• 대한이식학회지
• /
• 제28권3호
• /
• pp.165-168
• /
• 2014

The recipient candidate was a 51-year-old male with end-stage renal disease owing to diabetes mellitus. The initial immunosuppressive regimen included basiliximab for induction and tacrolimus, mycophenolate mofetil, and steroids. Urine output was 413 mL/day on the operative day and 100 mL/day on the postoperative day (POD) 1. There was no definite stenosis of the ureter or vessels. He had anuria on POD 2~4 and he had undergone hemodialysis. His serum creatinine level did not decrease. Therefore, a graft biopsy was performed on POD 4. The pathologic finding was consistent with acute calcineurin inhibitor (CNI) toxicity. There was no evidence of rejection or acute tubular necrosis. Anuria continued on POD 6; therefore, we started sirolimus instead of a CNI based regimen. Graft function was gradually recovered 1 day after reduction of CNI dose and hemodialysis was stopped. The serum creatinine level was normalized on POD 10. He was discharged on POD 21.

• IMMUNE NETWORK
• /
• 제23권6호
• /
• pp.44.1-44.16
• /
• 2023

Mesenchymal stem cells (MSCs) are effective in treating autoimmune diseases and managing various conditions, such as engraftment of allogeneic islets. Additionally, autologous and HLA-matched allogeneic MSCs can aid in the engraftment of human allogeneic kidneys with or without low doses of tacrolimus, respectively. However, HLA alloantigens are problematic because cell therapy uses more HLA-mismatched allogeneic cells than autologous for convenience and standardization. In particular, HLA-mismatched MSCs showed increased Ag-specific T/B cells and reduced viability faster than HLA-matched MSCs. In CRISPR/Cas9-based cell therapy, Cas9 induce T cell activation in the recipient's immune system. Interestingly, despite their immunogenicity being limited to the cells with foreign Ags, the accumulation of HLA alloantigen-sensitized T/B cells may lead to allograft rejection, suggesting that alloantigens may have a greater scope of adverse effects than foreign Ags. To avoid alloantigen recognition, the β2-microglobulin knockout (B2MKO) system, eliminating class-I MHC, was able to avoid rejection by alloreactive CD8 T cells compared to controls. Moreover, universal donor cells in which both B2M and Class II MHC transactivator (CIITA) were knocked out was more effective in avoiding immune rejection than single KO. However, B2MKO and CIITA KO system remain to be controlled and validated for adverse effects such as the development of tumorigenicity due to deficient Ag recognition by CD8 T and CD4 T cells, respectively. Overall, better HLA-matching or depletion of HLA alloantigens prior to cell therapy can reduce repetitive transplantation through the long-term survival of allogeneic cell therapy, which may be especially important for patients seeking allogeneic transplantation.

• Clinical and Experimental Vaccine Research
• /
• 제12권1호
• /
• pp.13-24
• /
• 2023

This systematic and meta-analysis aims to evaluate humoral and cellular responses to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine among kidney transplant recipients (KTRs). We conducted a systematic literature search across databases to evaluate seroconversion and cellular response rates in KTRs receiving SARS-CoV-2 vaccines. We extracted studies that assessed seroconversion rates described as the presence of antibody de novo positivity in KTRs following SARS-CoV-2 vaccination published up to January 23rd, 2022. We also performed meta-regression based on immunosuppression therapy used. A total of 44 studies involving 5,892 KTRs were included in this meta-analysis. The overall seroconversion rate following complete dose of vaccines was 39.2% (95% confidence interval [CI], 33.3%-45.3%) and cellular response rate was 41.6% (95% CI, 30.0%-53.6%). Meta-regression revealed that low antibody response rate was significantly associated with the high prevalence of mycophenolate mofetil/mycophenolic acid (p=0.04), belatacept (p=0.02), and antiCD25 induction therapy uses (p=0.04). Conversely, tacrolimus use was associated with higher antibody response (p=0.01). This meta-analysis suggests that postvaccination seroconversion and cellular response rates in KTRs are still low. And seroconversion rate was correlated with the type of immunosuppressive agent and induction therapy used. Additional doses of the SARS-CoV-2 vaccine for this population using a different type of vaccine are considered.

