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1
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Parajuli S, Hidalgo LG, Foley D. Immunology of simultaneous liver and kidney transplants with identification and prevention of rejection. FRONTIERS IN TRANSPLANTATION 2022; 1:991546. [PMID: 38994375 PMCID: PMC11235231 DOI: 10.3389/frtra.2022.991546] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Accepted: 10/12/2022] [Indexed: 07/13/2024]
Abstract
Simultaneous liver and kidney (SLK) transplantation is considered the best treatment modality among selected patients with both chronic kidney disease (CKD) and end-stage liver disease (ESLD). Since the first SLK transplant in 1983, the number of SLK transplants has increased worldwide, and particularly in the United States since the implementation of the MELD system in 2002. SLK transplants are considered a relatively low immunological risk procedure evidenced by multiple studies displaying the immunomodulatory properties of the liver on the immune system of SLK recipients. SLK recipients demonstrate lower rates of both cellular and antibody-mediated rejection on the kidney allograft when compared to kidney transplant-alone recipients. Therefore, SLK transplants in the setting of preformed donor-specific HLA antibodies (DSA) are a common practice, at many centers. Acceptance and transplantation of SLKs are based solely on ABO compatibility without much consideration of crossmatch results or DSA levels. However, some studies suggest an increased risk for rejection for SLK recipients transplanted across high levels of pre-formed HLA DSA. Despite this, there is no consensus regarding acceptable levels of pre-formed DSA, the role of pre-transplant desensitization, splenectomy, or immunosuppressive management in this unique population. Also, the impact of post-transplant DSA monitoring on long-term outcomes is not well-studied in SLK recipients. In this article, we review recent and relevant past articles in this field with a focus on the immunological risk factors among SLK recipients, and strategies to mitigate the negative outcomes among them.
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Affiliation(s)
- Sandesh Parajuli
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - Luis G. Hidalgo
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - David Foley
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
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2
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López-Trascasa M, Alonso-Melgar Á, Melgosa-Hijosa M, Espinosa-Román L, Lledín-Barbancho MD, García-Fernández E, Rodríguez de Córdoba S, Sánchez-Corral P. Case Report: Combined Liver-Kidney Transplantation to Correct a Mutation in Complement Factor B in an Atypical Hemolytic Uremic Syndrome Patient. Front Immunol 2021; 12:751093. [PMID: 34721423 PMCID: PMC8551365 DOI: 10.3389/fimmu.2021.751093] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Accepted: 09/27/2021] [Indexed: 12/12/2022] Open
Abstract
Pathogenic gain-of-function variants in complement Factor B were identified as causative of atypical Hemolytic Uremic syndrome (aHUS) in 2007. These mutations generate a reduction on the plasma levels of complement C3. A four-month-old boy was diagnosed with hypocomplementemic aHUS in May 2000, and he suffered seven recurrences during the following three years. He developed a severe hypertension which required 6 anti-hypertensive drugs and presented acrocyanosis and several confusional episodes. Plasma infusion or exchange, and immunosuppressive treatments did not improve the clinical evolution, and the patient developed end-stage renal disease at the age of 3 years. Hypertension and vascular symptoms persisted while he was on peritoneal dialysis or hemodialysis, as well as after bilateral nephrectomy. C3 levels remained low, while C4 levels were normal. In 2005, a heterozygous gain-of-function mutation in Factor B (K323E) was found. A combined liver and kidney transplantation (CLKT) was performed in March 2009, since there was not any therapy for complement inhibition in these patients. Kidney and liver functions normalized in the first two weeks, and the C3/C4 ratio immediately after transplantation, indicating that the C3 activation has been corrected. After remaining stable for 4 years, the patient suffered a B-cell non-Hodgkin lymphoma that was cured by chemotherapy and reduction of immunosuppressive drugs. Signs of liver rejection with cholangitis were observed a few months later, and a second liver graft was done 11 years after the CLKT. One year later, the patient maintains normal kidney and liver functions, also C3 and C4 levels are within the normal range. The 12-year follow-up of the patient reveals that, in spite of severe complications, CLKT was an acceptable therapeutic option for this aHUS patient.
