Ikaros expression is associated with an increased risk of chronic graft-versus-host disease

Abstract Immune reconstitution after hematopoietic stem cell transplantation (HSCT) is a complex and extremely variable process. The Ikaros transcription factor plays an important role in hematopoiesis in several cell lines, especially in the lymphoid lineage. We hypothesized that Ikaros might influ...

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Main Authors: A. D. Pereira, V. C. de Molla, A. R. B. M. Fonseca, L. Tucunduva, Y. Novis, M. S. Pires, A. F. Popi, C. A. Arrais-Rodrigues
Format: Article
Language:English
Published: Nature Portfolio 2023-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-35609-3
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author A. D. Pereira
V. C. de Molla
A. R. B. M. Fonseca
L. Tucunduva
Y. Novis
M. S. Pires
A. F. Popi
C. A. Arrais-Rodrigues
author_facet A. D. Pereira
V. C. de Molla
A. R. B. M. Fonseca
L. Tucunduva
Y. Novis
M. S. Pires
A. F. Popi
C. A. Arrais-Rodrigues
author_sort A. D. Pereira
collection DOAJ
description Abstract Immune reconstitution after hematopoietic stem cell transplantation (HSCT) is a complex and extremely variable process. The Ikaros transcription factor plays an important role in hematopoiesis in several cell lines, especially in the lymphoid lineage. We hypothesized that Ikaros might influence immune reconstitution, and consequently, the risk of opportunistic infections, relapse, and graft versus host disease (GVHD). Samples were collected from the graft and from the peripheral blood (PB) of the recipients 3 weeks after neutrophil recovery. Real-time polymerase chain reaction (RT-PCR) was performed to analyze the absolute and relative Ikaros expression. Patients were divided into two groups, according to Ikaros expression in the graft and in the recipients’ PB based on the ROC curves for moderate/severe cGVHD. A cutoff of 1.48 was used for Ikaros expression in the graft, and a cutoff of 0.79 was used for Ikaros expression in the recipients’ PB. Sixty-six patients were included in this study. Median age of patients was 52 years (range 16–80 years), 55% of them were male, and 58% of them had acute leukemia. Median follow-up period was 18 months (range 10–43 months). There was no association between Ikaros expression and the risk of acute GVHD, relapse, or mortality. However, a significant association was observed with the risk of chronic GVHD. Higher Ikaros expression in the graft was associated with a significantly higher cumulative incidence (CI) of moderate/severe chronic GVHD according to the National Institute of Health (NIH) classification at two years (54% vs. 15% for patients with lower expression, P = 0.03). A higher Ikaros expression in the recipients’ PB 3 weeks after engraftment was also associated with a significantly higher risk of moderate/severe chronic GVHD (65% vs. 11%, respectively, P = 0.005). In conclusion, Ikaros expression in the graft and in the recipients’ PB after transplantation was associated with a higher risk of moderate/severe chronic GVHD. Ikaros expression should be evaluated in larger prospective trials as a potential biomarker for chronic GVHD.
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spelling doaj.art-768223b413174339a6c7d4913ec5e5ce2023-05-28T11:13:41ZengNature PortfolioScientific Reports2045-23222023-05-011311710.1038/s41598-023-35609-3Ikaros expression is associated with an increased risk of chronic graft-versus-host diseaseA. D. Pereira0V. C. de Molla1A. R. B. M. Fonseca2L. Tucunduva3Y. Novis4M. S. Pires5A. F. Popi6C. A. Arrais-Rodrigues7Universidade Federal de São PauloUniversidade Federal de São PauloUniversidade Federal de São PauloCentro de Oncologia, Hospital Sírio LibanêsCentro de Oncologia, Hospital Sírio LibanêsUniversidade Federal de São PauloUniversidade Federal de São PauloUniversidade Federal de São PauloAbstract Immune reconstitution after hematopoietic stem cell transplantation (HSCT) is a complex and extremely variable process. The Ikaros transcription factor plays an important role in hematopoiesis in several cell lines, especially in the lymphoid lineage. We hypothesized that Ikaros might influence immune reconstitution, and consequently, the risk of opportunistic infections, relapse, and graft versus host disease (GVHD). Samples were collected from the graft and from the peripheral blood (PB) of the recipients 3 weeks after neutrophil recovery. Real-time polymerase chain reaction (RT-PCR) was performed to analyze the absolute and relative Ikaros expression. Patients were divided into two groups, according to Ikaros expression in the graft and in the recipients’ PB based on the ROC curves for moderate/severe cGVHD. A cutoff of 1.48 was used for Ikaros expression in the graft, and a cutoff of 0.79 was used for Ikaros expression in the recipients’ PB. Sixty-six patients were included in this study. Median age of patients was 52 years (range 16–80 years), 55% of them were male, and 58% of them had acute leukemia. Median follow-up period was 18 months (range 10–43 months). There was no association between Ikaros expression and the risk of acute GVHD, relapse, or mortality. However, a significant association was observed with the risk of chronic GVHD. Higher Ikaros expression in the graft was associated with a significantly higher cumulative incidence (CI) of moderate/severe chronic GVHD according to the National Institute of Health (NIH) classification at two years (54% vs. 15% for patients with lower expression, P = 0.03). A higher Ikaros expression in the recipients’ PB 3 weeks after engraftment was also associated with a significantly higher risk of moderate/severe chronic GVHD (65% vs. 11%, respectively, P = 0.005). In conclusion, Ikaros expression in the graft and in the recipients’ PB after transplantation was associated with a higher risk of moderate/severe chronic GVHD. Ikaros expression should be evaluated in larger prospective trials as a potential biomarker for chronic GVHD.https://doi.org/10.1038/s41598-023-35609-3
spellingShingle A. D. Pereira
V. C. de Molla
A. R. B. M. Fonseca
L. Tucunduva
Y. Novis
M. S. Pires
A. F. Popi
C. A. Arrais-Rodrigues
Ikaros expression is associated with an increased risk of chronic graft-versus-host disease
Scientific Reports
title Ikaros expression is associated with an increased risk of chronic graft-versus-host disease
title_full Ikaros expression is associated with an increased risk of chronic graft-versus-host disease
title_fullStr Ikaros expression is associated with an increased risk of chronic graft-versus-host disease
title_full_unstemmed Ikaros expression is associated with an increased risk of chronic graft-versus-host disease
title_short Ikaros expression is associated with an increased risk of chronic graft-versus-host disease
title_sort ikaros expression is associated with an increased risk of chronic graft versus host disease
url https://doi.org/10.1038/s41598-023-35609-3
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