• Tuberculosis and Respiratory Diseases
• /
• 제54권4호
• /
• pp.449-458
• /
• 2003

연구배경 : Cyclosporin A(CsA)와 tacrolimus(FK506)은 현재 임상에서 널리 쓰이는 면역억제제이다. CsA와 FK506이 $I{\kappa}B/NF-{\kappa}B$ 경로에 미치는 영향에는 세포에 따라 다양한 효과가 알려져 있다. 그러나 CsA와 FK506이 기관지 상피세포에서 $I{\kappa}B/NF-{\kappa}B$ 경로에 미치는 효과에 관해서는 알려져 있지 않고, 각종 염증 세포에서의 차이에 관해서도 보고가 미미한 실정이다. 본 연구에서는 비염증세포인 기관지상피세포와, 폐의 염증에 중요한 역할을 하는 염증 세포(폐포대식세포, 단핵구, 림프구)에서 CsA와 FK506이 $I{\kappa}B{\alpha}$의 분해에 미치는 영향과 그 기전을 평가하였다. 방 법 : 비염증세포로는 BEAS-2B와 A549 세포주를 이용하였다. FK506 또는 CsA 전처치 후 TNF-${\alpha}$로 자극하고 anti-$I{\kappa}B{\alpha}$ 항체를 이용한 Western blot으로 $I{\kappa}B{\alpha}$의 분해 여부를 관찰하였다. 염증세포로는 폐포대식세포, 말초혈액 단핵구 및 림프구를 이용하였고, 역시 FK506 또는 CsA 전처치 후 TNF-${\alpha}$, IL-$1{\beta}$, LPS로 자극하고 anti-$I{\kappa}B{\alpha}$ 항체를 이용한 Western blot으로 $I{\kappa}B{\alpha}$의 분해 여부를 관찰하였다. IKK의 활성도는 GST-$I{\kappa}B{\alpha}$를 기질로 이용한 in vitro immune complex kinase assay로 평가하였다. 결 과 : 사용된 모든 세포에서 CsA와 FK506은 $I{\kappa}B{\alpha}$의 발현에 영향을 미치지 않았다. 기관지 상피세포에서 TNF-${\alpha}$ 자극에 의한 $I{\kappa}B{\alpha}$의 분해는 CsA의 전처치로 억제되었으나, FK506의 전처치로는 억제되지 않았다. 단핵구, 림프구 및 폐포대식세포에서 외부자극에 의한 $I{\kappa}B{\alpha}$의 분해는 CsA 또는 FK506의 전처치로 억제되었으나 IKK활성은 억제되지 않았다. 결 론 : CsA와 FK506은 각각 기관지 상피세포와 단핵구, 림프구, 폐포대식세포에서 외부 자극에 의한 $I{\kappa}B{\alpha}$의 분해를 억제하는데, 이는 IKK 활성화의 억제가 아닌 다른 경로를 통하는 것으로 생각된다.

• Journal of Ginseng Research
• /
• 제44권3호
• /
• pp.399-404
• /
• 2020

Korean ginseng (Panax ginseng) is associated with a variety of therapeutic effects, including antioxidative, anti-inflammatory, vasorelaxative, antiallergic, antidiabetic, and anticancer effects. Accordingly, the use of ginseng has reached an all-time high among members of the general public. However, the safety and efficacy of ginseng in transplant recipients receiving immunosuppressant drugs have still not been elucidated. Transplantation is the most challenging and complex of surgical procedures and may require causation for the use of ginseng. In this regard, we have previously examined the safety, immunological benefits, and protective mechanisms of ginseng with respect to calcineurin inhibitor-based immunosuppression, which is the most widely used regimen in organ transplantation. Using an experimental model of calcineurin inhibitor-induced organ injury, we found that ginseng does not affect drug levels in the peripheral blood and tissue, favorably regulates immune response, and protects against calcineurin inhibitor-induced nephrotoxicity and pancreatic islet injury. On the basis of our experimental studies and a review of the related literature, we propose that ginseng may provide benefits in organ transplant recipients administered calcineurin inhibitors. Through the present review, we aimed to briefly discuss our current understanding of the therapeutic benefits of ginseng related to transplant patient survival.

• 대한두개안면성형외과학회지
• /
• 제13권2호
• /
• pp.85-94
• /
• 2012

The world's first face transplantation was performed in France, in 2005. Since then, 21 cases of face transplantation have been performed. Face transplantation is one of the most prominent part of composite tissue allotransplantation (CTA) along with hand transplantation. Since these fields are not deal with life-saving organs, there are many arguments about immunosuppression therapy. Recent paradigm of face transplantation shows that surgical ranges are expanded from partial face transplantation to full face transplantation. Most immunosuppression protocols are triple therapy, which consists of tacrolimus (FK-506), mycophenolate mofetil and prednisolone. Anatomical researches, immunosuppression, and immunotolerance take great parts in the researches of CTA. The medical fields directly related to face transplantation are microsurgery, immunology, and transplantation. Nowadays, each field is performed widely. Therefore people, even medical teams think face transplantation could be easily realized, sooner or later. But there are lots of things that should be prepared for not only practice and immunosuppression therapy but also for the cooperation with relevant fields. That's the reason why only 21 cases of face transplantation have been done, while more than 70 cases of hand transplantation have been done in the past years. Especially in Korea, brain death patients are not enough even for organ transplantation and furthermore there are some troubles in taking part in the society of transplantation. Face transplantation has lots of problems concerning variable medical fields, administration, society, ethics, and laws. Therefore, for the realization of face transplantation in Korea, not only medical skills but also political powers are needed.

