• Annals of Clinical Neurophysiology
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• 제13권1호
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• pp.58-60
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• 2011

Chronic graft-versus-host disease (GVHD) is a well-known complication of allogeneic bone marrow transplantation (BMT) and has heterogeneous manifestations, with multi-organ involvement. Recently, polymyositis (PM) was reported to be a rare manifestation of chronic GVHD. Here, we report a 30-year-old woman who was diagnosed with PM after allogeneic BMT.

• Journal of Oral Medicine and Pain
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• 제43권1호
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• pp.16-20
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• 2018

Graft-versus-host disease (GVHD) is frequent complications of hematopoietic stem cell transplantation. In the chronic GVHD (cGVHD), the oral cavity is the most commonly affected region. The clinical manifestations include erythema, ulceration, lichenoid-hyperkeratotic change in oral mucosa, dry mouth, and limitation of mouth opening. The initial treatment strategy of oral cGVHD patients is topical corticosteroid therapy in various formulation. However, corticosteroid resistance appears in some patients. We report a case of a 25-year-old male patient with oral cGVHD, who has resistance to topical corticosteroid medication, treated with 0.03% tacrolimus ointment and low-dose doxycycline. The patient showed subjective and objective improvement without side effect.

• Clinical and Experimental Pediatrics
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• 제61권11호
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• pp.371-373
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• 2018

Scabies is a highly contagious skin infestation caused by the mite, Sarcoptes scabiei var. hominis. Complex responses to scabies mites in the innate, humoral, and cellular immune systems can cause skin inflammation and pruritus. Diagnosis can be challenging because scabies resembles other common skin conditions. We report the first Korean case of scabies in a hematopoietic cell transplant (HCT) recipient, initially suspected of skin graft versus host disease (GVHD). A T-cell acute lymphocytic leukemia patient underwent a sibling-matched allogeneic HCT and developed pruritus after cell engraftment. Treatment for GVHD did not improve the symptoms. He was diagnosed with scabies 30 days after the onset of symptoms.

• IMMUNE NETWORK
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• 제13권3호
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• pp.107-110
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• 2013

Graft-versus-host disease (GVHD) is a common complication of allogeneic stem cell transplantation (allo-SCT). However, a similar syndrome has been reported in autologous stem cell transplantation (ASCT) as well. The target organs of GVHD in ASCT are the skin, liver and gastrointestinal (GI) tract, which are consistent with those in allo-SCT. Histologic findings from the skin and the mucosa of the GI tract also show similar features. Here we describe a case of autologous GVHD involving the skin of a patient who underwent ASCT for multiple myeloma. In this patient, the response to a total prednisone dose of 0.5 mg/kg/day was unsatisfactory, and the patient required more intensive and prolonged immunosuppressive therapy with slow tapering.

• IMMUNE NETWORK
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• 제11권6호
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• pp.428-430
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• 2011

We previously demonstrated that in vivo engagement of CD137, a member of TNF receptor superfamily, can delete allorective $CD4^+$ T cells through the induction of activation-induced cell death (AICD) in chronic graft-versus-host disease (cGVHD) and subsequently reverse established cGVHD. In this study, we further showed that agonistic anti-CD137 mAb was highly effective in triggering AICD of donor $CD8^+$ T cells as well as donor $CD4^+$ T cells in the $C57BL/6{\rightarrow}unirradiated$ $(C57BL/6\;{\times}\;DBA/2)F1$ acute GVHD model. Our results suggest that strong allostimulation should facilitate AICD of both alloreactive $CD4^+$ and $CD8^+$ T cells induced by CD137 stimulation. Therefore, depletion of pathogenic T cells using agonistic anti-CD137 mAb combined with potent TCR stimulation may be used to block autoimmune or inflammatory diseases mediated by T cells.

• Journal of Chest Surgery
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• 제35권6호
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• pp.471-474
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• 2002

수혈관련 이식편대숙주병은 동양인에서 개심술후에 주로 보고되는 드물지만 치명적인 병이다. 이는 신선 전혈의 수혈 전 감마선 조사로 예방할 수 있다. 61세 남자환자가 관상동맥수술을 시행받은 후 수혈 관련 이식편대숙주병이 발생하였다. 술후 환자는 두 아들에게서 2단위의 전혈을 수혈받았다. 술후 10일째 퇴원 당시 경미한 설사만 있었다. 퇴원 이틀째 지속적인 설사와 전신적 홍반 및 고열을 주소로 재입원하였다. 임상검사상 간, 신장, 소화기 및 골수의 기능 부전을 보였고, 혈역학적으로 급격히 악화되어 술후 17일에 다발성 장기 기능부전으로 사망하였다. 저자들은 본원에서 심장수술을 시행한 이래 이식편대숙주병을 처음으로 경험하였고, 이 후 전혈수혈에 대한 방침을 수정하였다.

