scholarly journals Low Paneth cell numbers at onset of gastrointestinal graft-versus-host disease identify patients at high risk for nonrelapse mortality

Blood ◽  
2013 ◽  
Vol 122 (8) ◽  
pp. 1505-1509 ◽  
Author(s):  
John E. Levine ◽  
Elisabeth Huber ◽  
Suntrea T. G. Hammer ◽  
Andrew C. Harris ◽  
Joel K. Greenson ◽  
...  
Keyword(s):  
High Risk ◽  
Light Microscopy ◽  
Graft Versus Host Disease ◽  
Paneth Cell ◽  
Paneth Cells ◽  
Host Disease ◽  
Graft Versus Host ◽  
Cell Numbers ◽  
Key Points ◽  
Histopathological Grading

Key Points Paneth cell numbers in the duodenum at onset of GVHD correlate with outcomes. Paneth cells are easy to identify and quantify with light microscopy and may supplement histopathological grading of GI GVHD.

scholarly journals Increased Mac-2 binding protein glycan isomer in patients at risk for late nonrelapse mortality after HSCT

2019 ◽  
Vol 3 (21) ◽  
pp. 3287-3296
Author(s):  
Yu Akahoshi ◽  
Hideki Nakasone ◽  
Koji Kawamura ◽  
Machiko Kusuda ◽  
Shunto Kawamura ◽  
...  
Keyword(s):  
At Risk ◽  
High Risk ◽  
Graft Versus Host Disease ◽  
Binding Protein ◽  
Liver Graft ◽  
Host Disease ◽  
Allogeneic Hsct ◽  
Graft Versus Host ◽  
Key Points ◽  
Patients At Risk

Key Points M2BPGi is increased in patients with liver graft-versus-host disease, especially in those at high risk for late NRM after allogeneic HSCT. WFA+-M2BP–positive macrophages are found in liver graft-versus-host disease, supporting these cells as a responder of this glycoprotein.

Graft-versus-host disease disrupts intestinal microbial ecology by inhibiting Paneth cell production of α-defensins

Blood ◽  
2012 ◽  
Vol 120 (1) ◽  
pp. 223-231 ◽  
Author(s):  
Yoshihiro Eriguchi ◽  
Shuichiro Takashima ◽  
Hideyo Oka ◽  
Sonoko Shimoji ◽  
Kiminori Nakamura ◽  
...  
Keyword(s):  
Microbial Communities ◽  
Graft Versus Host Disease ◽  
Paneth Cell ◽  
Polymyxin B ◽  
Paneth Cells ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Curative Therapy ◽  
Graft Versus Host ◽  
Close Relationship

AbstractAllogeneic hematopoietic stem cell transplantation (SCT) is a curative therapy for various hematologic disorders. Graft-versus-host disease (GVHD) and infections are the major complications of SCT, and their close relationship has been suggested. In this study, we evaluated a link between 2 complications in mouse models. The intestinal microbial communities are actively regulated by Paneth cells through their secretion of antimicrobial peptides, α-defensins. We discovered that Paneth cells are targeted by GVHD, resulting in marked reduction in the expression of α-defensins, which selectively kill noncommensals, while preserving commensals. Molecular profiling of intestinal microbial communities showed loss of physiologic diversity among the microflora and the overwhelming expansion of otherwise rare bacteria Escherichia coli, which caused septicemia. These changes occurred only in mice with GVHD, independently on conditioning-induced intestinal injury, and there was a significant correlation between alteration in the intestinal microbiota and GVHD severity. Oral administration of polymyxin B inhibited outgrowth of E coli and ameliorated GVHD. These results reveal the novel mechanism responsible for shift in the gut flora from commensals toward the widespread prevalence of pathogens and the previously unrecognized association between GVHD and infection after allogeneic SCT.

scholarly journals R-Spondin1 expands Paneth cells and prevents dysbiosis induced by graft-versus-host disease

2017 ◽  
Vol 214 (12) ◽  
pp. 3507-3518 ◽  
Author(s):  
Eiko Hayase ◽  
Daigo Hashimoto ◽  
Kiminori Nakamura ◽  
Clara Noizat ◽  
Reiki Ogasawara ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Fecal Microbiota Transplantation ◽  
Paneth Cell ◽  
Fecal Microbiota ◽  
Paneth Cells ◽  
Host Disease ◽  
Graft Versus Host ◽  
Cell Functions ◽  
Therapeutic Benefits ◽  
Physiological Approach

The intestinal microbial ecosystem is actively regulated by Paneth cell–derived antimicrobial peptides such as α-defensins. Various disorders, including graft-versus-host disease (GVHD), disrupt Paneth cell functions, resulting in unfavorably altered intestinal microbiota (dysbiosis), which further accelerates the underlying diseases. Current strategies to restore the gut ecosystem are bacteriotherapy such as fecal microbiota transplantation and probiotics, and no physiological approach has been developed so far. In this study, we demonstrate a novel approach to restore gut microbial ecology by Wnt agonist R-Spondin1 (R-Spo1) or recombinant α-defensin in mice. R-Spo1 stimulates intestinal stem cells to differentiate to Paneth cells and enhances luminal secretion of α-defensins. Administration of R-Spo1 or recombinant α-defensin prevents GVHD-mediated dysbiosis, thus representing a novel and physiological approach at modifying the gut ecosystem to restore intestinal homeostasis and host–microbiota cross talk toward therapeutic benefits.

