Plasmacytoid dendritic cells in allogeneic hematopoietic cell transplantation: benefit or burden?

Jj, Auletta; Devine, S M; Waller, Edmund K.

doi:10.1038/bmt.2015.301

Cited by 24 publications

(27 citation statements)

References 134 publications

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“…In patients with systemic lupus erythematosus, it has been previously shown that plasmacytoid dendritic cells drive the differentiation of immature regulatory B cells, and that these interactions are normalized in patients responding to rituximab therapy [38]. After HCT, the increase in plasmacytoid dendritic cells in bone marrow allografts is associated with less cGVHD [39], and rituximab has been successfully used as salvage therapy for steroid refractory cGVHD [40].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive B Cell Phenotyping Profile for Chronic Graft-versus-Host Disease Diagnosis

Rozmus

Kariminia

Abdossamadi

et al. 2019

Biology of Blood and Marrow Transplantation

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Previous studies have reported single B cell-related chronic graft-versus-host disease diagnostic (cGVHD) biomarkers, such as B cell-activating factor (BAFF), CD21 low , and immature B cells, but research on the performance of biomarker combinations and the covariate effect of steroids is lacking. The primary objective of this study was to determine the most accurate combination of B cell populations using cell surface staining flow cytometry in an independent cohort of patients with cGVHD. Secondary objectives included assessing the effect of corticosteroid use at sample collection on the makeup and accuracy of the diagnostic panel and identifying the mechanism underlying low surface expression of BAFF receptor (BAFF-R) on B cells in cGVHD. Flow cytometry analysis was performed in an adult cohort of post-HCT patients with cGVHD onset (n = 44) and time-matched recipients without cGVHD (n = 63). We confirmed that the onset of cGVHD was associated with higher soluble BAFF (sBAFF) levels, elevated CD27 ¡ CD10 ¡ CD21 low CD19 + B cell and classical switched memory B cell counts, and reduced transitional and na€ ıve B cell counts. The highest single B cell population area under the receiver operating characteristic (ROC) curve (AUC) was .72 for transitional type 1 CD21 low B cells. We also showed a significant inverse relationship between sBAFF and surface BAFF-R expression caused by sBAFF modulation of BAFF-R. Steroid use at sample collection influenced the significance of the sBAFF:B cell ratio, na€ ıve and marginal zone-like B cells. The optimal combination of B cell subsets most significantly associated with cGVHD onset with or without concurrent corticosteroid use resulted in ROC AUCs of .87 and .84, respectively. Transitional and CD21 low B cells were the only populations present in both panels; however, analyzing only these populations resulted in ROC AUCs of .79 and .78, respectively. This suggests that the inclusion of other populations and use of different panels depending on steroid use is necessary to achieve better accuracy. sBAFF was not a component of either panel. These novel B cell profiles could be tested prospectively in patients post-HSCT and could lead to focused mechanistic studies.

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Section: Discussionmentioning

confidence: 99%

Comprehensive B Cell Phenotyping Profile for Chronic Graft-versus-Host Disease Diagnosis

Rozmus

Kariminia

Abdossamadi

et al. 2019

Biology of Blood and Marrow Transplantation

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“…The possible role of pDCs in inducing aGVHD is interesting, but so far these cells have not been studied extensively in this context (26, 51). pDCs constitute a multifunctional cell type involved e.g., in production of type-I interferons against virus infections, induction of Th17 cell response, and presentation of peptide antigens by MHC class II to T cells (52).…”

Section: Discussionmentioning

confidence: 99%

“…Then, they may become activated and act as APC. However, experimental data for this is still scarce (51, 53). Peric et al recently reported that high levels of pDCs post-HSCT predicted good clinical outcome with less severe GVHD and better overall survival (53).…”

