Antilymphocyte Serum
Immunosuppression
Anemia, Aplastic
Transplantation Immunology
Chromium Isotopes
Immunological control of a murine gammaherpesvirus independent of CD8+ T cells. (1/1079)
Adult thymectomized C57 BL/6J mice were depleted of T cell subsets by MAb treatment either prior to, or after, respiratory challenge with murine gammaherpesvirus-68. Protection against acute infection was maintained when either the CD4+ or the CD8+ T cell population was greatly diminished, whereas the concurrent removal of both T cell subsets proved invariably fatal. The same depletions had little effect on mice with established infection. The results indicate firstly that both CD4+ and CD8+ T cells play a significant part in dealing with the acute infection, and secondly that virus-specific antibody contributes to controlling persistent infection with this gammaherpesvirus. (+info)Long-term results of pancreas transplantation under tacrolius immunosuppression. (2/1079)
BACKGROUND: The long-term safety and efficacy of tacrolimus in pancreas transplantation has not yet been demonstrated. The observation of prolonged pancreatic graft function under tacrolimus would indicate that any potential islet toxicity is short-lived and clinically insignificant. We report herein the results of pancreas transplantation in patients receiving primary tacrolimus immunosuppression for a minimum of 2 years. METHODS: From July 4, 1994 until April 18, 1996, 60 patients received either simultaneous pancreas-kidney transplant (n=55), pancreas transplant only (n=4), or pancreas after kidney transplantation (n=1). Baseline immunosuppression consisted of tacrolimus and steroids without antilymphocyte induction. Azathioprine was used as a third agent in 51 patients and mycophenolate mofetil in 9. Rejection episodes within the first 6 months occurred in 48 (80%) patients and were treated with high-dose corticosteroids. Antilymphocyte antibody was required in eight (13%) patients with steroid-resistant rejection. RESULTS: With a mean follow-up of 35.1+/-5.9 months (range: 24.3-45.7 months), 6-month and 1-, 2-, and 33-year graft survival is 88%, 82%, 80%, and 80% (pancreas) and 98%, 96%, 93%, and 91% (kidney), respectively. Six-month and 1-, 2-, and 3-year patient survival is 100%, 98%, 98%, and 96.5%. Mean fasting glucose is 91.6+/-13.8 mg/dl, and mean glycosylated hemoglobin is 5.1+/-0.7% (normal range: 4.3-6.1%). Mean tacrolimus dose is 6.5+/-2.6 mg/day and mean prednisone dose 2.0+/-2.9 mg/day at follow-up. Complete steroid withdrawal was possible in 31 (65%) of the 48 patients with functioning pancreases. CONCLUSIONS: These data show for the first time that tacrolimus is a safe and effective long-term primary agent in pancreas transplantation and provides excellent long-term islet function without evidence of toxicity while permitting steroid withdrawal in the majority of patients. (+info)Prospective randomized multicenter study comparing cyclosporin alone versus the combination of antithymocyte globulin and cyclosporin for treatment of patients with nonsevere aplastic anemia: a report from the European Blood and Marrow Transplant (EBMT) Severe Aplastic Anaemia Working Party. (3/1079)
We report the results of the first prospective randomized multicenter study of immunosuppressive treatment in patients with previously untreated nonsevere aplastic anemia (AA) as defined by a neutrophil count of at least 0.5 x 10(9)/L and transfusion dependence. Patients were randomized to receive cyclosporin (CSA) alone or the combination of horse antithymocyte globulin ([ATG] Lymphoglobuline; Merieux, Lyon, France) and CSA. The endpoint of the study was the hematologic response at 6 months. One hundred fifteen patients were randomized and assessable with a median follow-up period of 36 months; 61 received CSA and 54 ATG and CSA. In the CSA group, the percentage of complete and partial responders was 23% and 23%, respectively, for an overall response rate of 46%. A significantly higher overall response rate of 74% was found in the ATG and CSA group, with 57% complete and 17% partial responders (P =. 02). Compared with CSA alone, the combination of ATG and CSA resulted in a significantly higher median hemoglobin level and platelet count at 6 months. Fewer patients required a second course of treatment before 6 months due to a nonresponse. In the CSA group, 15 of 61 (25%) patients required a course of ATG before 6 months because of disease progression, compared with only 3 of 54 (6%) in the ATG and CSA group. The survival probabilities for the two groups were comparable, 93% (CSA group) and 91% (ATG and CSA group), but at 180 days, the prevalence of patients surviving free of transfusions, which excluded patients requiring second treatment because of nonresponse, death, disease progression, or relapse, was 67% in the CSA group and 90% in the ATG and CSA group (P =.001). We conclude that the combination of ATG and CSA is superior to CSA alone in terms of the hematologic response, the quality of response, and early mortality, and a second course of immunosuppression is less frequently required. (+info)Characterization of T-cell repertoire of the bone marrow in immune-mediated aplastic anemia: evidence for the involvement of antigen-driven T-cell response in cyclosporine-dependent aplastic anemia. (4/1079)