Activity of therapeutic JAK 1/2 blockade in graft-versus-host disease

Blood ◽  
2014 ◽  
Vol 123 (24) ◽  
pp. 3832-3842 ◽  
Author(s):  
Silvia Spoerl ◽  
Nimitha R. Mathew ◽  
Michael Bscheider ◽  
Annette Schmitt-Graeff ◽  
Sophia Chen ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Host Disease ◽  
Graft Versus Host ◽  
Key Points

Key Points We report that ruxolitinib reduces murine GVHD via increased Treg numbers. We demonstrate the potent activity of ruxolitinib treatment in patients with corticosteroid-refractory GVHD.

Donor-derived CMV-specific T cells reduce the requirement for CMV-directed pharmacotherapy after allogeneic stem cell transplantation

Blood ◽  
2013 ◽  
Vol 121 (18) ◽  
pp. 3745-3758 ◽  
Author(s):  
Emily Blyth ◽  
Leighton Clancy ◽  
Renee Simms ◽  
Chun K. K. Ma ◽  
Jane Burgess ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Allogeneic Stem Cell Transplantation ◽  
Organ Damage ◽  
Host Disease ◽  
Graft Versus Host ◽  
Key Points

Key Points Infusion of CMV-specific T cells early posttransplant does not increase acute or chronic graft-versus-host disease. CMV-specific T cells early posttransplant reduce the need for pharmacotherapy without increased rates of CMV-related organ damage.

scholarly journals Graft-versus-host disease in recipients of male unrelated donor compared with parous female sibling donor transplants

2018 ◽  
Vol 2 (9) ◽  
pp. 1022-1031 ◽  
Author(s):  
Anita J. Kumar ◽  
Soyoung Kim ◽  
Michael T. Hemmer ◽  
Mukta Arora ◽  
Stephen R. Spellman ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Unrelated Donor ◽  
Host Disease ◽  
Graft Versus Host ◽  
Sibling Donor ◽  
Female Sibling ◽  
Key Points

Key Points Compared with parous female sibling donors, male URDs confer more aGVHD in all patients and more cGVHD in females. There was no difference in survival, relapse, or transplant mortality between recipients of parous female sibling or male URD grafts.

scholarly journals Hsp90 inhibition destabilizes Ezh2 protein in alloreactive T cells and reduces graft-versus-host disease in mice

Blood ◽  
2017 ◽  
Vol 129 (20) ◽  
pp. 2737-2748 ◽  
Author(s):  
Qingrong Huang ◽  
Shan He ◽  
Yuanyuan Tian ◽  
Yuting Gu ◽  
Pan Chen ◽  
...  
Keyword(s):  
T Cells ◽  
Protein Stability ◽  
Graft Versus Host Disease ◽  
Hsp90 Inhibition ◽  
Host Disease ◽  
Graft Versus Host ◽  
Alloreactive T Cells ◽  
Graft Versus Leukemia ◽  
Key Points ◽  
And Function

Key Points Ezh2 requires Hsp90 to maintain Ezh2 protein stability and function in alloreactive T cells. Pharmacological inhibition of Hsp90 destabilizes Ezh2 protein in alloreactive T cells and reduces GVHD but preserves graft-versus-leukemia effects.

scholarly journals Selective depletion of bone marrow T lymphocytes with anti-CD5 monoclonal antibodies: effective prophylaxis for graft-versus-host disease in patients with hematologic malignancies

Blood ◽  
1991 ◽  
Vol 78 (8) ◽  
pp. 2139-2149 ◽  
Author(s):  
JH Antin ◽  
BE Bierer ◽  
BR Smith ◽  
J Ferrara ◽  
EC Guinan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
High Risk ◽  
Graft Versus Host Disease ◽  
Graft Failure ◽  
Hematologic Malignancies ◽  
Host Disease ◽  
Graft Versus Host ◽  
High Risk Patients ◽  
Risk Patients

Seventy-one patients with hematologic malignancies received bone marrow from a histocompatible sibling (n = 48) or a partially matched relative (n = 23) that had been depleted of CD5+ T cells with either an anti-CD5 mooclonal antibody (MoAb) plus complement (anti-Leu1 + C) or an anti- CD5 MoAb conjugated to ricin A chain (ST1 immunotoxin [ST1-IT]). These patients received intensive chemoradiotherapy consisting of cytosine arabinoside, cyclophosphamide, and fractionated total body irradiation. Both anti-Leu1 + C and ST1-IT ex vivo treatments effectively depleted bone marrow of T cells (97% and 95%, respectively). Overall, primary and late graft failure each occurred in 4% of evaluable patients. The diagnosis of myelodysplasia was a significant risk factor for graft failure (P less than .001), and if myelodysplastic patients were excluded, there were no graft failures in major histocompatibility complex (MHC)-matched patients and 2 of 23 (8.7%) in MHC-mismatched patients. The actuarial risk of grade 2 to 4 acute graft-versus-host disease (GVHD) was 23% in MHC-matched patients and 50% in MHC- mismatched patients. In MHC-matched patients, acute GVHD tended to be mild and treatable with corticosteroids. Chronic GVHD was observed in 6 of 36 (17%) MHC-matched patients and none of 11 MHC-mismatched patients. There were no deaths attributable to GVHD in the MHC-matched group. Epstein-Barr virus-associated lymphoproliferative disorders were observed in 3 of 23 MHC-mismatched patients. The actuarial event-free survival was 38% in the MHC-matched patients versus 21% in the MHC- mismatched patients. However, if outcome is analyzed by risk of relapse, low-risk patients had a 62% actuarial survival compared with 11% in high-risk patients. These data indicate that the use of anti-CD5 MoAbs can effectively control GVHD in histocompatible patients, and that additional strategies are required in MHC-mismatched and high-risk patients.

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