Section: Discussionmentioning

confidence: 99%

Graft Immune Cell Composition Associates with Clinical Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients with AML

et al. 2016

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Complications of allogeneic hematopoietic stem cell transplantation (HSCT) have been attributed to immune cells transferred into the patient with the graft. However, a detailed immune cell composition of the graft is usually not evaluated. In the present study, we determined the level of variation in the composition of immune cells between clinical HSCT grafts and whether this variation is associated with clinical outcome. Sizes of major immune cell populations in 50 clinical grafts from a single HSCT Centre were analyzed using flow cytometry. A statistical comparison between cell levels and clinical outcomes of HSCT was performed. Overall survival, acute graft-versus-host disease (aGVHD), chronic graft-versus-host disease (cGVHD), and relapse were used as the primary endpoints. Individual HSCT grafts showed considerable variation in their numbers of immune cell populations, including CD123+ dendritic cells and CD34+ cells, which may play a role in GVHD. Acute myeloid leukemia (AML) patients who developed aGVHD were transplanted with higher levels of effector CD3+ T, CD19+ B, and CD123+ dendritic cells than AML patients without aGVHD, whereas grafts with a high CD34+ content protected against aGVHD. AML patients with cGVHD had received grafts with a lower level of monocytes and a higher level of CD34+ cells than those without cGVHD. There is considerable variation in the levels of immune cell populations between HSCT grafts, and this variation is associated with outcomes of HSCT in AML patients. A detailed analysis of the immune cell content of the graft can be used in risk assessment of HSCT.

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“…Notably, in a phase I clinical trial, we recently demonstrated that 6 weeks course of subcutaneous injection of FLT3 ligand after autologous HCT increased the frequency of blood CD11c+ pDC precursors 5-fold without affecting other mature cell lineages [36]. Furthermore, high pDC can recruit NK and T cells to further promote local and systemic immune responses [37], yet our data did not confirm their correlation in peripheral blood.…”

Section: Discussionmentioning

confidence: 61%

Dendritic Cell Recovery Impacts Outcomes after Umbilical Cord Blood and Sibling Donor Transplantation for Hematologic Malignancies

Touma

Brunstein

Cao

et al. 2017

Biology of Blood and Marrow Transplantation

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Dendritic cells (DCs) orchestrate immune responses after allogeneic hematopoietic cell transplantation (HCT). We studied the association of donor myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) recovery in the landmark analysis of umbilical cord blood (UCB) and matched related donor (RD) HCT. Eighty patients (42 UCB and 38 RD recipients) with a day 100 (D+100) blood sample were included in the analysis. Median age was 51 years (20–71). Most patients had acute leukemia (50%) or lymphoma (23%) and received reduced-intensity conditioning (75%). UCB recipients had better mDC and pDC reconstitution compared to RD recipients reaching normal levels at D+100 post-transplant. Patients with high D+100 pDCs levels (≥ median 4.7 cells/µL) had 2-fold lower relapse compared to pDClow (<4.7 cells/µL; 14% vs. 28%; P=0.29) which was associated with improved 1-year survival for UCB recipients with D+100 pDChigh vs. pDClow (Overall survival: 100% vs. 81%; P=0.04; Progression free-survival: 86% vs. 62%; P=0.07). After RD HCT, mDC or pDC recovery at D+100 did not affect outcomes. In multivariate analysis, OS was improved with better pDC recovery (HR 0.18; 95%CI: 0.04–0.86; P=0.03). Collectively, this data suggests that UCB recipients with high levels of circulating pDCs at D+100 experience a survival advantage at 1 year.

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Plasmacytoid dendritic cells in allogeneic hematopoietic cell transplantation: benefit or burden?

Cited by 24 publications

References 134 publications

Comprehensive B Cell Phenotyping Profile for Chronic Graft-versus-Host Disease Diagnosis

Comprehensive B Cell Phenotyping Profile for Chronic Graft-versus-Host Disease Diagnosis

Graft Immune Cell Composition Associates with Clinical Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients with AML

Dendritic Cell Recovery Impacts Outcomes after Umbilical Cord Blood and Sibling Donor Transplantation for Hematologic Malignancies

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