scholarly journals Clinical Significance of Long Noncoding RNA-DC Expression in Acute Graft Versus Host Disease (AGVHD) Development

2020 ◽  
Vol 13 (9) ◽  
Author(s):  
Leila Jafari ◽  
Abbas Hajifathali ◽  
Mohammad Hossein Mohammadi ◽  
Hamid Ghaedi ◽  
Mehdi Allahbakhshian Farsiani ◽  
...  
Keyword(s):  
Immune Responses ◽  
T Cell Activation ◽  
Graft Versus Host Disease ◽  
Noncoding Rna ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

Background: Acute graft versus host disease (aGVHD) is a common complication following allogeneic hematopoietic stem cell transplantation (AHSCT) caused by cellular and inflammatory factors, including those arising from monocytes and dendritic cells as integral parts of the immune system. Long non-coding RNAs (lncRNA) have recently emerged as potential regulators of the immune responses and it is supported that their dysregulation can develop various immune disorders. As an intergenic lncRNA, the lnc-DC was shown to regulate the human monocytes differentiation and antigen presenting cells (APCs) activation during immune responses. It is also shown that lnc-DC knockdown reduces T-cell activation and cytokine release. Objectives: The aim of this study was to assess whether the lnc-DC plays a role in patients with aGVHD by measuring its expression levels compared to non-aGVHD patients on specific time intervals following transplantation. Methods: Participants included 38 patients who underwent primary allogeneic bone marrow transplantation. Peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll-Hypaque gradient from the blood samples collected at days 0, 7, 14, 28, and final day of transplantation. The qRT-PCR was used to quantify the lnc-DC levels. Results: Findings revealed a significant increase in the lnc-DC levels on day 28 and the final day after transplantation in patients with aGVHD compared to non-GVHD patients (CI = 95%, P < 0.03 on day 28 and P < 0.01 on the final day). Furthermore, the receiver operating characteristic (ROC) curve analysis showed an acceptable total area under the curve for the lnc-DC gene expression data, suggesting a fair diagnostic value for lnc-DC. Conclusions: Taken together, data of the present study supported a strong correlation between lncRNA-DC expression and aGVHD occurrence. As a result, lnc-DC may be considered as a new molecular marker for the aGVHD prognosis.

The primacy of the gastrointestinal tract as a target organ of acute graft-versus-host disease: rationale for the use of cytokine shields in allogeneic bone marrow transplantation

Blood ◽  
2000 ◽  
Vol 95 (9) ◽  
pp. 2754-2759 ◽  
Author(s):  
Geoffrey R. Hill ◽  
James L. M. Ferrara
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone ◽  
Gi Tract ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

Acute graft-versus-host disease (GVHD), the major complication of allogeneic bone marrow transplantation (BMT), limits the application of this curative but toxic therapy. Studies of inflammatory pathways involved in GVHD in animals have shown that the gastrointestinal (GI) tract plays a major role in the amplification of systemic disease. Damage to the GI tract increases the translocation of inflammatory stimuli such as endotoxin, which promotes further inflammation and additional GI tract damage. The GI tract is therefore critical to the propagation of the “cytokine storm” characteristic of acute GVHD. Experimental approaches to the prevention of GVHD include reducing the damage to the GI tract by fortification of the GI mucosal barrier through novel “cytokine shields” such as IL-11 or keratinocyte growth factor. Such strategies have reduced GVHD while preserving a graft-versus-leukemia effect in animal models, and they now deserve formal testing in carefully designed clinical trials.

scholarly journals The Role of Intestinal Microbiota in Acute Graft-versus-Host Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Yuanyuan Chen ◽  
Ye Zhao ◽  
Qiao Cheng ◽  
Depei Wu ◽  
Haiyan Liu
Keyword(s):  
Immune Responses ◽  
Intestinal Microbiota ◽  
Graft Versus Host Disease ◽  
Inflammatory Diseases ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Host Immune Responses ◽  
Acute Graft

The mammalian intestinal microbiota is a complex ecosystem that plays an important role in host immune responses. Recent studies have demonstrated that alterations in intestinal microbiota composition are linked to multiple inflammatory diseases in humans, including acute graft-versus-host disease (aGVHD). aGVHD is one of the major obstacles in allogeneic hematopoietic stem cell transplantation (allo-HSCT), characterized by tissue damage in the gastrointestinal (GI) tract, liver, lung, and skin. Here, we review the current understanding of the role of intestinal microbiota in the control of immune responses during aGVHD. Additionally, the possibility of using probiotic strains for potential treatment or prevention of aGVHD will be discussed.

