Anti-Human Lymphocyte Globulin
Anti-Human Lymphocyte Globulin (Generic Name)
Anti-Human Lymphocyte Globulin
Lymphocytotoxic antibodies were first described in patients with infectious agents: bacteria (Mycobacterium tuberculosis, M. leprae), virus (Influenzae, herpes virus, Epstein–Barr virus), fungi and parasite. In tuberculosis, LCA have been associated with extent of lung involvement and disease severity, this association was restricted to B-cell-specific LCA.
Lymphocytotoxic antibodies are also frequent in autoimmune diseases like SLE , Sjogren’s syndrome, rheumatoid arthritis, primary biliary cirrhosis, and myasthenia gravis (Table 66.3). LCA have been reported also in non-autoimmune diseases like cancer and multiple sclerosis.
Treatment of Acute and Chronic Rejection
Imtiazuddin Shaik, … Pauline W. Chen, in Transplantation of the Liver (Third Edition), 2015
ALG (Thymoglobulin) and antithymocyte globulin (ATG) are less commonly used antilymphocyte antibody preparations. Generally considered a second choice, ALG/ATG is used when treatment with monoclonal antibodies is not suitable because of the presence of recipient antibodies. ALG/ATG preparations contain a diverse repertoire of antibodies; thus variations in effectiveness between batches frequently occurs. These products are often administered as daily 4-hour infusions, and the treatment duration varies from 1 to 2 weeks depending on the preparation and response. Dosing and specifications vary with the different commercial preparations. After a treatment course, antibodies may develop against the foreign proteins in these preparations.
John C. Magee, in Pediatric Surgery (Seventh Edition), 2012
Antilymphocyte antibodies include polyclonal preparations, such as equine antithymocyte globulin (ATGAM) and rabbit antithymocyte globulin (Thymoglobulin), and the monoclonal antibody preparations muromonab-CD3 (OKT3) and anti-CD52 (Alemtuzumab). Of these antilymphocyte agents, Thymoglobulin is currently predominant, and the use of the others is either rare or of historic interest. Antilymphocyte antibodies act by lymphodepletion, as well as by interactions with cellular receptors. The use of antilymphocyte induction regimens has declined precipitously with time.1,2 We currently restrict the use of Thymoglobulin to recipients at higher risk for immunologic graft loss, such as patients requiring retransplantation, highly sensitized patients, or black recipients. These agents are also effective in the treatment of acute cellular rejection.
Göran Sandberg, in Encyclopedia of Immunology (Second Edition), 1998
ALS as an immunosuppressive agent
ALS is used, often in combination with other immunosuppressive agents, to avoid allograft rejection. In a quadruple therapy protocol it is used with azathioprine, steroids and cyclosporine. ALS is used both as a preventive immunosuppressant, for initial treatment of rejections, and to treat steroid-resistant rejection. The mechanism of action is not fully clarified, but depletion of circulating lymphocytes does occur. This may result from either cytotoxic mechanisms or opsonization. The widest experience with ALS is from kidney transplantation, but ALS has also been used in connection with transplantation of small bowel, heart, bone marrow, liver, pancreas (or islet cells), cornea and skin.
Anesthesia for Organ Transplantation
Victor L. ScottII, … Peter J. Davis, in Smith’s Anesthesia for Infants and Children (Eighth Edition), 2011
Antilymphocyte and Antithymocyte Globulins
Antilymphocyte globulin (ALG) and antithymocyte globulin (ATG) are produced by extracting immunoglobulins from animals (usually horse or rabbit) that have been immunized with human lymphocytes or thymocytes, respectively. The IV administration of these polyclonal antibodies causes rapid and profound depletion of peripheral lymphocytes. A major limitation of all polyclonal antilymphocyte preparations is batch-to-batch heterogeneity, which results in unpredictable side effects and more importantly, variable efficacy. ALG and ATG are not typically used as first-line agents for immunosuppression. They appear to delay the onset of the first episodes of organ rejection, but the overall rates of rejection are similar to those seen with calcineurin inhibitors (Neuhaus et al., 2000). The focus of this form of therapy is as the primary immunosuppression in patients unable to tolerate calcineurin inhibitors (i.e., because of significant pretransplant renal insufficiency) and in the treatment of steroid-resistant (and possibly OKT3-resistant) rejection. Commonly observed side effects include allergic reactions, serum sickness, fever, and thrombocytopenia, as with OKT3 and other systemically infused immunoglobulins. Cytokine release syndrome (cardiovascular collapse with a hemodynamic profile similar to septic shock, noncardiogenic pulmonary edema, seizures, hyperpyrexia and renal insufficiency) may be seen with the administration of these agents, which is similar to that sometimes seen with OKT3 or any other immunoglobulin. The incidence of lymphoproliferative disease is also increased among patients who have received ALG and ATG.