To determine whether the antigen-driven T-cell response is involved in the pathogenesis of aplastic anemia (AA), we examined the complementarity-determining region 3 (CDR3) size distribution of T-cell receptor (TCR) beta-chain (BV) subfamilies in the bone marrow (BM) of untreated AA patients. AA patients who did not respond to immunosuppressive therapy and those who obtained unmaintained remission early after cyclosporine (CyA) or antithymocyte globulin (ATG) therapy exhibited essentially a normal CDR3 size pattern. In contrast, five patients who needed continuous administration of CyA to maintain remission exhibited a skewed CDR3 size pattern in a number (>40%) of BV subfamilies suggestive of clonal predominance. The skewing of CDR3 size distribution became less pronounced in one of the CyA-dependent patients when the patient achieved unmaintained remission after a 4-year therapy with CyA, whereas it persisted longer than 7 years in the other patient requiring maintenance therapy. Sequencing of BV15 cDNA for which the CDR3 size pattern exhibited apparent clonal predominance in all CyA-dependent patients showed high homology of the amino acid sequence of the CDR3 between two different patients. These findings indicate that antigen-driven expansion of T cells is involved in the pathogenesis of AA characterized by CyA-dependent recovery of hematopoiesis. (+info)Late graft failure 8 years after first bone marrow transplantation for severe acquired aplastic anemia. (5/1079)
A 14-year-old patient with acquired very severe aplastic anemia (VSAA) underwent bone marrow transplantation (BMT) from his HLA-identical brother. Preparative therapy was cyclophosphamide (CY) 200 mg/kg over 4 days. GVHD prophylaxis was with cyclosporin A (CsA) for a year. After an 8 year follow-up during which the patient was well with normal blood counts, graft failure occurred. At this time marrow chimerism studies demonstrated that 85% of hemopoiesis was of recipient origin. The patient was re-engrafted from the same donor after conditioning with CY 200 mg/kg over 4 days plus rabbit antithymocyte globulin (ATG) 3.5 mg/kg/day for 3 days. After 140 days follow-up he has a normal blood count. The possible causes of the graft failure are discussed. This case demonstrates that, although rarely, very late graft failure may occur after BMT for AA and highlights the need for long-term monitoring even in apparently successfully transplanted patients. (+info)Monitoring anti-thymocyte globulin (ATG) in bone marrow recipients. (6/1079)
The present study was undertaken to acquire a rationale for clinical dose adjustment of anti-thymocyte globulin (ATG) to improve cost effectiveness and safety of graft-versus-host disease prophylaxis. The concentration of rabbit ATG in the serum of 12 patients was measured by ELISA and by the inhibitory effect on phytohaemagglutinin-induced blastogenesis. At 10 mg/ml ATG, 3H-thymidine incorporation was effectively blocked. Serial two-fold dilution of ATG showed that this effect decreased in a concentration-dependent manner and was lost at 10 ng/ml ATG. One hundred microlitres serum taken at day -1 to +22 post transplant effected significant inhibition of the phytohaemagglutinin-response with 49+/-12% c.p.m. (x +/- s.d.) on day +1 post transplant compared to 93+/-13% c.p.m. on day -1 (P<0.001, unpaired one-sided t-test). The rabbit-IgG was maximal at a concentration of 907+/-187 microl/ml at day 0. Subsequently, it decreased with time. While rabbit-IgG was detectable for a long period (e.g. 160 microg/ml at day +22 in patient MD), the effect on the phytohaemagglutinin-response of normal mononuclear cells lasted up to 4 days post transplant. We conclude that 90 mg/kg body weight ATG-Fresenius given prior to marrow transplant leads to sustained T cell immunosuppression post transplant. (+info)Use of a five-agent GVHD prevention regimen in recipients of unrelated donor marrow. (7/1079)
