Genomes and Genes
Summary: Serum containing GAMMA-GLOBULINS which are antibodies for lymphocyte ANTIGENS. It is used both as a test for HISTOCOMPATIBILITY and therapeutically in TRANSPLANTATION.
- Scheinberg P, Nunez O, Weinstein B, Scheinberg P, Biancotto A, Wu C, et al. Horse versus rabbit antithymocyte globulin in acquired aplastic anemia. N Engl J Med. 2011;365:430-8 pubmed publisher..Funded by the Intramural Research Program of the National Institutes of Health; ClinicalTrials.gov number, NCT00260689.). ..
- Risitano A. Immunosuppressive therapies in the management of acquired immune-mediated marrow failures. Curr Opin Hematol. 2012;19:3-13 pubmed publisher..Rabbit-ATG, cyclophosphamide and alemtuzumab demonstrated a biological activity, but resulted in inferior outcome as compared with h-ATG; thus, they are not recommended as front-line therapy of aplastic anemia. ..
- Zazula R, Prucha M, Tyll T, Kieslichova E. Induction of procalcitonin in liver transplant patients treated with anti-thymocyte globulin. Crit Care. 2007;11:R131 pubmed..The results of this study indicate that ATG immunosuppressive therapy is a stimulus for the synthesis of PCT. ..
- Toor A, Rodriguez T, Bauml M, Mathews H, Shanti S, Senitzer D, et al. Feasibility of conditioning with thymoglobulin and reduced intensity TBI to reduce acute GVHD in recipients of allogeneic SCT. Bone Marrow Transplant. 2008;42:723-31 pubmed publisher..We conclude that 10 mg/kg ATG and TBI allows engraftment with a low risk of acute GVHD; however, further dose optimization of ATG is required to achieve a balance between GVHD and disease relapse. ..
- Minamimura K, Gao W, Maki T. CD4+ regulatory T cells are spared from deletion by antilymphocyte serum, a polyclonal anti-T cell antibody. J Immunol. 2006;176:4125-32 pubmed..In this study, we investigated the effect of T cell depletion by antilymphocyte serum (ALS), a polyclonal anti-T cell Ab, on CD4(+) regulatory T cells...
- Muro M, Marin L, Miras M, Moya Quiles R, Minguela A, Sanchez Bueno F, et al. Liver recipients harbouring anti-donor preformed lymphocytotoxic antibodies exhibit a poor allograft survival at the first year after transplantation: experience of one centre. Transpl Immunol. 2005;14:91-7 pubmed..In conclusion, these findings show a direct correlation between the presence of anti-donor preformed antibodies and a poor allograft survival in liver transplant. ..
- Deeks E, Keating G. Rabbit antithymocyte globulin (thymoglobulin): a review of its use in the prevention and treatment of acute renal allograft rejection. Drugs. 2009;69:1483-512 pubmed publisher..In the meantime, available clinical data suggest that rATG is an effective and generally well tolerated option for the prevention and treatment of acute renal graft rejection in renal transplant recipients. ..
- Huang Y, Parker M, Xia C, Peng R, Wasserfall C, Clarke T, et al. Rabbit polyclonal mouse antithymocyte globulin administration alters dendritic cell profile and function in NOD mice to suppress diabetogenic responses. J Immunol. 2009;182:4608-15 pubmed publisher..These studies suggest the alteration of DC profile and function by mATG may skew the Th1/Th2 balance in vivo and through such actions, represent an additional novel mechanism by which this agent provides its beneficial activities. ..
- Liu Z, Fang Y, Wang X, Wang P, Yun P, Xu H. Upregulation of molecules associated with T-regulatory function by thymoglobulin pretreatment of human CD4+ cells. Transplantation. 2008;86:1419-26 pubmed publisher..This study demonstrates that the unique effects of thymoglobulin in modulating CD4+ cells may be an important mechanism for its action in inducing immunosuppression and transplant tolerance. ..
- Kroemer A, Xiao X, Vu M, Gao W, Minamimura K, Chen M, et al. OX40 controls functionally different T cell subsets and their resistance to depletion therapy. J Immunol. 2007;179:5584-91 pubmed..Our study demonstrates that OX40 is a critical molecule in regulating survival and functions of depletion-resistant T cells; and these findings may have important clinical implications. ..
