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CEACAM-1 Induced CSF3-receptor Downregulation in Bone Marrow Associated With Refractory Neutropenia in Advanced Cirrhosis
BACKGROUND AND AIMS: Cirrhosis patients exhibit cytopenia, and, at times refractory neutropenia to granulocyte colony-stimulating factor (G-CSF), which acts through the CSF3-receptor (CSF3R), and changes in CSF3R can affect the response. We conducted this study to assess the CSF3R status and its rel...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
XIA & HE Publishing Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8845158/ https://www.ncbi.nlm.nih.gov/pubmed/35233373 http://dx.doi.org/10.14218/JCTH.2021.00331 |
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author | Bihari, Chhagan Baweja, Sukriti Shasthry, Seggere Murlaikrishna Lal, Deepika Negi, Preeti Thangariyal, Swati Tripathi, Dinesh Mani Sarin, Shiv Kumar |
author_facet | Bihari, Chhagan Baweja, Sukriti Shasthry, Seggere Murlaikrishna Lal, Deepika Negi, Preeti Thangariyal, Swati Tripathi, Dinesh Mani Sarin, Shiv Kumar |
author_sort | Bihari, Chhagan |
collection | PubMed |
description | BACKGROUND AND AIMS: Cirrhosis patients exhibit cytopenia, and, at times refractory neutropenia to granulocyte colony-stimulating factor (G-CSF), which acts through the CSF3-receptor (CSF3R), and changes in CSF3R can affect the response. We conducted this study to assess the CSF3R status and its relevance in cirrhotic patients. METHODS: Cirrhotic patients (n=127) and controls (n=26) with clinically indicated bone marrow (BM) examination were studied. BM assessment was done by qRT-PCR and immunohistochemistry (IHC) for CSF3R. Circulating G-CSF, CSF3R, and carcinoembryonic antigen cell adhesion molecule-1 (CEACAM1) were measured. BM hematopoietic precursor cells and their alterations were examined by flow cytometry. The findings were validated in liver cirrhosis patients who received G-CSF for severe neutropenia. RESULTS: The mean age was 48.6±13.4 years, and 80.3% were men. Circulatory CSF3R reduction was noted with the advancement of cirrhosis, and confirmed by qRT-PCR and IHC in BM. CSF3R decline was related to decreased hematopoietic stem cells (HSCs) and downregulation of CSF3R in the remaining HSCs. Cocultures confirmed that CEACAM1 led to CSF3R downregulation in BM cells by possible lysosomal degradation. Baseline low peripheral blood-(PB)-CSF3R also predisposed development of infections on follow-up. Decreased CSF3R was also associated with nonresponse to exogenous G-CSF treatment of neutropenia. CONCLUSIONS: Advanced liver cirrhosis was associated with low CSF3R and high CEACAM1 levels in the BM and circulation, making patients prone to infection and inadequate response to exogenous G-CSF. |
format | Online Article Text |
id | pubmed-8845158 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | XIA & HE Publishing Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88451582022-02-28 CEACAM-1 Induced CSF3-receptor Downregulation in Bone Marrow Associated With Refractory Neutropenia in Advanced Cirrhosis Bihari, Chhagan Baweja, Sukriti Shasthry, Seggere Murlaikrishna Lal, Deepika Negi, Preeti Thangariyal, Swati Tripathi, Dinesh Mani Sarin, Shiv Kumar J Clin Transl Hepatol Original Article BACKGROUND AND AIMS: Cirrhosis patients exhibit cytopenia, and, at times refractory neutropenia to granulocyte colony-stimulating factor (G-CSF), which acts through the CSF3-receptor (CSF3R), and changes in CSF3R can affect the response. We conducted this study to assess the CSF3R status and its relevance in cirrhotic patients. METHODS: Cirrhotic patients (n=127) and controls (n=26) with clinically indicated bone marrow (BM) examination were studied. BM assessment was done by qRT-PCR and immunohistochemistry (IHC) for CSF3R. Circulating G-CSF, CSF3R, and carcinoembryonic antigen cell adhesion molecule-1 (CEACAM1) were measured. BM hematopoietic precursor cells and their alterations were examined by flow cytometry. The findings were validated in liver cirrhosis patients who received G-CSF for severe neutropenia. RESULTS: The mean age was 48.6±13.4 years, and 80.3% were men. Circulatory CSF3R reduction was noted with the advancement of cirrhosis, and confirmed by qRT-PCR and IHC in BM. CSF3R decline was related to decreased hematopoietic stem cells (HSCs) and downregulation of CSF3R in the remaining HSCs. Cocultures confirmed that CEACAM1 led to CSF3R downregulation in BM cells by possible lysosomal degradation. Baseline low peripheral blood-(PB)-CSF3R also predisposed development of infections on follow-up. Decreased CSF3R was also associated with nonresponse to exogenous G-CSF treatment of neutropenia. CONCLUSIONS: Advanced liver cirrhosis was associated with low CSF3R and high CEACAM1 levels in the BM and circulation, making patients prone to infection and inadequate response to exogenous G-CSF. XIA & HE Publishing Inc. 2022-02-28 2022-01-04 /pmc/articles/PMC8845158/ /pubmed/35233373 http://dx.doi.org/10.14218/JCTH.2021.00331 Text en © 2022 Authors. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 4.0 International License (CC BY-NC 4.0), permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Bihari, Chhagan Baweja, Sukriti Shasthry, Seggere Murlaikrishna Lal, Deepika Negi, Preeti Thangariyal, Swati Tripathi, Dinesh Mani Sarin, Shiv Kumar CEACAM-1 Induced CSF3-receptor Downregulation in Bone Marrow Associated With Refractory Neutropenia in Advanced Cirrhosis |
title | CEACAM-1 Induced CSF3-receptor Downregulation in Bone Marrow Associated With Refractory Neutropenia in Advanced Cirrhosis |
title_full | CEACAM-1 Induced CSF3-receptor Downregulation in Bone Marrow Associated With Refractory Neutropenia in Advanced Cirrhosis |
title_fullStr | CEACAM-1 Induced CSF3-receptor Downregulation in Bone Marrow Associated With Refractory Neutropenia in Advanced Cirrhosis |
title_full_unstemmed | CEACAM-1 Induced CSF3-receptor Downregulation in Bone Marrow Associated With Refractory Neutropenia in Advanced Cirrhosis |
title_short | CEACAM-1 Induced CSF3-receptor Downregulation in Bone Marrow Associated With Refractory Neutropenia in Advanced Cirrhosis |
title_sort | ceacam-1 induced csf3-receptor downregulation in bone marrow associated with refractory neutropenia in advanced cirrhosis |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8845158/ https://www.ncbi.nlm.nih.gov/pubmed/35233373 http://dx.doi.org/10.14218/JCTH.2021.00331 |
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