Browsing by Author "Ishizawa, Kenichi"

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    Allogeneic T cells cause acute renal injury after hematopoietic cell transplantation
    (American Society of Hematology, 2023) Miyata, Masahiro; Matsuki, Eri; Ichikawa, Kazunobu; Takehara, Tomohiro; Hosokawa, Yuka; Sekiguchi, Erika; Peltier, Daniel; Reddy, Pavan; Ishizawa, Kenichi; Watanabe, Masafumi; Toubai, Tomomi; Pediatrics, School of Medicine
    Acute kidney injury (AKI) is a frequent complication of allogeneic hematopoietic cell transplantation (allo-HCT). There are many causes of AKI after allo-HCT, but it is unknown whether renal acute graft-versus-host disease (aGVHD) caused by direct allogeneic donor T-cell-mediated renal damage contributes. Here, we tested whether allogeneic donor T cells attack kidneys in murine models of aGVHD. To avoid confounding effects of nephrotoxic agents, we did not administer immunosuppressants for GVHD prophylaxis. We found that urinary N-acetyl-β-D-glucosaminidase, a marker of tubular injury, was elevated in allogeneic recipients on day 14 after allogeneic bone marrow transplantation. Donor major histocompatibility complex-positive cells were present and CD3+ T cells were increased in the glomerulus, peritubular capillaries, interstitium, and perivascular areas in the kidneys of allo-HCT recipient mice. These T cells included both CD4+ and CD8+ cells with elevated activation markers, increased exhaustion markers, and greater secretion of proinflammatory cytokines and cytotoxic proteins. Consistent with allo-T-cell-mediated renal damage, expression of neutrophil gelatinase-binding lipocalin, a marker of AKI, and elafin, a marker of aGVHD, were increased in renal tissue of allogeneic recipients. Because apoptosis of target cells is observed on histopathology of aGVHD target tissues, we confirmed that alloreactive T cells increased apoptosis of renal endothelial and tubular epithelial cells in cytotoxic T-lymphocyte assays. These data suggest that immune responses induced by donor T cells contribute to renal endothelial and tubular epithelial cell injury in allo-HCT recipients and that aGVHD may contribute to AKI after allo-HCT.
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    Exocrine Pancreatic Insufficiency Possibly Related to Atypical Chronic Graft-versus-Host Disease
    (Karger, 2023-09-06) Hosokawa, Yuka; Toubai, Tomomi; Ohya, Koichi; Nagano, Yusuke; Ishizawa, Yuki; Hosokawa, Masashi; Sato, Ryo; Watanabe, Shotaro; Yamada, Akane; Suzuki, Takuma; Aizawa, Keiko; Ito, Satoshi; Onozato, Yusuke; Peltier, Daniel; Ishizawa, Kenichi; Pediatrics, School of Medicine
    We report the case of a 66-year-old woman who presented with diarrhea and weight loss approximately 14 months after unrelated allogeneic bone marrow transplantation for acute myeloid leukemia. Her early post-transplant course was notable for mild acute skin graft-versus-host disease (GVHD) and biopsy-proven upper gastrointestinal (GI) acute GVHD, both of which resolved with treatment. She then developed weight loss and diarrhea treated with prednisolone for what was thought to be GI late acute GVHD. However, her diarrhea and weight loss persisted. Colonoscopy showed a grossly intact mucosa, and stool studies only confirmed steatorrhea. However, an atrophic pancreas was found on an abdominal computed tomography (CT) scan. Exocrine pancreatic enzymes, such as lipase and pancreatic amylase, were markedly decreased, yet pancreatic endocrine function remained intact. The patient’s diarrhea and weight loss improved upon treatment with pancrelipase. Therefore, we suggest that her exocrine pancreatic insufficiency was likely partly caused by atypical chronic GVHD.