- Chung D, Korn T, Richard J, Ruzek M, Kohm A, Miller S, et al. Anti-thymocyte globulin (ATG) prevents autoimmune encephalomyelitis by expanding myelin antigen-specific Foxp3+ regulatory T cells. Int Immunol. 2007;19:1003-10 pubmed..We conclude that ATG treatment enforces the development of a dominant immunoregulatory environment which may be advantageous for the treatment of T cell-driven autoimmune diseases. ..
- Atta E, Dias D, Marra V, de Azevedo A. Comparison between horse and rabbit antithymocyte globulin as first-line treatment for patients with severe aplastic anemia: a single-center retrospective study. Ann Hematol. 2010;89:851-9 pubmed publisher..Our data suggest the superiority of horse over rabbit antithymocyte globulin as first-line treatment for severe aplastic anemia, both regarding hematological response and survival. ..
- van de Linde P, Tysma O, Medema J, Hale G, Waldmann H, Roelen D, et al. Mechanisms of antibody immunotherapy on clonal islet reactive T cells. Hum Immunol. 2006;67:264-73 pubmed..ATG and the humanized monoclonal antibodies displayed contrasting mechanisms of action. ..
- Dalle J, Dardari R, Menezes J, Cordeiro P, Champagne M, Duval M. Binding of thymoglobulin to natural killer cells leads to cell activation and interferon-gamma production. Transplantation. 2009;87:473-81 pubmed publisher..These data support the hypothesis that thymoglobulin treatment is required to observe the improvement in HSCT outcome by NK-cell alloreactivity. ..
- Burt R, Loh Y, Cohen B, Stefoski D, Stefosky D, Balabanov R, et al. Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study. Lancet Neurol. 2009;8:244-53 pubmed publisher..We evaluated the safety and clinical outcome of autologous non-myeloablative haemopoietic stem cell transplantation in patients with relapsing-remitting multiple sclerosis (MS) who had not responded to treatment with interferon beta...
- Eng H, Bennett G, Tsiopelas E, Lake M, Humphreys I, Chang S, et al. Anti-HLA donor-specific antibodies detected in positive B-cell crossmatches by Luminex predict late graft loss. Am J Transplant. 2008;8:2335-42 pubmed publisher..Thus, using BXM to preclude kidney transplantation may potentially disadvantage >60% of patients in whom BXM is not indicative of the presence of DSA. ..
- Thompson C, Steensma D. Pure red cell aplasia associated with thymoma: clinical insights from a 50-year single-institution experience. Br J Haematol. 2006;135:405-7 pubmed..However, treatment-related morbidity was high, with frequent infectious complications. ..
- Feng X, Kajigaya S, Solomou E, Keyvanfar K, Xu X, Raghavachari N, et al. Rabbit ATG but not horse ATG promotes expansion of functional CD4+CD25highFOXP3+ regulatory T cells in vitro. Blood. 2008;111:3675-83 pubmed publisher..The therapeutic effects of rATG may occur not only because of lymphocyte depletion but also enhanced Treg cell number and function. ..
- Scheinberg P, Nunez O, Young N. Retreatment with rabbit anti-thymocyte globulin and ciclosporin for patients with relapsed or refractory severe aplastic anaemia. Br J Haematol. 2006;133:622-7 pubmed..In our study, the response rate in refractory patients was inferior to what has been previously reported. ..
- Penack O, Fischer L, Gentilini C, Nogai A, Muessig A, Rieger K, et al. The type of ATG matters -- natural killer cells are influenced differentially by Thymoglobulin, Lymphoglobulin and ATG-Fresenius. Transpl Immunol. 2007;18:85-7 pubmed..Randomized trials addressing the impact of different ATGs on lymphocyte subpopulations in the clinical setting are urgently warranted. ..
- Calistri E, Tiribelli M, Battista M, Michelutti A, Corbellino M, Viale P, et al. Epstein-Barr virus reactivation in a patient treated with anti-thymocyte globulin for severe aplastic anemia. Am J Hematol. 2006;81:355-7 pubmed..We describe the case of a patient who developed an EBV infection, with the clinical features of an infectious mononucleosis, after immune suppression with cyclosporine and two courses of ATG for SAA. ..