• IMMUNE NETWORK
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• 제10권2호
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• pp.46-54
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• 2010

Background: Graft-versus-host disease (GVHD) is initiated when alloreactive donor T cells are primed by host APCs to undergo clonal expansion and maturation. Since there is a controversy regarding the role of nonhematopoietic cells in GVHD, we wanted to investigate the influence of MHC disparity on nonhematopoietic cells on the pathogenesis of GVHD in the MHC-haplomismatched C57BL/6 ($H-2^b$) or DBA/2 $(H-2^b){\rightarrow}$unirradiated ($C57BL/6{\times}DBA/2$) $F_1(BDF_1;\;H-2^{b/d})$ murine model of acute GVHD (aGVHD) or chronic GVHD (cGVHD). Methods: We generated ($BDF_1{\rightarrow}C57BL/6$), ($BDF_1{\rightarrow}DBA/2$), and ($BDF1{\rightarrow}BDF_1$) chimeras and examined GVHD-related parameters and donor cell engraftment in those chimeras. Results: Using this experimental system, we found that 1) severe aGVHD across MHC Ag barrier depends on the expression of nonhematopoietically rather than hematopoietically derived alloAgs for maximal GVHD manifestations; 2) host APCs were sufficient to break B cell tolerance to self molecules in cGVHD, whereas host APCs were insufficient to induce autoimmunity in aGVHD; 3) donor cell engraftment was greatly enhanced in the host with MHC-matched nonhematopoietic cells. Conclusion: Taken together, our results provide an insight into how MHC disparity on GVHD target organs contribute to the pathogenesis of GVHD.

• The Korean Journal of Physiology and Pharmacology
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• 제16권5호
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• pp.349-353
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• 2012

Activated T cells express inhibitory receptors such as CTLA-4 that can downregulate immune responses. Blockade of or genetic deficiency in CTLA-4 can result in autoimmunity. Therefore, strategies to increase the inhibitory function of CTLA-4 may be attractive in settings of undesirable T cell responses such as autoimmunity or transplant rejection. We have tested the hypothesis that transgenic constitutive expression of CTLA-4 can further attenuate immune responses when compared with normal inducible expression. Our results indicate that transgenic expression of CTLA-4 in mouse T cells (CTLA-4-Tg T cells) results in reduced cell cycle progression and increased apoptosis of TCR-stimulated T cells. CTLA-4-Tg T cells display reduced T cell proliferation in an in vivo model of graft versus host disease (GVHD). These results further our understanding of how CTLA-4 can be manipulated to inhibit immune responses and may help development of new therapeutic strategies for clinical settings of autoimmunity and transplantation.

• The Korean Journal of Physiology and Pharmacology
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• 제20권1호
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• pp.63-67
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• 2016

Severe graft-versus-host disease (GVHD) is an often lethal complication of allogeneic hematopoietic stem cell transplantation (HSCT). The safety of clinical-grade mesenchymal stem cells (MSCs) has been validated, but mixed results have been obtained due to heterogeneity of the MSCs. In this phase I study, the safety of bone marrow-derived homogeneous clonal MSCs (cMSCs) isolated by a new subfractionation culturing method was evaluated. cMSCs were produced in a GMP facility and intravenously administered to patients who had refractory GVHD to standard treatment resulting after allogeneic HSCT for hematologic malignancies. After administration of a single dose ($1{\times}10^6cells/kg$), 11 patients were evaluated for cMSC treatment safety and efficacy. During the trial, nine patients had 85 total adverse events and the rate of serious adverse events was 27.3% (3/11 patients). The only one adverse drug reaction related to cMSC administration was grade 2 myalgia in one patient. Treatment response was observed in four patients: one with acute GVHD (partial response) and three with chronic GVHD. The other chronic patients maintained stable disease during the observation period. This study demonstrates single cMSC infusion to have an acceptable safety profile and promising efficacy, suggesting that we can proceed with the next stage of the clinical trial.

• IMMUNE NETWORK
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• 제13권4호
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• pp.133-140
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• 2013

Since the discovery of the immunomodulation property of mesenchymal stem cells (MSCs) about a decade ago, it has been extensively investigated whether MSCs can be used for the treatment of immune-related diseases, such as graft versus-host disease (GvHD). However, how to evaluate the efficacy of human MSCs for the clinical trial is still unclear. We used an MHC-mismatched model of GvHD (B6 into BALB/c). Surprisingly, the administration of the human MSCs (hMSCs) could reduce the GvHD-related mortality of the mouse recipients and xenogeneically inhibit mouse T-cell proliferation and $IFN-{\gamma}$ production in vitro. We recently established a new protocol for the isolation of a homogeneous population of MSCs called subfractionation culturing methods (SCM), and established a library of clonal MSC lines. Therefore, we also investigated whether MSCs isolated by the conventional gradient centrifugation method (GCM) and SCM show different efficacy in vivo. Intriguingly, clonal hMSCs (hcMSCs) isolated by SCM showed better efficacy than hMSCs isolated by GCM. Based on these results, the MHC-mismatched model of GvHD may be useful for evaluating the efficacy of human MSCs before the clinical trial. The results of this study suggest that different MSC lines may show different efficacy in vivo and in vitro.