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- Stikvoort, Arwen, et al.
(författare)
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Combining Flow and Mass Cytometry in the Search for Biomarkers in Chronic Graft-versus-Host Disease
- 2017
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Ingår i: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Chronic graft-versus-host disease (cGVHD) is a debilitating complication arising in around half of all patients treated with an allogeneic hematopoietic stem cell transplantation. Even though treatment of severe cGVHD has improved during recent years, it remains one of the main causes of morbidity and mortality in affected patients. Biomarkers in blood that could aid in the diagnosis and classification of cGVHD severity are needed for the development of novel treatment strategies that can alleviate symptoms and reduce the need for painful and sometimes complicated tissue biopsies. Methods that comprehensively profile complex biological systems such as the immune system can reveal unanticipated markers when used with the appropriate methods of data analysis. Here, we used mass cytometry, flow cytometry, enzyme-linked immunosorbent assay, and multiplex assays to systematically profile immune cell populations in 68 patients with varying grades of cGVHD. We identified multiple subpopulations across T, B, and NK-cell lineages that distinguished patients with cGVHD from those without cGVHD and which were associated in varying ways with severity of cGVHD. Specifically, initial flow cytometry demonstrated that patients with more severe cGVHD had lower mucosal-associated T cell frequencies, with a concomitant higher level of CD38 expression on T cells. Mass cytometry could identify unique subpopulations specific for cGVHD severity albeit with some seemingly conflicting results. For instance, patients with severe cGVHD had an increased frequency of activated B cells compared to patients with moderate cGVHD while activated B cells were found at a reduced frequency in patients with mild cGVHD compared to patients without cGVHD. Moreover, results indicate it may be possible to validate mass cytometry results with clinically viable, smaller flow cytometry panels. Finally, no differences in levels of blood soluble markers could be identified, with the exception for the semi-soluble combined marker B-cell activating factor/B cell ratio, which was increased in patients with mild cGVHD compared to patients without cGVHD. These findings suggest that interdependencies between such perturbed subpopulations of cells play a role in cGVHD pathogenesis and can serve as future diagnostic and therapeutic targets.
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- Stikvoort, Arwen, et al.
(författare)
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Risk Factors for Severe Acute Graft-versus-Host Disease in Donor Graft Composition
- 2018
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Ingår i: Biology of blood and marrow transplantation. - : ELSEVIER SCIENCE INC. - 1083-8791 .- 1523-6536. ; 24:3, s. 467-477
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Tidskriftsartikel (refereegranskat)abstract
- Acute graft-versus-host disease (aGVHD) is 1 of the main major complications of post-hematopoietic stem cell transplantation (HSCT). Identifying patients at risk of severe aGVHD may lead to earlier intervention and treatment, resulting in increased survival and a better quality of life. We aimed to identify biomarkers in donor grafts and patient plasma around the time of transplantation that might be predictive of aGVHD development. We build on our previously published methods by using multiplex assays and multicolor flow cytometry. We identified 5 easily assessable cellular markers in donor grafts that combined could potentially be used to calculate risk for severe aGVHD development. Most noteworthy are the T cell subsets expressing IL-7 receptor-a (CD127) and PD-1. Additionally, we identified a potential role for elevated tumor necrosis factor-a levels in both graft and patient before HSCT in development of aGVHD.
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