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a family of proteins found in blood and milk and muscle and in plant seed

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グロブリン(動植物組織内の純蛋白(たんぱく)質の総称)

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/02/21 15:41:58」(JST)

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Anti-thymocyte globulin (ATG) is an infusion of horse or rabbit-derived antibodies against human T cells, which is used in the prevention and treatment of acute rejection in organ transplantation and therapy of aplastic anemia.

Uses

Two antithymocyte globulin (ATG) agents licensed for clinical use in the United States are Thymoglobulin (rabbit ATG, rATG, Genzyme) and Atgam (equine ATG, eATG, Pfizer). Thymoglobulin and Atgam are currently licensed for use in the treatment of renal allograft rejection; Atgam is additionally licensed for use in the treatment of aplastic anemia. Both drugs are used in off-label applications, especially as immunosuppression induction agents before and/or during kidney transplantation. An rATG product made by Neovii Pharmaceuticals is marketed outside of the United States under the name Grafalon .

ATG administration very substantially reduces immune competence in patients with normal immune systems, through a combination of actions, some explicitly understood and some more hypothetical. rATG in particular effects large reductions (through cell lysis) in the number of circulating T-lymphocytes, hence preventing (or at least delaying) the cellular rejection of transplanted organs. However, medical opinion remains divided as to when the benefit of this profound reduction in T-cells outweighs the concomitant increased risks of infection and malignancy.

In the United States it is frequently given at the time of the transplant to prevent graft-versus-host disease,^[1] although many European centers prefer to reserve its use for the treatment of steroid-resistant acute rejection, as European centres generally serve more homogeneous populations and rejection tends to be less of a problem.^{[citation needed]}

Complications and alternatives

ATG use can induce cytokine release syndrome, and has been thought to increase the risk of post-transplant lymphoproliferative disorder (PTLD); however, this association may not apply when lower dosing regimens are used. There is some evidence to suggest that inducing immunosuppression with rATG at organ transplantation may create conditions in the patient's immune system favorable to the development of immunological tolerance, but the exact basis for such a development remains largely speculative. Temporary depletion of the T-cell population at the time of the transplant also risks delayed acute rejection, which may be missed and cause severe damage to the graft.

Anti-IL-2Rα receptor antibodies such as basiliximab and daclizumab are increasingly being used in place of ATG as an induction therapy, as they do not cause cytokine release syndrome and (theoretically) improve the development of tolerance.

The cytokine release syndrome associated with ATG administration frequently causes high grade fevers (over 39^oC), chills, and possibly rigors during administration, for which reason steroids (normally methylprednisolone), diphenhydramine 25–50 mg, and acetaminophen 650 mg are usually co-administered. Such adverse reactions can often be controlled by slowing the infusion rate.

History

The first report of immunizing an animal of one species (Guinea pig) against the immune cells of another species (mouse lymphocytes) was by Metchnikoff in 1899. He reported injecting cells recovered from mouse lymph nodes into Guinea pigs and waiting for the immunization to result in the accumulation of anti-mouse antibodies in the Guinea pig blood. When he subsequently collected serum from these Guinea pigs and injected it into normal mice he observed a marked depletion in the number of circulating mouse lymphocytes.

Status in graft-versus-host disease

Rabbit ATG has been used in two randomised trials to reduce acute Graft versus Host (aGVH) disease in recipients receiving progenitor cell transplants.^[2] While higher doses (15 mg/kg) reduced aGVH this was offset by increased infections. However a long term follow up showed that at both high and low (7.5 mg/kg) doses chronic GVH (cGVH) was reduced.^[3] A similar trial of anti-lymphocyte globulin showed a trend in reduction of aGVH that was not statistically significant, but a reduction in cGVH.^[4] The Canadian Blood and Marrow Transplant Group is currently conducting the first randomised trial in cGVH using an even lower dose of rabbit ATG (4.5 mg/kg) in an attempt to confirm these observations. The endpoint is the reduction in the proportion of patients with cGVH at 1 year, off immunosuppressants. ^[5]