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Affiliation(s)
- Margarita López-Trascasa
- Departamento de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.,Complement Research Group, Hospital La Paz Institute for Health Research (IdiPAZ), La Paz University Hospital, Madrid, Spain
| | | | - Marta Melgosa-Hijosa
- Complement Research Group, Hospital La Paz Institute for Health Research (IdiPAZ), La Paz University Hospital, Madrid, Spain.,Pediatric Nephrology Service, La Paz University Hospital, Madrid, Spain
| | - Laura Espinosa-Román
- Complement Research Group, Hospital La Paz Institute for Health Research (IdiPAZ), La Paz University Hospital, Madrid, Spain.,Pediatric Nephrology Service, La Paz University Hospital, Madrid, Spain
| | | | | | - Santiago Rodríguez de Córdoba
- Department of Molecular Biomedicine, Centro de Investigaciones Biológicas (CSIC), Madrid, Spain.,Center for Biomedical Network Research on Rare Diseases (CIBERER), Madrid, Spain
| | - Pilar Sánchez-Corral
- Complement Research Group, Hospital La Paz Institute for Health Research (IdiPAZ), La Paz University Hospital, Madrid, Spain.,Center for Biomedical Network Research on Rare Diseases (CIBERER), Madrid, Spain
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Ranawaka R, Dayasiri K, Gamage M. Combined liver and kidney transplantation in children and long-term outcome. World J Transplant 2020; 10:283-290. [PMID: 33134116 PMCID: PMC7579435 DOI: 10.5500/wjt.v10.i10.283] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 09/17/2020] [Accepted: 09/25/2020] [Indexed: 02/06/2023] Open
Abstract
Combined liver-kidney transplantation (CLKT) is a rarely performed complex surgical procedure in children and involves transplantation of kidney and either whole or part of liver donated by the same individual (usually a cadaver) to the same recipient during a single surgical procedure. Most common indications for CLKT in children are autosomal recessive polycystic kidney disease and primary hyperoxaluria type 1. Atypical haemolytic uremic syndrome, methylmalonic academia, and conditions where liver and renal failure co-exists may be indications for CLKT. CLKT is often preferred over sequential liver-kidney transplantation due to immunoprotective effects of transplanted liver on renal allograft; however, liver survival has no significant impact. Since CLKT is a major surgical procedure which involves multiple and complex anastomosis surgeries, acute complications are not uncommon. Bleeding, thrombosis, haemodynamic instability, infections, acute cellular rejections, renal and liver dysfunction are acute complications. The long-term outlook is promising with over 80% 5-year survival rates among those children who survive the initial six-month postoperative period.
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Affiliation(s)
- Randula Ranawaka
- Department of Paediatrics, Faculty of Medicine, University of Colombo and Lady Ridgeway Hospital for Children, Colombo 0094, Sri Lanka
| | - Kavinda Dayasiri
- Department of Paediatrics, Base Hospital Mahaoya, Mahaoya 0094, Sri Lanka
| | - Manoji Gamage
- Department of Clinical Nutrition, Lady Ridgeway Hospital for Children, Colombo 0094, Sri Lanka
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4
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Affiliation(s)
- R M Binns
- ARC, Institute of Animal Physiology, Babraham, Cambridge, CB2 4AT
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Ganschow R, Hoppe B. Review of combined liver and kidney transplantation in children. Pediatr Transplant 2015; 19:820-6. [PMID: 26354144 DOI: 10.1111/petr.12593] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/06/2015] [Indexed: 12/25/2022]
Abstract
In this review, we focused on CLKT with regard to indication, results, outcome, and future developments. PH1 is one of the most common diagnoses for adult and pediatric patients qualifying for CLKT. The other major indication for combined transplantation is ARPKD. CLKT appears to be superior to sequential liver and kidney transplantation in the majority of patients and overall results following CLKT are now good, even in small children. Clinical observations suggest that there is an immunological advantage of CLKT in comparison with isolated liver or kidney transplantation. More clinical studies are necessary to identify the best candidates for CLKT while the availability of donor organs is low.