A five-agent GVHD prophylaxis programme consisting of cyclosporin A, methotrexate, anti-thymocyte-globulin, pentaglobin and metronidazol was given to 48 recipients of unrelated donor marrow with chronic myelogenous leukemia, acute leukemia, myelodysplastic syndromes, and familiar lymphocytic hemophagocytosis of an average age of 33.5 (0.6-56) years. GVHD grades II-IV occurred in 18 patients (39%) and grades III-IV in five patients (11%). Chronic GVHD developed in nine patients (23%), three limited and six extensive. Fifteen patients died. Clinical relapse was detected in eight patients. Four patients died as a consequence of the underlying disease and subsequent treatment, 11 patients died of transplant-related causes. After a median follow-up of 19 months, the overall and disease-free survival are 67% and 62%, respectively. Survival by age is as follows: 0-19 years: 12/13 patients; 20-39 years: 14/25 patients; 40-59 years: 7/10 patients. The five-agent GVHD prophylaxis regimen is effective. Matched-unrelated donor transplants can be carried out safely in patients younger than 50 years of age. The results in patients younger than 20 years of age should encourage matched-unrelated donor transplants at earlier stages of the disease. (+info)L-Arginine supplementation increases mesangial cell injury and subsequent tissue fibrosis in experimental glomerulonephritis. (8/1079)
BACKGROUND: Mesangial cell lysis in the antithymocyte serum (ATS)-induced model of glomerulonephritis is dependent on the generation of cytotoxic nitric oxide (NO) through transient induction of NO synthase (iNOS). We hypothesized that increased availability of L-arginine (L-Arg) during mesangial cell lysis might provide iNOS with increased substrate leading to increased lysis, and that this increased lysis would be reflected in more severe fibrotic disease at day 6. METHODS: To ensure whole body equilibration with high L-Arg at the time of injury, rats were pretreated with 1% L-Arg in drinking water for one week prior to the administration of ATS. Animals were sacrificed six hours after ATS injection when previous experiments had indicated iNOS induction had occurred and at six days. At six hours, plasma was obtained for L-Arg levels and nitrite/nitrate (NOx) content. Renal tissues were taken for histological evaluation of glomerular cell counts, macrophage infiltration (ED-1), and iNOS expression. Glomeruli were isolated for detection of iNOS mRNA and placed in culture to study the dependence of NO production on L-Arg concentration. In rats sacrificed at six days, L-Arg supplementation was stopped 16 hours after ATS injection. Fibrotic disease was evaluated by urinary protein excretion, histological assessment of glomerular cell number, matrix accumulation, and production of transforming growth factor-beta1 and matrix components fibronectin and plasminogen activator inhibitor type-1 (PAI-1) by isolated glomeruli in culture. RESULTS: At six hours, the glomerular cell number was significantly reduced by ATS injection (P < 0.01) and further significantly (P < 0. 05) reduced by L-Arg feeding [normal control (NC) = 64.2 +/- 1, ATS = 53.4 +/- 0.7, ATS + L-Arg = 50.8 +/- 0.7]. Disease increased macrophage infiltration and iNOS protein and iNOS mRNA levels markedly (P < 0.01), whereas L-Arg feeding did not further increase these variables. Plasma L-Arg levels (nmol/ml) were reduced by disease (NC = 121 +/- 9, ATS = 84 +/- 13, P < 0.01) and elevated by L-Arg feeding (ATS + L-Arg = 166 +/- 12, P < 0.01). Plasma NOx was significantly increased by ATS and further increased by ATS + L-Arg (P < 0.05). Production of NOx by cultured glomeruli showed striking L-Arg concentration dependence in six hours but not in normal glomeruli. In the group sacrificed at day 6, day 2 proteinuria was higher in the ATS + L-Arg group compared with the ATS alone group (P < 0.05). Measures of fibrotic disease at day 6 all showed large increases over control with ATS alone (P < 0.01), and further small, but significant increases when L-Arg was combined with ATS (P < 0.05). CONCLUSIONS: The results indicate that if given during disease induction, L-Arg supplementation can enhance iNOS-dependent tissue injury by providing increased substrate. Although the increase in injury with L-Arg supplementation was small, it led to increased fibrosis at day 6. These data predict that in diseases with repeated iNOS-dependent tissue injury, L-Arg supplementation may produce cumulative increases in tissue fibrosis. (+info)Symptoms of aplastic anemia may include fatigue, weakness, shortness of breath, pale skin, and increased risk of bleeding or infection. Treatment options for aplastic anemia typically involve blood transfusions and immunosuppressive drugs to stimulate the bone marrow to produce new blood cells. In severe cases, a bone marrow transplant may be necessary.
Overall, aplastic anemia is a rare and serious condition that requires careful management by a healthcare provider to prevent complications and improve quality of life.