• 감성과학
• /
• 제19권2호
• /
• pp.27-34
• /
• 2016

본 연구에서는 카모마일, 라벤더, 샌달우드를 혼합한 아로마 혼합오일(CLS)과 면역억제제(FK506)의 아토피 피부염 치료효과를 알아보기 위하여 혈청 중 IgE(Immunoglobulin E)와 IgG1(Immunoglobulin G1)의 수준의 감소효과, 피부 임상지수를 이용한 육안평가 등을 실시하였다. 그 결과 IgE 수준을 낮추는데는 CLS가 더 효과적이었고, IgG1 수준을 감소시키는 데에는 FK506이 더 효과적인 것으로 나타났다. 육안평가 결과를 통하여 아토피 피부염을 가진 마우스에 FK506과 CLS를 도포한 후 2주까지는 아토피 증상을 더 악화시켰으며 4주후부터는 증상완화가 현저하게 나타남을 확인할 수 있었다. 특히 FK506의 효과가 두드러졌는데 이는 IgG1 수준감소와 관련이 있는 것으로 사료되며 이와 관련하여 보다 심도있는 실험 조사가 필요하겠다. 이상의 결과로부터 카모마일 저먼, 라벤더, 샌달우드의 아로마 혼합오일이 아토피 피부염의 개선에 효능이 있음이 인정되었고 이와 같이 장기간 피부에 도포하여 치료하는 경우 CLS가 아토피 치료의 한 방법으로서 가능성이 보임을 확인하였음에 본 연구의 의의가 있다.

• Pediatric Infection and Vaccine
• /
• 제25권2호
• /
• pp.82-90
• /
• 2018

목적: 16년간단일기관에서시행된간이식후소아에서발생한세균감염합병증의빈도와특징을분석하기위해시행되었다. 방법: 2000년 1월부터 2015년 6월까지 서울대학교병원에서 간이식을 시행 받은 207명 소아 중 다장기 이식이나 2번 이상의 간이식을 시행 받은 18명을 제외한 189명이 연구에 포함되었다. 감염 증상과 더불어 병원체가 증명된 세균 감염 만을 대상으로 하여 감염성 질환의 종류 및 발생 시기 등을 조사하였다. 결과: 189명의 간이식 소아의 중간연령은 24개월(2개월-16세)이었으며, 수술 후 1년 간 추적 관찰 하였다. 총 87명(46.0%)에서 132건(0.7건/명)의 세균 감염이 발생하였다. 균혈증(n=39, 29.5%), 복막염(n=28, 21.2%), 요로감염(n=25, 18.9%), 폐렴(n=20,15.2%)의 순이었다. 그람양성균이 66건(50%), 그람음성균이 66건(50%)에서 확인되었다. 세균 감염은 이식 후 1개월 이내에 84건(63.6%), 1-6개월에 32건(24.2%), 6개월 이후에 16건(12.1%)으로 이식 초기에 유의하게 많았다(P<0.05). 가장 흔한 그람양성균은 Staphylococcus aureus (n=20, 15.2%) 와 Enterococcus species (n=20, 15.2%) 였으며, 그람음성균은 Klebsiella species (n=18, 13.6%), Enterobacter species (n=13, 9.8%), Escherichia coli (n=11, 8.3%) 순으로 많았다. 이 중 7명(41%)이 감염성 합병증으로 사망하였다(균혈증 4명, 복막염 1명, 폐렴 2명). 결론: 지난 16년 간 본 기관에서 소아에게 시행한 간이식 후 발생한 감염성 합병증의 빈도와 종류는 기존의 연구들과 비슷하였다. 간이식 후 소아에서 세균 감염 합병증은 이식 후 1개월 이내에 가장 많이 발생하며, 1개월이 지난 후에도 중증의 세균 감염으로 인한 사망률이 높아 6개월 전까지는 면밀한 세균 감염 합병증의 진단 및 치료가 필수적이다. 본 연구를 통해 향후 간이식의 예후 향상을 위한 연구의 토대가 될 것을 기대한다.