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Affiliation(s)
- Rainer Ganschow
- Department of Pediatrics, University Medical Center, Bonn, Germany
| | - Bernd Hoppe
- Department of Pediatrics, University Medical Center, Bonn, Germany
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6
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Carbone M, Cockwell P, Neuberger J. Hepatitis C and kidney transplantation. Int J Nephrol 2011; 2011:593291. [PMID: 21755059 PMCID: PMC3132687 DOI: 10.4061/2011/593291] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2011] [Revised: 03/05/2011] [Accepted: 04/13/2011] [Indexed: 12/17/2022] Open
Abstract
Hepatitis C virus (HCV) infection is relatively common among patients with end-stage kidney disease (ESKD) on dialysis and kidney transplant recipients. HCV infection in hemodialysis patients is associated with an increased mortality due to liver cirrhosis and hepatocellular carcinoma. The severity of hepatitis C-related liver disease in kidney transplant candidates may predict patient and graft survival after transplant. Liver biopsy remains the gold standard in the assessment of liver fibrosis in this setting. Kidney transplantation, not haemodialysis, seems to be the best treatment for HCV+ve patients with ESKD. Transplantation of kidneys from HCV+ve donors restricted to HCV+ve recipients is safe and associated with a reduction in the waiting time. Simultaneous kidney/liver transplantation (SKL) should be considered for kidney transplant candidates with HCV-related decompensated cirrhosis. Treatment of HCV is more complex in hemodialysis patients, whereas treatment of HCV recurrence in SLK recipients appears effective and safe.
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Affiliation(s)
- Marco Carbone
- Liver Unit, Queen Elizabeth Hospital, Birmingham B15 2TH, UK
| | - Paul Cockwell
- Department of Nephrology, Queen Elizabeth Hospital, Birmingham B15 2TH, UK
| | - James Neuberger
- Liver Unit, Queen Elizabeth Hospital, Birmingham B15 2TH, UK
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7
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Geissler E, Scherer M, Graeb C. Soluble donor MHC class I gene transfer to thymus promotes allograft survival in a high-responder heart transplant model. Transpl Int 2011. [DOI: 10.1111/j.1432-2277.2000.tb02082.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Van Wagner LB, Baker T, Ahya SN, Norvell JP, Wang E, Levitsky J. Outcomes of patients with hepatitis C undergoing simultaneous liver-kidney transplantation. J Hepatol 2009; 51:874-80. [PMID: 19643508 DOI: 10.1016/j.jhep.2009.05.025] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2009] [Revised: 05/05/2009] [Accepted: 05/27/2009] [Indexed: 02/08/2023]
Abstract
BACKGROUND/AIMS The number of simultaneous liver-kidney transplants (SLK) has increased since the MELD era. Data on short- and long-term outcomes of hepatitis C virus positive (HCV+) SLK compared to HCV+ liver transplant alone (LTA) recipients are limited. METHODS A case-control study comparing outcomes of HCV+SLK versus transplant year-matched HCV+ LTA (1:1) was performed. RESULTS 38/142 (26.7%) SLK recipients were HCV+. LTA controls had lower MELD (17.4+/-8.6) at transplant than SLK (34.5+/-6.6) (p=0.001). There were increased early post-transplant infection episodes in SLK (56.3%) versus LTA (21.6%) (p=0.001) and a trend towards increased early mortality in the SLK group (p=0.08). However, there was no difference in long-term patient and graft survival, time to HCV recurrence, % >or=stage 2 fibrosis, renal function, and graft function between the groups. Ten SLK recipients were treated for HCV recurrence with pegylated interferon+ribavirin: two had sustained virologic response, five stopped due to side effects, and three had no response. None had liver or kidney rejection on treatment. CONCLUSION Our data represent the largest analysis of HCV+ SLK outcomes to date. We demonstrate increased early complications in SLK versus LTA recipients, likely due to being more critically ill at transplant (higher MELD) and complications unrelated to HCV within the first year. However, long-term outcomes, i.e. HCV recurrence, graft/renal dysfunction, are similar to LTA. In addition, while data are limited, treatment of HCV recurrence with interferon appeared safe in our SLK recipients.