Srinath Chinnakotla, … Göran B.G. Klintmalm, in Transplantation of the Liver (Third Edition), 2015
Antilymphocyte globulins have been extensively used in treatment of corticosteroid-resistant GVHD after SCT and to some extent in solid organ transplantation. In SCT an overall response rate of 30% to 59% has been reported; however, there is a high rate of relapse and also an increased rate of fungal and viral infections.16,17 The long-term survival of these patients has not been promising, with eventual median survival of less than 6 months. In a study by McCaul et al17 ATG was used in 36 patients with steroid-refractory GVHD after SCT. The response rate was highest in patients with only skin involvement (96%) and lowest in those with liver involvement (36%). The most common adverse event was infections, which occurred in 82% of the patients. Only 2 patients (6%) were alive at 15 months.17 Of more than 50 reported cases of steroid-resistant/sensitive GVHD after LT treated with r-ATG alone or in combination with corticosteroids, less than 20% have survived.18 Most of the reported cases have shown rapid recovery of symptoms and signs of the disease; however, there is high rate of relapse and progression of the disease.
Liver and pancreas transplantation immunobiology
Michael E. Lidsky, … Allan D. Kirk, in Blumgart’s Surgery of the Liver, Biliary Tract and Pancreas, 2-Volume Set (Sixth Edition), 2017
A polyclonal antilymphocyte globulin (ALG) is produced by inoculating an animal, such as a horse or rabbit, with human lymphocytes and then collecting the serum and purifying the resultant IgG. This preparation contains antibodies of multiple epitope specificities directed against lymphocyte and other cell antigens (Gaber et al, 1998; Merion et al, 1998). In the United States, the common immunogen is thymocytes, and the resultant polyclonal antibody is rabbit antithymocyte globulin (RATG). These agents promote T-cell depletion through opsonization and complement-mediated lysis (Merion et al, 1998). They also have multiple nondepletional effects that inhibit T-cell activation and function, such as crosslinking costimulation and adhesion molecules and blocking TCR signal transduction through internalization of other cell surface receptors.
Both ALG and RATG can be used as induction and rescue agents. The primary function of these agents is to reduce the number of primary effector cells below the threshold required for acute rejection and to allow for slow repopulation after the immediate posttransplant period. Although RATG is generally well tolerated, side effects include thrombocytopenia, increased viral disease, and transient cytokine release.
Infections Associated With Neutropenia And Transplantation
Emmanuel Wey, Chris Kibbler, in Antibiotic and Chemotherapy (Ninth Edition), 2010
Antilymphocyte globulins: T-cell depleting antibodies mimic the alloimmune response with activation of latent (herpes) virus, fever, cytokine release
Corticosteroids: Bacteria, Pneumocystis pneumonia, activation of hepatitis C and hepatitis B
Azathioprine: Neutropenia, uncertain role in human papillomavirus infection
Mycophenolate mofetil: Early bacterial infection, B-cell depression, late cytomegalovirus infection
Ciclosporin/tacrolimus: Increased viral replication, B-cell depression, gingival infection, intracellular pathogens
Rapamycin: Excess infections in combination with current agents (requires monitoring), idiosyncratic pulmonary syndrome, often with other respiratory pathogens
Plasmapheresis: Encapsulated bacteria
Co-stimulatory blockade: Unknown so far
Rituximab: B-cell depletion, bacterial and viral infections
Alemtuzumab: Cytomegalovirus infection, viral infection, fungal infections
Current Immunosuppressive Drugs and Clinical Use
Harrison S. Pollinger D.O., … Paul F. Gores M.D., in Cellular Transplantation, 2007
In 1960, polyclonal antilymphocyte sera was introduced for both the prevention and treatment of acute allograft rejection . This event was novel at the time because unlike any of the chemical agents used previously these biologic agents were specific and selective for immune cells. The development of hybridoma technology in the early 1970s permitted large volumes of monoclonal antibody (MAb) to be produced against T-lymphocyte receptors and other cell membrane determinants . This new field of biologic immunopharmacology has allowed for the targeting of specific cell surface markers. Moreover, newer agents are even being targeted against distinct cell protein products (cytokines). The first MAb preparation to be used clinically was OKT3, derived from a mouse source. It is reactive against the T-cell receptor (TCR) .
These biologic agents possess distinct characteristics from conventional immunosuppressive agents. They have been shown under certain conditions to promote a state of immunologic unresponsiveness that is long lasting despite the absence of immunosuppression . Several animal model experiments over the last two decades [11, 40] have been successful in inducing immunological unresponsiveness with anti-T-cell monoclonal antibodies.
Clinical Aspects of Renal Transplantation
In Pocket Companion to Brenner and Rector’s The Kidney (Eighth Edition), 2011
Mono- and Polyclonal Antilymphocyte Antibodies
The available antilymphocyte antibodies include the murine monoclonal antibody OKT3, the monoclonal antibody alemtuzumab (Campath 1-H, anti-CD52), and polyclonal horse or rabbit antihuman T-cell antibodies, ATG and thymoglobulin, respectively. These are powerful immunosuppressive agents, useful in the immediate post-transplant period in patients who are at high risk of acute rejection or who have delayed graft function (DGF). They are also widely used in the reversal of severe acute cellular rejection. Their use results in a rapid and prolonged depletion (months) of circulating T lymphocytes and is associated with a higher incidence of opportunistic infection and post-transplant lymphoproliferative disorder (PTLD).———————————————————————————————————————————————————————————————————————————————-https://www.sciencedirect.com/topics/neuroscience/anti-lymphocyte-globulin
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