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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/09/27 19:50:57」(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 Fresenius is marketed outside of the United States.

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

UpToDate Contents

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1. 肺移植後の免疫抑制の導入 induction immunosuppression following lung transplantation
2. 小児に対する腎移植における免疫抑制 immunosuppression in renal transplantation in children
3. Treatment of aplastic anemia in adults
4. 血液疾患における免疫グロブリンの静脈内投与 intravenous immune globulin in hematologic disorders
5. 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

English Journal

Tacrolimus with mycophenolate mofetil or sirolimus compared with calcineurin inhibitor-free immunosuppression (sirolimus/mycophenolate mofetil) after heart transplantation: 5-year results.

Kaczmarek I, Zaruba MM, Beiras-Fernandez A, Reimann R, Nickel T, Grinninger C, Sadoni S, Hagl C, Meiser B.SourceTransplantation Center Munich, Ludwig-Maximilians-University, Munich; Department of Cardiac Surgery, Ludwig-Maximilians-University, Munich. Electronic address: ingo.kaczmarek@med.uni-muenchen.de.
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.J Heart Lung Transplant.2013 Mar;32(3):277-84. doi: 10.1016/j.healun.2012.11.028.
BACKGROUND: Despite improvements in immunosuppressive therapy, the most advantageous combination for cardiac transplant recipients has not been established. This randomized controlled trial was performed to evaluate the efficacy and safety of 3 immunosuppressive protocols.METHODS: Between 2003 and 2
PMID 23415313

ABO-incompatible heart transplantation in early childhood: An international multicenter study of clinical experiences and limits.

Urschel S, Larsen IM, Kirk R, Flett J, Burch M, Shaw N, Birnbaum J, Netz H, Pahl E, Matthews KL, Chinnock R, Johnston JK, Derkatz K, West LJ.SourceDepartment of Pediatrics, University of Alberta, Edmonton, Alberta, Canada. Electronic address: urschel@ualberta.ca.
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.J Heart Lung Transplant.2013 Mar;32(3):285-92. doi: 10.1016/j.healun.2012.11.022. Epub 2013 Jan 8.
BACKGROUND: Intentional blood group (BG)-incompatible (ABOi) heart transplantation in childhood is emerging in many centers. Safety limits remain undetermined. In this multicenter study we have compiled experience on clinical and immunologic boundaries.METHODS: Data from six centers in Europe and No
PMID 23305695

A Novel Reduced Intensity Conditioning Regimen Induces a High Incidence of Sustained Donor-Derived Neutrophil and Platelet Engraftment after Double-Unit Cord Blood Transplantation.

Ponce DM, Sauter C, Devlin S, Lubin M, Gonzales AM, Kernan NA, Scaradavou A, Giralt S, Goldberg JD, Koehne G, Perales MA, Young JW, Castro-Malaspina H, Jakubowski A, Papadopoulos EB, Barker JN.SourceAdult Bone Marrow Transplantation Service, Department of Medicine; Weill Cornell Medical College, New York, N.Y, U.S.A.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.Biol Blood Marrow Transplant.2013 Feb 14. pii: S1083-8791(13)00079-7. doi: 10.1016/j.bbmt.2013.02.007. [Epub ahead of print]
A preparative regimen of reduced intensity that can reliably engraft cord blood (CB) and be used as an alternative to either high-dose myeloablative or non-myeloablative conditioning is needed. We evaluated double-unit CB transplantation (CBT) in 30 patients (median age 56 years range 18-69) with ac
PMID 23416850

Japanese Journal

Long-term outcome of immunosuppressive therapy for Japanese patients with lower-risk myelodysplastic syndromes

Hata Tomoko,Tsushima Hideki,Baba Maki,Imaizumi Yoshitaka,Taguchi Jun,Imanishi Daisuke,Nagai Kazuhiro,Tomonaga Masao,Miyazaki Yasushi
International Journal of Hematology 98(6), 687-693, 2013-12
… To investigate the long-term usefulness of immunosuppressive therapy (IST) for Japanese patients with lower-risk myelodysplastic syndromes, we retrospectively analyzed 29 MDS patients who were treated with cyclosporine A alone or with anti-thymocyte globulin at a single institute in Japan. …
NAID 120005372471

Effects of KIR ligand incompatibility on clinical outcomes of umbilical cord blood transplantation without ATG for acute leukemia in complete remission

Tanaka J.,Morishima Y.,Takahashi Y.,Yabe T.,Oba K.,Takahashi S.,Taniguchi S.,Ogawa H.,Onishi Y.,Miyamura K.,Kanamori H.,Aotsuka N.,Kato K.,Kato S.,Atsuta Y.,Kanda Y.
Blood cancer journal 3, e164, 2013-11
… Therefore, there were no effects of KIR ligand incompatibility in the GVH direction on single CBT outcomes for acute leukemia patients without anti-thymocyte globulin use. …
NAID 120005365910

日本国内のATGを用いたGVHD予防の現状 (第74回日本血液学会学術集会) -- (シンポジウム5 GVHD対策の最前線 : 非血縁者間末梢血幹細胞移植導入への対応)

藤重夫,福田隆浩
臨床血液 54(7), .649-652, 2013-07
NAID 40019762598

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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」「antilymphocyte antibody」「lymphocytotoxic antibody」
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