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Affiliation(s)
- Lisa B Van Wagner
- Division of Hepatology, Medicine Northwestern University, Chicago, IL, USA
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9
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Renal Graft Outcome in Simultaneous Kidney Transplantation Combined With Other Organs: Experience of a Single Center. Transplant Proc 2008; 40:3424-7. [DOI: 10.1016/j.transproceed.2008.06.111] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2008] [Accepted: 06/04/2008] [Indexed: 11/21/2022]
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Staines NA, O'Neill GJ, Guy K, Davies DA. Xenoantisera against lymphoid cells: specificity and use in monitoring purification of mouse and human histocompatibility antigens. TISSUE ANTIGENS 2008; 3:1-21. [PMID: 4804080 DOI: 10.1111/j.1399-0039.1973.tb00973.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
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Gutiérrez Baños J, Portillo Martín J, Ballestero Diego R, Zubillaga Guerrero S, Ramos Barselo E, Campos Sañudo J. [Renal graft outcome in patients with associated liver transplant]. Actas Urol Esp 2008; 32:220-4. [PMID: 18409472 DOI: 10.1016/s0210-4806(08)73816-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
INTRODUCTION Nearly 50% of liver transplant recipients have some degree of renal failure; patients in haemodialysis treatment have a higher risk of suffering hepatic diseases related to viral infections or concomitant pathologies. Improvement in surgical and organ preservation techniques and immunosuppressive therapy has permitted multiorganic transplants in patients needing both liver and kidney organs. OBJECTIVES To review our results in renal transplants in those patients with liver and kidney transplants. MATERIAL AND METHOD Retrospective study of the 15 patients with liver and kidney transplants performed in our Hospital. We have reviewed patients main characteristics, liver and renal failure causes, renal graft and patient outcome and complications relate to renal transplant. RESULTS Between 1975 and December 2006 we performed 1483 kidney transplants and between 1991 and December 2006, 409 liver transplants. We performed multiorganic liver and kidney transplants to 15 patients (4 women and 11 men). The average for liver transplant recipients was 52.5+/-9.3 years (range 37-61) and for kidney transplant recipients was 51+/-12.5 years (35-66). Cold ischemia was 6.4+/-5.4 hours (6-8) in simultaneous liver-kidney transplant and 20.5+/-5.4 (8-27 hours) in non-simultaneous ones. Three patients had a renal transplant before the liver one (two functioning which had no changes after hepatic transplant but the other was lost due to IgA glomeruloneprhitis relapse and received a simultaneous kidney-liver transplant). Six patients received a simultaneous kidney-liver transplant and eight patients a renal transplant between 16 and 83 months (x=50.5+/-25.9 months) after the liver transplant. A renal graft was lost due to renal vein thrombosis and two due to IgA relapse; the others were functioning between 6 and 264 months of follow-up (x=92.5+/-66.7) with creatinine levels of 1.86+/-mg/100, (range 1-4.5). Four patients died due to hepatic failure between 8 months and 21 years after renal transplant and another died of oesophagus cancer 14 years after the kidney transplant, in all cases with functioning renal graft. There were no cases of kidney graft acute rejection in simultaneous transplants but there were five in non-simultaneous ones. Immunotherapy was based on steroids and tacrolimus. CONCLUSIONS Liver-kidney transplants are worthy options in patients with hepatic and renal end failure. Acute rejection seems to have fewer incidences in simultaneous liver-kidney transplantation.
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12
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Transplantation foie–rein combinée : indications et résultats. Prog Urol 2008; 18:245-50. [DOI: 10.1016/j.purol.2007.12.013] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2007] [Accepted: 12/01/2007] [Indexed: 11/19/2022]
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13
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Margreiter R, Königsrainer A, Spechtenhauser B, Ladurner R, Pomarolli A, Hörmann C, Steurer W, Graziadei I, Vogel W. Our experience with combined liver–kidney transplantation: an update. Transplant Proc 2002; 34:2491-2. [PMID: 12270489 DOI: 10.1016/s0041-1345(02)03187-1] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Affiliation(s)
- R Margreiter
- Division of Transplant Surgery, Universitatsklinik fur Chirurgie, Innsbruck, Austria.