Tryptophan Metabolites Analogue, N-(3,4-dimethoxycinnamonyl) Anthranilic Acid, Ameliorates Acute Graft-Versus-Host Disease Through Inhibiting Th1 Responses

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5421-5421
Author(s):  
Jinhuan Xu ◽  
Yicheng Zhang
Keyword(s):  
T Lymphocytes ◽  
Graft Versus Host Disease ◽  
Anthranilic Acid ◽  
Allogeneic Bone Marrow Transplantation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Allogeneic Bone ◽  
Host Disease ◽  
Graft Versus Host ◽  
Ifn Γ ◽  
Acute Graft

Abstract Local catabolism of tryptophan (Trp) by indoleamine 2,3-dioxygenase (IDO) is considered an important mechanism of regulating T cell immunity. N-(3,4-dimethoxycinnamonyl) anthranilic acid (3,4-DAA) is an active synthetic anthranilic acid derivative which was proved to be effective to treat type±helper T lymphocytes (Th1) mediated autoimmune diseases such as multiple sclerosis. In this report, we investigated the effects of 3,4-DAA on the acute graft versus host disease (aGVHD) following allogeneic bone marrow transplantation (allo-BMT) and its potential mechanism of action. we established a murine aGVHD model, 3,4-DAA was injected intraperitoneally at 200 mg/kg/day per mouse immediately after allo-BMT or at the onset of aGVHD for 14 consecutive days; the signs of aGVHD and the survival were recorded periodically; the histological changes of target organs were evaluated with hematoxylin-eosin staining; the IDO activity and cytokine levels in plasma were measured by reverse-phase high-performance liquid chromatography (HPLC) and enzyme linked immunosorbent assay (ELISA), respectively. We revealed that administration of 3,4-DAA after allo-BMT significantly reduced the severity and the histological score of aGVHD; The survival for mice receiving 3,4-DAA prophylaxis and treatment were prolonged in comparison to the vehicle control mice. The plasma levels of IFN-γ, TNF-α, IL-12 and IL-2 in 3,4-DAA treatment group were found to be decreased, while the IDO activity, the IL-10, IL-5 and IL-4 levels elevated in these mice. In consistent with the in vivo results, 3,4-DAA also inhibited IFN-γ and IL-2 production of spleen T lymphocytes in vitro. Our findings suggest that 3,4-DAA can diminish the murine experimental aGVHD through inhibition of Th1 response; this property makes it a potential alternative agent for prevention and treatment of GVHD in the clinic. Disclosures: No relevant conflicts of interest to declare.

Pentostatin in Steroid-Refractory Acute Graft-Versus-Host Disease

2005 ◽  
Vol 23 (12) ◽  
pp. 2661-2668 ◽  
Author(s):  
Javier Bolaños-Meade ◽  
David A. Jacobsohn ◽  
Jeffrey Margolis ◽  
Adam Ogden ◽  
M. Guillaume Wientjes ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Allogeneic Bone Marrow Transplantation ◽  
Major Complication ◽  
Maximum Tolerated Dose ◽  
Allogeneic Bone ◽  
Dose Escalation Study ◽  
Host Disease ◽  
Graft Versus Host ◽  
Steroid Refractory ◽  
Acute Graft

Purpose Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic bone marrow transplantation. In steroid-refractory aGVHD, mortality is very high. Pentostatin, a potent inhibitor of adenosine deaminase, induces lymphocyte apoptosis and may be useful in the treatment of this condition. Patients and Methods We have conducted a phase I dose escalation study of pentostatin in patients with steroid-refractory aGVHD. Twenty-three patients were enrolled. Starting dose was 1 mg/m2/d by intravenous injection for 3 days. Results The maximum tolerated dose was found to be 1.5 mg/m2/d. Late infections at the 2-mg/m2/d dose level were believed to be dose limiting toxicities. Lymphopenia was universal, but the neutrophil count was generally not affected. Fevers associated with neutropenia were not observed. Otherwise, the drug was well tolerated, with only modest elevations of liver function tests and thrombocytopenia, each being observed in a single patient. Twenty-two patients were assessable for response, including 14 complete responses (63%) and three partial responses (13%). Median survival after therapy for the group was 85 days (range, 5 to 1,258 days). Conclusion The suggested intravenous dose for a phase II study will be 1.5 mg/m2/d for 3 days. Pentostatin has activity in patients with steroid-refractory aGVHD that is worth exploring in future trials.

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