- Neujahr D, Chen C, Huang X, Markmann J, Cobbold S, Waldmann H, et al. Accelerated memory cell homeostasis during T cell depletion and approaches to overcome it. J Immunol. 2006;176:4632-9 pubmed..These data have clinically relevant implications related to the development of novel strategies to overcome resistance to tolerance. ..
- Zand M, Vo T, Pellegrin T, Felgar R, Liesveld J, Ifthikharuddin J, et al. Apoptosis and complement-mediated lysis of myeloma cells by polyclonal rabbit antithymocyte globulin. Blood. 2006;107:2895-903 pubmed..We conclude that rATG is an effective agent for in vitro induction of apoptosis in multiple myeloma, and that exploratory clinical trials may be warranted. ..
- Samijn J, te Boekhorst P, Mondria T, Van Doorn P, Flach H, van der Meche F, et al. Intense T cell depletion followed by autologous bone marrow transplantation for severe multiple sclerosis. J Neurol Neurosurg Psychiatry. 2006;77:46-50 pubmed..The lack of efficacy, together with some serious side effects, does not favour the use of similar rigorous T cell depleting protocols in the future. ..
- Campbell P, Salam A, Ryan E, Senior P, Paty B, Bigam D, et al. Pretransplant HLA antibodies are associated with reduced graft survival after clinical islet transplantation. Am J Transplant. 2007;7:1242-8 pubmed
- van Kampen C, van de Linde P, Duinkerken G, van Schip J, Roelen D, Keymeulen B, et al. Alloreactivity against repeated HLA mismatches of sequential islet grafts transplanted in non-uremic type 1 diabetes patients. Transplantation. 2005;80:118-26 pubmed..They demonstrate the usefulness of monitoring T-cell reactivity against islet allografts to correlate immune function with graft survival and to identify conditions for preservation of beta-cell function. ..
- Piao W, Grosse J, Czwalinna A, Ivanyi P, Ganser A, Franzke A. Antigen-recognition sites of micromanipulated T cells in patients with acquired aplastic anemia. Exp Hematol. 2005;33:804-10 pubmed..Individual clonal T-cell expansion with high diversity of the antigen-binding sites among the analyzed patients argues for the predominance of private inciting epitopes in AA. ..
- Naujokat C, Berges C, Fuchs D, Sadeghi M, Opelz G, Daniel V. Antithymocyte globulins suppress dendritic cell function by multiple mechanisms. Transplantation. 2007;83:485-97 pubmed..TG and ATG-F reduce the capacity of mature DCs to stimulate allogeneic and autologous T cells. ATGs interfere with basic DC functions, suggesting that DCs are relevant targets for the immunosuppressive action of ATGs in transplantation. ..
- Nador R, Hongo D, Baker J, Yao Z, Strober S. The changed balance of regulatory and naive T cells promotes tolerance after TLI and anti-T-cell antibody conditioning. Am J Transplant. 2010;10:262-72 pubmed publisher..In conclusion, tolerance induction after conditioning in this model depends upon the ability of naturally occurring regulatory NKT and Treg cells to suppress the residual alloreactive T cells that are capable of rejecting grafts. ..
- Kaufman D, Leventhal J, Gallon L, Parker M. Alemtuzumab induction and prednisone-free maintenance immunotherapy in simultaneous pancreas-kidney transplantation comparison with rabbit antithymocyte globulin induction - long-term results. Am J Transplant. 2006;6:331-9 pubmed..Alemtuzumab induction followed by steroid-free maintenance therapy with a tacrolimus/sirolimus-based immunosuppression regimen provided an effective, safe and cost-conscious approach to SPK transplantation. ..
- Hilbrands R, Huurman V, Gillard P, Velthuis J, De Waele M, Mathieu C, et al. Differences in baseline lymphocyte counts and autoreactivity are associated with differences in outcome of islet cell transplantation in type 1 diabetic patients. Diabetes. 2009;58:2267-76 pubmed publisher..Prospective studies are needed to assess whether control of these characteristics can help increase the function of islet cell grafts during the first year posttransplantation. ..