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14
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Rose AG, Cooper DK. Venular thrombosis is the key event in the pathogenesis of antibody-mediated cardiac rejection. Xenotransplantation 2000; 7:31-41. [PMID: 10809055 DOI: 10.1034/j.1399-3089.2000.00042.x] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
A review of the histopathologic features of serial biopsies and excised grafts of 117 experimental and clinical cardiac allografts and xenografts revealed a common sequence in the development of histopathologic changes in grafts showing antibody-mediated (hyperacute and acute vascular) rejection. Based on these observations, we propose the new concept that thrombosis of cardiac veins and venules is the initial key event in antibody-mediated rejection. This is followed by the development of congestion in the subtended venules and capillaries accompanied by interfascicular and, later, intermyocyte edema. Subsequently, focal or diffuse interstitial hemorrhage affecting the subendocardium, extending sometimes to involve the inner half of the ventricular myocardium, is observed. Antibody-mediated rejection therefore appears to be analogous to incomplete venous infarction of the heart. The observed histopathology (in which venular thrombosis plays a key role) favors a thrombogenic basis for the classical features of antibody-mediated rejection, namely edema, vascular thrombi and interstitial hemorrhage. A key role for venular thrombosis would explain the non-uniform distribution of the changes and may suggest new ways of preventing antibody-mediated xenograft rejection.
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Affiliation(s)
- A G Rose
- Department of Laboratory Medicine and Pathology, University of Minnesota and Fairview-University Medical Center, Minneapolis 55455, USA
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15
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Spechtenhauser B, Hochleitner BW, Konigsrainer A, Mair P, Hormann C, Steurer W, Vogel W, Graziadei I, Margreiter R. Combined liver-kidney transplantation: a single-center report. Transplant Proc 1999; 31:3177-80. [PMID: 10616431 DOI: 10.1016/s0041-1345(99)00776-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Affiliation(s)
- B Spechtenhauser
- Department of Transplant Surgery, Innsbruck University Hospital, Austria
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16
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Chen H, Xu D, Qi S, Busque S, Tan A, Daloze P. Induction of long-term small bowel graft survival by low-dose immunosuppression in tolerized recipient rats. Transplant Proc 1997; 29:697-8. [PMID: 9123486 DOI: 10.1016/s0041-1345(96)00422-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- H Chen
- Laboratory of Experimental Surgery, Notre-Dame Hospital, University of Montreal, Quebec, Canada
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17
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Katznelson S, Cecka JM. The liver neither protects the kidney from rejection nor improves kidney graft survival after combined liver and kidney transplantation from the same donor. Transplantation 1996; 61:1403-5. [PMID: 8629305 DOI: 10.1097/00007890-199605150-00021] [Citation(s) in RCA: 50] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
It has been proposed that the liver protects a simultaneously transplanted kidney from acute rejection. Using the United Network for Organ Sharing database, we compared the kidney allograft data from 248 combined liver and kidney transplants (LKT) with a control group comprising 206 contralateral kidney alone transplants (KAT) from the same donor. The LKT and KAT groups were identical with respect to most baseline parameters, save a greater degree of HLA matching in the KAT group. The overall 3-year graft survival rate was higher in the KAT group compared with the LKT group (80% vs 68%, P < 0.01). When these data were censored to remove death as a cause of graft loss and to minimize the matching effect, the 3-year survival rates were not statistically different (78% for KAT and 81% for LKT, P = NS). We conclude that the liver neither protects the kidney from rejection nor improves kidney allograft function or survival after LKT.
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Affiliation(s)
- S Katznelson
- Division of Nephrology, University of California, Davis, USA
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18
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Sumimoto R, Kamada N. Evidence that soluble class I antigen in donor serum induces the suppression of heart allograft rejection in rats. Immunol Lett 1990; 26:81-4. [PMID: 2276765 DOI: 10.1016/0165-2478(90)90179-t] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
The effect on heart allograft rejection in the rat of continuous slow infusion of donor MHC type serum is described. DA (RT1a) serum delayed significantly the rejection of PVG.RT1a heart grafts in PVG recipients (p less than 0.01), but did not affect survival of third-party WAG grafts. Grafts at both early and late stages of rejection were prolonged by serum infusion. Removal of soluble class I MHC antigen from DA serum by affinity chromatography on a monoclonal anti-class I antibody column completely abolished the immunosuppressive effect. The results may indicate that soluble class I antigen can act as a specific immunosuppressive agent in allograft rejection.
