thalassemic patients exhibited the same trend. The storage time of transfused blood products and donor/gender mismatch had no impact on the development of microchimerism.Discussion-Conclusive RemarksTransfusion-associated microchimerism appears to be a very common complication among multi-transfused thalassemic patients. The potential clinical consequences of this phenomenon remain as yet unclear. Immune tolerance attributed to disease itself and to repeated transfusions might at least in part explain its appearance.
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spelling doaj.art-9ebf14b321404922b7f784f32383f1192022-12-21T21:40:21ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-02-01910.3389/fmed.2022.845490845490High Frequency of Post-Transfusion Microchimerism Among Multi-Transfused Beta-Thalassemic PatientsSpyridon Matsagos0Spyridon Matsagos1Evgenia Verigou2Alexandra Kourakli3Spyridon Alexis4Spyridon Vrakas5Constantina Argyropoulou6Vasileios Lazaris7Panagiota Spyropoulou8Vasiliki Labropoulou9Nicoletta Georgara10Maria Lykouresi11Marina Karakantza12Chrysoula Alepi13Argiris Symeonidis14Department of Transfusion Medicine and Blood Bank, “Tzaneion” General Hospital, Piraeus, GreeceHematology Division, Department of Internal Medicine, University of Patras Medical School, Patras, GreeceHematology Division, Department of Internal Medicine, University of Patras Medical School, Patras, GreeceHematology Division, Department of Internal Medicine, University of Patras Medical School, Patras, GreeceHematology Division, Department of Internal Medicine, University of Patras Medical School, Patras, GreeceGastroenterology Department, “Tzaneion” General Hospital, Piraeus, GreeceHematology Division, Department of Internal Medicine, University of Patras Medical School, Patras, GreeceHematology Division, Department of Internal Medicine, University of Patras Medical School, Patras, GreeceDepartment of Transfusion Medicine and Blood Bank, “Tzaneion” General Hospital, Piraeus, GreeceHematology Division, Department of Internal Medicine, University of Patras Medical School, Patras, GreeceDepartment of Transfusion Medicine and Blood Bank, University Regional General Hospital of Patras, Patras, GreeceDepartment of Transfusion Medicine and Blood Bank, “Tzaneion” General Hospital, Piraeus, GreeceHaematology and Transfusion Department, National Health Service Blood and Transplant, Leeds Teaching, Hospital Trust, Leeds, United KingdomDepartment of Transfusion Medicine and Blood Bank, “Tzaneion” General Hospital, Piraeus, GreeceHematology Division, Department of Internal Medicine, University of Patras Medical School, Patras, GreeceBackgroundTransfusion-associated microchimerism implies the presence of allogeneic hematopoietic cells in an individual, following the transfusion of a blood product. It is a transfusion-related adverse effect/long-term consequence, which has not been well-investigated among regularly transfused patients with thalassemia.Patients and MethodsWe investigated 64 regularly transfused, homozygous β-thalassemic patients and 21 never-transfused healthy volunteer blood donors (controls) for the presence of microchimerism in their sera, using real-time PCR targeting circulating allogeneic, both, Human Leukocyte Antigen-DR isotype (HLA-DR) and non-HLA alleles. The investigation was longitudinally repeated in patient subsets for more than 2 years. Results were correlated with clinical and laboratory parameters, peripheral blood lymphocyte immunophenotype, blood storage time, and donor's gender to identify potential contributing factors for microchimerism generation.ResultsOverall, microchimerism was detected in 52 of the 64 patients (81.2%) and in 6 of the 21 controls (28.5%, p = 0.0001). Forty-four patients (68.7%) exhibited long-term microchimerism (persisted for more than 6 months), confirmed at all time-points investigated. Microchimerism was more frequent among elderly, women, splenectomized and more heavily transfused patients, and among those who exhibit higher serum ferritin levels. In these patients, a distinct descending pattern of CD16dim+CD56dim+ natural killer (NK)-cells (p < 0.001) and an ascending pattern of CD4+CD25brightCD127– regulatory T-cells (p = 0.022) for increasing allelic burden were noticed, suggesting the establishment of recipient immune tolerance against the donor-derived chimeric alleles. Both splenectomized and non-splenectomized thalassemic patients exhibited the same trend. The storage time of transfused blood products and donor/gender mismatch had no impact on the development of microchimerism.Discussion-Conclusive RemarksTransfusion-associated microchimerism appears to be a very common complication among multi-transfused thalassemic patients. The potential clinical consequences of this phenomenon remain as yet unclear. Immune tolerance attributed to disease itself and to repeated transfusions might at least in part explain its appearance.https://www.frontiersin.org/articles/10.3389/fmed.2022.845490/fullthalassemiatransfusionadverse effectsmicrochimerismimmunomodulation
spellingShingle Spyridon Matsagos
Spyridon Matsagos
Evgenia Verigou
Alexandra Kourakli
Spyridon Alexis
Spyridon Vrakas
Constantina Argyropoulou
Vasileios Lazaris
Panagiota Spyropoulou
Vasiliki Labropoulou
Nicoletta Georgara
Maria Lykouresi
Marina Karakantza
Chrysoula Alepi
Argiris Symeonidis
High Frequency of Post-Transfusion Microchimerism Among Multi-Transfused Beta-Thalassemic Patients
Frontiers in Medicine
thalassemia
transfusion
adverse effects
microchimerism
immunomodulation
title High Frequency of Post-Transfusion Microchimerism Among Multi-Transfused Beta-Thalassemic Patients
title_full High Frequency of Post-Transfusion Microchimerism Among Multi-Transfused Beta-Thalassemic Patients
title_fullStr High Frequency of Post-Transfusion Microchimerism Among Multi-Transfused Beta-Thalassemic Patients
title_full_unstemmed High Frequency of Post-Transfusion Microchimerism Among Multi-Transfused Beta-Thalassemic Patients
title_short High Frequency of Post-Transfusion Microchimerism Among Multi-Transfused Beta-Thalassemic Patients
title_sort high frequency of post transfusion microchimerism among multi transfused beta thalassemic patients
topic thalassemia
transfusion
adverse effects
microchimerism
immunomodulation
url https://www.frontiersin.org/articles/10.3389/fmed.2022.845490/full
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