- Ogawa N, Minamimura K, Kodaka T, Maki T. Short administration of polyclonal anti-T cell antibody (ALS) in NOD mice with extensive insulitis prevents subsequent development of autoimmune diabetes. J Autoimmun. 2006;26:225-31 pubmedTreatment of overtly diabetic NOD mice with antilymphocyte serum (ALS), a polyclonal anti-T cell antibody, leads to cure of diabetes...
- Lowsky R, Takahashi T, Liu Y, Dejbakhsh Jones S, Grumet F, Shizuru J, et al. Protective conditioning for acute graft-versus-host disease. N Engl J Med. 2005;353:1321-31 pubmed
- Scheinberg P, Fischer S, Li L, Nunez O, Wu C, Sloand E, et al. Distinct EBV and CMV reactivation patterns following antibody-based immunosuppressive regimens in patients with severe aplastic anemia. Blood. 2007;109:3219-24 pubmed
- Chen X, Zhang X, Larson C, Xia G, Kaufman D. Prolonging islet allograft survival using in vivo bioluminescence imaging to guide timing of antilymphocyte serum treatment of rejection. Transplantation. 2008;85:1246-52 pubmed publisher..aim of this study was to investigate whether early detection of rejection by BLI can aid in the timing of antilymphocyte serum (ALS) treatment for prolonging islet graft survival...
- Gillet Hladky S, de Carvalho C, Bernaud J, Bendahou C, Bloy C, Rigal D. Rabbit antithymocyte globulin inhibits monocyte-derived dendritic cells maturation in vitro and polarizes monocyte-derived dendritic cells towards tolerogenic dendritic cells expressing indoleamine 2,3-dioxygenase. Transplantation. 2006;82:965-74 pubmed..rATG polarizes in vitro Mo-DCs towards tolerogenic dendritic cells. ..
- Mohty M. Mechanisms of action of antithymocyte globulin: T-cell depletion and beyond. Leukemia. 2007;21:1387-94 pubmed
- Simon G, Parker M, Ramiya V, Wasserfall C, Huang Y, Bresson D, et al. Murine antithymocyte globulin therapy alters disease progression in NOD mice by a time-dependent induction of immunoregulation. Diabetes. 2008;57:405-14 pubmedb>Antilymphocyte serum can reverse overt type 1 diabetes in NOD mice; yet, the therapeutic parameters and immunological mechanisms underlying the ability for this agent to modulate autoimmune responses against beta-cells are unclear, ..
- Ruzek M, Waire J, Hopkins D, Lacorcia G, Sullivan J, Roberts B, et al. Characterization of in vitro antimurine thymocyte globulin-induced regulatory T cells that inhibit graft-versus-host disease in vivo. Blood. 2008;111:1726-34 pubmed..The in vitro generation of regulatory cells by anti-thymocyte globulins could provide ad-ditional therapeutic modalities for immune-mediated disease. ..
- Nash R, McSweeney P, Crofford L, Abidi M, Chen C, Godwin J, et al. High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for severe systemic sclerosis: long-term follow-up of the US multicenter pilot study. Blood. 2007;110:1388-96 pubmed..Sustained responses including a decrease in dermal fibrosis were observed exceeding those previously reported with other therapies. HDIT and autologous HCT for SSc should be evaluated in a randomized clinical trial. ..
- Brennan D, Daller J, Lake K, Cibrik D, Del Castillo D. Rabbit antithymocyte globulin versus basiliximab in renal transplantation. N Engl J Med. 2006;355:1967-77 pubmed..Patient and graft survival were similar in the two groups. (ClinicalTrials.gov number, NCT00235300 [ClinicalTrials.gov].). ..
- Hardinger K. Rabbit antithymocyte globulin induction therapy in adult renal transplantation. Pharmacotherapy. 2006;26:1771-83 pubmed..Current practice with rATG is evolving to minimize lifelong exposure to calcineurin inhibitors and corticosteroids. ..