* Rashes, lesions, or sores
* Redness, swelling, or inflammation
* Skin thickening or thinning
* Pigmentation changes
* Growths or tumors
* Ulcers or wounds that do not heal properly
Skin manifestations can be a symptom of a wide range of medical conditions, including:
* Infections such as bacterial, fungal, or viral infections
* Autoimmune disorders such as psoriasis, eczema, or lupus
* Cancer such as melanoma, squamous cell carcinoma, or basal cell carcinoma
* Genetic conditions such as ichthyosis or epidermolysis bullosa
* Metabolic disorders such as diabetes or kidney disease
* Nutritional deficiencies such as vitamin deficiency or malnutrition
Skin manifestations can be diagnosed through a combination of physical examination, medical history, and diagnostic tests such as biopsy, blood tests, or imaging studies. Treatment options vary depending on the underlying condition and may include topical medications, systemic medications, surgery, or lifestyle changes.
In some cases, skin manifestations can be a sign of a more serious underlying condition that requires prompt medical attention. It is important to seek medical advice if you notice any unusual changes in your skin or if you experience any symptoms such as pain, itching, or bleeding.
Jean-François Bach
Włodzimierz Ptak
Medical Research Club
Michael Woodruff
Immunosuppressive drug
Thymoglobulin
Anti-lymphocyte globulin
List of MeSH codes (D12.776)
List of MeSH codes (D12.776.124)
List of MeSH codes (A12)
List of MeSH codes (D20)
Anti-thymocyte globulin
Intestine transplantation
Aplastic anemia
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Antithymocyte globulin4
- Twenty-two patients with aplastic anemia were treated with antilymphocyte serum or antithymocyte globulin at Vanderbilt University and affiliated hospitals from 1980 to 1986. (nih.gov)
- Twenty patients received antilymphocyte serum initially while two patients received antithymocyte globulin. (nih.gov)
- Fifteen patients received fluoxymesterone 10 mg by mouth three times a day with antilymphocyte serum, and all received prednisone during the course of antilymphocyte serum or antithymocyte globulin. (nih.gov)
- Eight patients with no initial response and a patient who experienced a relapse after a complete response were re-treated with either antithymocyte globulin (six) or antilymphocyte serum (three), with four of nine patients (44 percent) having a response (three complete responses, one partial response). (nih.gov)
Globulin1
- The first polyclonal antilymphocyte globulin was used in 1967 and spawned the development of other polyclonal and monoclonal antibodies. (medscape.com)
Antibodies4
- Serum containing GAMMA-GLOBULINS which are antibodies for lymphocyte ANTIGENS . (nih.gov)
- Evidence for autoantibody positivity (eg, ANA or in the research flow method looking for antilymphocyte antibodies). (nih.gov)
- Later studies demonstrated antibodies in the sera of affected patients that reacted with the cross striations of skeletal muscle, as well as muscle membrane damage following the application of myasthenic sera to nerve-muscle preparations. (medlink.com)
- In 1974, Alman, Andrew, and Appel identified anti-AChR antibodies in human sera ( 04 ), further opening a promising new immunologic frontier in the pathogenesis of human disease. (medlink.com)
Mice1
- Immunosuppression of mice with antilymphocyte serum (ALS) or irradiation increased tumor incidence in mice inoculated with 1 X 106 PLC/PRF/5 cells to almost 100% and produced local invasiveness. (jci.org)
Content1
- PMID- 5157696 TI - [IgA in the gastric content and in the serum of eutrophic and malnourished infants]. (nih.gov)
Lymphocyte1
- Serum containing GAMMA-GLOBULINS which are antibodies for lymphocyte ANTIGENS . (bvsalud.org)
PMID1
- PMID- 5157696 TI - [IgA in the gastric content and in the serum of eutrophic and malnourished infants]. (nih.gov)
Therapy2
- Most centers include induction therapy with an antilymphocyte agent in their immunosuppressive regimens. (medscape.com)
- 31. EGFR Targeted Cetuximab-Valine-Citrulline (vc)-Doxorubicin Immunoconjugates- Loaded Bovine Serum Albumin (BSA) Nanoparticles for Colorectal Tumor Therapy. (nih.gov)
Levels2
- Careful attention to fasting blood glucose levels and upward trends in serum amylase, lipase, and glucose levels may be useful in the clinical detection of rejection, but are usually not apparent until late in the rejection process. (medscape.com)
- In addition, iron chelation may be required in chronically transfused patients who develop elevated serum ferritin levels above 1000 µg/L. (medscape.com)