References

^ Antithymocyte globulin entry in the public domain NCI Dictionary of Cancer Terms
^ Bacigalupo A, Lamparelli T, Bruzzi P, et al. (November 2001). "Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO)". Blood. 98 (10): 2942–7. doi:10.1182/blood.V98.10.2942. PMID 11698275.
^ Bacigalupo A, Lamparelli T, Barisione G, et al. (May 2006). "Thymoglobulin prevents chronic graft-versus-host disease, chronic lung dysfunction, and late transplant-related mortality: long-term follow-up of a randomized trial in patients undergoing unrelated donor transplantation". Biology of Blood and Marrow Transplantation. 12 (5): 560–5. doi:10.1016/j.bbmt.2005.12.034. PMID 16635791.
^ Finke J, Bethge WA, Schmoor C, et al. (September 2009). "Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial". The Lancet Oncology. 10 (9): 855–64. doi:10.1016/S1470-2045(09)70225-6. PMID 19695955.
^ Thymoglobulin to prevent chronic graft versus host disease in hematopoietic progenitor cell transplantation patients Archived December 13, 2010, at the Wayback Machine.

UpToDate Contents

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1. 再生不良性貧血：予後および治療 aplastic anemia prognosis and treatment
2. 成人の腎移植における免疫抑制誘導療法 induction immunosuppressive therapy in renal transplantation in adults
3. 移植片対宿主病の予防および治療に使用される免疫抑制剤の概要 overview of immunosuppressive agents used for prevention and treatment of graft versus host disease
4. HLA-haploidentical hematopoietic cell transplantation
5. 急性腎同種移植片拒絶反応：治療 acute renal allograft rejection treatment

English Journal

Bortezomib may stabilize pediatric renal transplant recipients with antibody-mediated rejection.

Pearl MH1, Nayak AB2, Ettenger RB2, Puliyanda D3, Palma Diaz MF4, Zhang Q4, Reed EF4, Tsai EW2.
Pediatric nephrology (Berlin, Germany).Pediatr Nephrol.2016 Aug;31(8):1341-8. doi: 10.1007/s00467-016-3319-3. Epub 2016 Apr 5.
BACKGROUND: Current therapeutic strategies to effectively treat antibody-mediated rejection (AMR) are insufficient. Thus, we aimed to determine the benefit of a therapeutic protocol using bortezomib for refractory C4d + AMR in pediatric kidney transplant patients.METHODS: We examined seven patients
PMID 27048228

Regulatory T Cell Infusion Can Enhance Memory T Cell and Alloantibody Responses in Lymphodepleted Nonhuman Primate Heart Allograft Recipients.

Ezzelarab MB1, Zhang H1, Guo H1, Lu L1, Zahorchak AF1, Wiseman RW2, Nalesnik MA3, Bhama JK4, Cooper DK1,5, Thomson AW1,5.
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.Am J Transplant.2016 Jul;16(7):1999-2015. doi: 10.1111/ajt.13685. Epub 2016 Mar 17.
The ability of regulatory T cells (Treg) to prolong allograft survival and promote transplant tolerance in lymphodepleted rodents is well established. Few studies, however, have addressed the therapeutic potential of adoptively transferred, CD4(+) CD25(+) CD127(-) Foxp3(+) (Treg) in clinically relev
PMID 26700196

Antithymocyte Globulin Induction Therapy in Liver Transplant: Old Drug, New Uses.

Petite SE1, Bollinger JE2, Eghtesad B2.
The Annals of pharmacotherapy.Ann Pharmacother.2016 Jul;50(7):592-8. doi: 10.1177/1060028016647974. Epub 2016 May 4.
OBJECTIVE: To review the use of rabbit antithymocyte globulin (rATG) induction therapy in liver transplant recipients.DATA SOURCES: A MEDLINE literature search (inception to March 2016) was conducted using the search terms rabbit antithymocyte globulin, liver transplantation, and induction Reference
PMID 27147705

Japanese Journal

Cord Blood Transplantation Following Reduced-intensity Conditioning for Adult-onset Inherited Hemophagocytic Lymphohistiocytosis

Internal Medicine 55(6), 667-671, 2016
NAID 130005138087

Successful Allogeneic Stem Cell Transplantation for Severe Aplastic Anemia after Treatment of Lymphoproliferative Disorder Caused by Rabbit Antithymocyte Globulin

Internal Medicine 54(24), 3197-3200, 2015
NAID 130005114245

再生不良性貧血に対する造血幹細胞移植

臨床血液 56(10), 2153-2159, 2015
NAID 130005103281

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★リンクテーブル★

リンク元	「抗リンパ球血清」「ウマ由来抗ヒト胸腺細胞免疫グロブリン」「抗胸腺細胞グロブリン」「anti-thymocyte globulin」「antilymphocyte antibody」
関連記事	「globuli」