- Haidinger M, Geyeregger R, Poglitsch M, Weichhart T, Zeyda M, Vodenik B, et al. Antithymocyte globulin impairs T-cell/antigen-presenting cell interaction: disruption of immunological synapse and conjugate formation. Transplantation. 2007;84:117-21 pubmed..In conclusion, ATG impairs T-cell/APC conjugate formation, a mechanism that may help to understand the functional inactivation of peripheral blood T-cells that have escaped cellular depletion after ATG treatment. ..
- Esposito L, Kamar N, Tkaczuk J, Abbal M, Durand D, Rostaing L. Long-term evolution of lymphocytes subsets after induction therapy based on continuous versus discontinuous administration of anti-thymocyte globulins in renal-transplant patients. Transplant Proc. 2005;37:785-7 pubmed
- Lopez M, Clarkson M, Albin M, Sayegh M, Najafian N. A novel mechanism of action for anti-thymocyte globulin: induction of CD4+CD25+Foxp3+ regulatory T cells. J Am Soc Nephrol. 2006;17:2844-53 pubmed..These novel data suggest that ATG not only may promote expansion/generation of regulatory T cells but also may be useful in future ex vivo expansion of these cells for cellular therapy in autoimmunity and clinical transplantation. ..
- Seidel M, Fritsch G, Matthes Martin S, Lawitschka A, Lion T, Potschger U, et al. In vitro and in vivo T-cell depletion with myeloablative or reduced-intensity conditioning in pediatric hematopoietic stem cell transplantation. Haematologica. 2005;90:1405-14 pubmed
- Ayuk F, Fang L, Fehse B, Zander A, Kroger N. Antithymocyte globulin induces complement-dependent cell lysis and caspase-dependent apoptosis in myeloma cells. Exp Hematol. 2005;33:1531-6 pubmed..ATG induces marked cytotoxic activity both in myeloma cell lines and in primary myeloma samples. Further elucidation of antibodies and antigens involved may pave the way for antibody-based myeloma therapy. ..
- Teramura M, Kimura A, Iwase S, Yonemura Y, Nakao S, Urabe A, et al. Treatment of severe aplastic anemia with antithymocyte globulin and cyclosporin A with or without G-CSF in adults: a multicenter randomized study in Japan. Blood. 2007;110:1756-61 pubmed..However, the relapse rate was lower in the G-CSF+ group compared with the G-CSF- group (42% vs 15% at 4 years; P = .01). Further follow-up is required to elucidate the role of G-CSF in immunosuppressive therapy for adult SAA. ..
- Kimiskidis V, Sakellari I, Tsimourtou V, Kapina V, Papagiannopoulos S, Kazis D, et al. Autologous stem-cell transplantation in malignant multiple sclerosis: a case with a favorable long-term outcome. Mult Scler. 2008;14:278-83 pubmed..It is concluded that intensive immunosuppression followed by autologous stem cell transplantation is a viable therapeutic option in patients with malignant MS unresponsive to conventional forms of treatment. ..
- Beiras Fernandez A, Chappell D, Hammer C, Thein E. Influence of polyclonal anti-thymocyte globulins upon ischemia-reperfusion injury in a non-human primate model. Transpl Immunol. 2006;15:273-9 pubmed
- Broady R, Yu J, Levings M. ATG-induced expression of FOXP3 in human CD4(+) T cells in vitro is associated with T-cell activation and not the induction of FOXP3(+) T regulatory cells. Blood. 2009;114:5003-6 pubmed publisher..These findings indicate that the notion that rATG can be used to induce Tregs in vitro for cellular therapy in vivo should be re-evaluated. ..
- Ruzek M, Neff K, Luong M, Smith K, Culm Merdek K, Richards S, et al. In vivo characterization of rabbit anti-mouse thymocyte globulin: a surrogate for rabbit anti-human thymocyte globulin. Transplantation. 2009;88:170-9 pubmed publisher..These studies characterize the depletive effects of mATG in normal mice and provide insight into mechanisms of action of Thymoglobulin. ..
- Bellin M, Kandaswamy R, Parkey J, Zhang H, Liu B, Ihm S, et al. Prolonged insulin independence after islet allotransplants in recipients with type 1 diabetes. Am J Transplant. 2008;8:2463-70 pubmed publisher..Our results suggest this immunosuppressive protocol may allow long-term graft survival. ..