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Affiliation(s)
- R Sumimoto
- Department of Experimental Surgery, National Children's Medical Research Center, Tokyo, Japan
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19
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Affiliation(s)
- K H Meyer zum Büschenfelde
- I. Medizinische Klinik und Poliklinik, Johannes Gutenberg-Universität Mainz, Federal Republic of Germany
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20
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Cosman D, Kress M, Khoury G, Jay G. Tissue-specific expression of an unusual H-2 (class I)-related gene. Proc Natl Acad Sci U S A 1982; 79:4947-51. [PMID: 6956903 PMCID: PMC346802 DOI: 10.1073/pnas.79.16.4947] [Citation(s) in RCA: 87] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Sequence analysis of mouse H-2 cDNA clones has suggested the existence of an unusual class of H-2 (class I)-related antigens that, unlike the classical membrane-associated molecules, retains only the extracellular portion and is likely to be secreted. The expression of this class of H-2-related mRNA is tissue restricted; it is detectable in liver but not in brain, kidney, testis, thymus, or spleen. In the liver, its accumulation represents about one-fourth of all the H-2 (class I)-specific transcripts. This class of transcripts is present in mice of different inbred strains, but the level of expression differs markedly among them. A model is presented in which such a soluble form of the H-2 antigen would play the role of a blocking factor in maintaining peripheral inhibition of H-2 recognition. This would ensure tolerance of the H-2 molecule as a self antigen while permitting it to act as a guidance molecule for the associative recognition of viral and tumor antigens by cytotoxic T cells.
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21
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Chutná J, Hasek M, Halán V, Sladecek M. Induction of specific transplantation tolerance with blood serum in newborn and adult rats. Eur J Immunol 1977; 7:298-301. [PMID: 326563 DOI: 10.1002/eji.1830070511] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Histocompatibility (H) antigens present in the serum of rats induce a relatively high degree of neonatal transplantation tolerance in the absence of cellular chimerism. With the non-H-1 difference, which is relatively strong in the rat strain combination used, skin grafts survive permanently in some animals. With the H-1 plus non-H-1 difference, only some animals show a slight prolongation of skin graft survival, but cytotoxic antibody production is inhibited for long periods of time. In adult animals, at least with the non-H-1 difference, allograft survival is very significantly prolonged after treatment with serum alone, or in combination with hydrocortisone. The nonspecific component(s) of the serum also contributes to a prolongation of graft survival. The data suggest that blood serum is a good source of H antigens which seem to be present in a tolerogenic active form.
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Hasek M, Chutna J, Holan V, Sladecek M. Induction of transplantation tolerance using serum as antigen source. Nature 1976; 262:295-6. [PMID: 785269 DOI: 10.1038/262295a0] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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24
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Bewick M, McColl I, Ellis FG, Farrand CI, Burnett V. Short-term cadaver kidney preservation. BRITISH JOURNAL OF UROLOGY 1975; 47:501-11. [PMID: 1104037 DOI: 10.1111/j.1464-410x.1975.tb06247.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
200 consecutive human cadaver kidneys were preserved using 6 different techniques. Some attempt was made in the clinical situation to assess donor pre-treatment and postoperative specific recipient treatment to encourage immediate renal function. Provided the warm time was less than 60 min and the cold time less than 12 hours, intraarterial flushing with a crystalloid or colloid solution combined with pre-treatment of the donor and postoperative fluid load/frusemide drive to the recipient gave the best results.
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Terblanche J, Hickman R, Uys CJ. Renal transplantation in the unimmunosuppressed pig: an abnormal response. Br J Surg 1975; 62:474-9. [PMID: 1097028 DOI: 10.1002/bjs.1800620612] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
A series of 82 kidney allografts and autografts in unimmunosuppressed pigs surviving for longer than 5 days has been compared with a previously reported series of 24 unimmunosuppressed pig kidney allografts. In the previous series 40 per cent survived for longer than 20 days. In the present series only 2 per cent of 55 transplants performed in cross-bred pigs obtained from different farms survived for longer than 20 days. The major causes of death were unrelated to rejection, prinicipally gastric ulcer bleeding. In the further 16 transplants between different pure-bred animals (thereby ensuring genetic disparity) the ulcer incidence was lowered by a gastro-enterostomy, and 12 per cent survived for longer than 20 days. Histological assessment of rejection in the latter group revealed 20 per cent with minimal rejection, was considered insufficient to account for the death of the animals. Based on the evaluation of 95 unimmunosuppressed pig kidney allografts in both series, it is concluded that a wide and unpredictable range of survival time occurs. Therefore the pig kidney allograft model is an unsatisfactory model in which to study immunosuppressive régimes. Also the unimmunosuppressed pig appears to show less evidence of kidney allograft rejection than the dog, irrespective of genetic disparity. It is tentatively suggested that this might be a lesser manifestation of the unexplained phenomenon of minimal rejection of liver allografts noted in unimmunosuppressed pigs.
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Thomas FT, Wolf JS, Thomas JM, Lower RR, Hudson B, Burke S. Specific immunosuppression in cardiac allografting using antithymocyte sera and soluble transplantation antigen. Ann Thorac Surg 1974; 18:241-9. [PMID: 4607085 DOI: 10.1016/s0003-4975(10)64353-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
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Hilgert I. VARIATION IN THE TYPE OF IMMUNE RESPONSE TO MOUSE HISTOCOMPATIBILITY ANTIGENS AS THE FUNCTION OF THEIR FORM. ACTA ACUST UNITED AC 1974. [DOI: 10.1111/j.1744-313x.1974.tb00305.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Ranson JH, Rapaport FT, Ferrebee JW, Cannon FD, Adams PX, Localio SA. The influence of DL-A compatibility on the survival of hepatic allografts in unmodified mongrel dogs. Ann Surg 1974; 179:846-52. [PMID: 4599072 PMCID: PMC1355913 DOI: 10.1097/00000658-197406000-00005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Heterotopic hepatic transplantation was performed in 26 pairs of littermate and non-littermate mongrel dogs selected by serological criteria of DL-A compatibility. No immunosuppression was given. In non-littermates, 11 recipients of DL-A incompatible allografts survived 10-22 days (mean 13.4 days). Mean serum bilirubin rose by the 6th day. Three recipients of DL-A compatible allografts survived 13, 41, and 60 days, (mean 38 days). Mean serum bilirubin rose by the 8th day. In littermates, 5 recipients of DL-A incompatible allografts survived 7-12 days (mean 10.2 days) and mean serum bilirubin rose by the 6th day. Four recipients of DL-A compatible allografts from phenotypically DL-A non-identical donors survived 58, 82, 90 and 128 days (mean 89.5 days). Mean serum bilirubin rose by the 29th day. In contrast, 3 recipients of DL-A phenotypically identical allografts survived 171, 536 and over 636 days respectively, with normal mean serum bilirubin levels. The results confirm the role of the DL-A system in hepatic transplantation in mongrel dogs, and suggest that this dog population may constitute a suitable experimental model parallelling the current situation with regard to HL-A compatibility testing in outbred human subjects. The relatively long survival of DL-A compatible heterotopic hepatic allografts, compared with similar transplants of skin, kidney and heart, also suggests a need for studies of possible alteration in parameters of humoral and cellular reactivity in these recipients.
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Lindahl KF. Antisera against recognition sites. Lack of effect on the mixed leukocyte culture interaction. Eur J Immunol 1972; 2:501-4. [PMID: 4266010 DOI: 10.1002/eji.1830020606] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
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Mazzoni G, Di Martino C, Demofonti A, Valli A, Pellegrini S, Gentili B, Melis M. A comparison of portal and systemic venous drainage in porcine renal allografts. Br J Surg 1972; 59:541-4. [PMID: 4557358 DOI: 10.1002/bjs.1800590710] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Abstract
The results obtained when both kidneys were allografted in the pig are described. The experiments were performed in two groups of animals. In one group both kidneys were transplanted with portal venous drainage and in the other group caval drainage was used. Animals with portal venous drainage of the renal grafts survived for more than 4 months whereas those with caval drainage died within 15 days.
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Camiener GW, Wechter WJ. Immunosuppression--agents, procedures, speculations and prognosis. PROGRESS IN DRUG RESEARCH. FORTSCHRITTE DER ARZNEIMITTELFORSCHUNG. PROGRES DES RECHERCHES PHARMACEUTIQUES 1972; 16:67-156. [PMID: 4569508 DOI: 10.1007/978-3-0348-7081-8_2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
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Brent L. Allografts and specific unresponsiveness. N Engl J Med 1971; 284:499-500. [PMID: 5542051 DOI: 10.1056/nejm197103042840911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
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