Rejection Crisis Research Articles

Long-Term Survival (>25 Years) of Deceased Donor Kidney Transplant Recipients: A Single-Center Experience

IntroductionThe aim of this preliminary work is to analyze the clinical features of 52 patients with a functional transplanted kidney for >25 years (all first transplant and all deceased donor recipients) and to compare with a similar though more complete study from Hôpital Necker-Paris 2012. MethodsThe mean graft survival at 25 years is 12.7% and at 30 years is 10%. The actual mean serum creatinine concentration is 1.3 mg/L. We analyzed recipient age (mean, 35.9 years) and gender (29 men and 23 women). Donor age was 26.7 ± 10.3 years. Seven patients (13.4%) were transplanted with 1 HLA mismatch, 42.3% with 2 mismatches, and 44.2% with 3 mismatches. Mean cold ischemia time was 15.45 ± 7.7 hours. Of the recipients, 76% had immediate graft function; 38% experienced 1 acute rejection episode and 4 patients had 2 rejection crises. The initial immunosuppressive regimen was azathioprine (AZA) + prednisolone (Pred) in 14 patients, cyclosporin (CSA) + Pred in 13 patients, and CSA + AZA + Pred in 25 patients. Of these patients, 19% maintained their initial regimen, and 54% (28 patients) were very stable on a mixed CSA regimen for >25 years. ResultsWe present the major complications (diabetes, neoplasia, and hepatitis C virus positivity). ConclusionOur results in deceased donor kidney recipients for >25 years are similar to the mixed population (deceased donors and living donors) presented by the Necker group, although 54% of our patients remain on CSA immunosuppression, contradicting the idea that its use is not compatible with good long-term kidney function in transplant recipients.

Abrogation of Renal Allograft Tolerance in MGH Miniature Swine: The Role of Intra-Graft and Peripheral Factors in Long-Term Tolerance

We have previously demonstrated that long-term tolerance (LTT) of an MHC class-I mismatched renal allograft can be achieved with a short course of cyclosporine. In order to examine regulatory mechanisms underlying tolerance in this model, we assessed the contributions of factors within the graft and in the peripheral blood for their relative roles in the maintenance of stable tolerance. Twelve LTT recipients of MHC class-I mismatched primary kidneys were subjected to a treatment consisting of donor-specific transfusion followed by leukapheresis, in order to remove peripheral leukocytes, including putative regulatory T cells (Tregs). Following treatment, 2 controls were followed clinically and 10 animals had the primary graft removed and received a second, donor-MHC-matched kidney. Neither control animal showed evidence of rejection, while 8 of 10 retransplanted animals developed either rejection crisis or full rejection of the second transplant. In vitro assays confirmed that the removed leukocytes were suppressive and that CD4(+) Foxp3(+) Treg reconstitution in blood and kidney grafts correlated with return to normal renal function in animals experiencing transient rejection crises. These data indicate that components of accepted kidney grafts as well as peripheral regulatory components both contribute to the tolerogenic environment required for tolerance of MHC class-I mismatched allotransplants.

Altered Glycosylation in Donor Mice Causes Rejection of Strain-Matched Skin and Heart Grafts

Differential protein glycosylation in the donor and recipient can have profound consequences for transplanted organs, as evident in ABO-incompatible transplantation and xenotransplantation. In this study, we investigated the impact of altered fucosylation on graft acceptance by using donor mice overexpressing human α1,2-fucosyltransferase (HTF). Skin and heart grafts from HTF transgenic mice were rapidly rejected by otherwise completely matched recipients (median survival times 16 and 14 days, respectively). HTF skin transplanted onto mice lacking T and B cells induced an natural killer cell-mediated innate rejection crisis that affected 50-95% of the graft at 10-20 days. However, in the absence of adaptive immunity, the residual graft recovered and survived long-term (>100 days). Experiments using "parked" grafts or MHC class II-deficient recipients suggested that indirect rather than direct antigen presentation plays a role in HTF skin graft rejection, although the putative antigen(s) was not identified. We conclude that altered glycosylation patterns on donor tissue can trigger a powerful rejection response comprising both innate and adaptive components. This has potential implications for allotransplantation, in light of increasing recognition of the variability of the human glycome, and for xenotransplantation, where carbohydrate remodeling has been a lynchpin of donor genetic modification.

Prayer, Politics and the Trinity: Vying Models of Authority in Third–Fourth-Century Debates on Prayer and ‘Orthodoxy’

AbstractThis article presents a theory about a distinctive, but still neglected, approach to trinitarianism in the early church which was founded explicitly in demanding practices of prayer and personal transformation. The central thesis of the article is that this approach (with its characteristic appeal to Romans 8, and its Spirit-initiated prayer of an elevated or ascetic sort) was set on a course of almost inevitable tension with certain kinds of episcopal authority, and particularly with post-Nicene renditions of ‘orthodoxy’ as propositional assent. The theory is not to be confused, however, with a rather tired sociological disjunction between institution and ‘charisma’; the matter is spiritually more subtle than that, and implies vying perceptions of theological power, ‘orthodoxy’, and the nature of the ecclesial body. In this article I opt for a focus on the relation between Origen'sDe oratione(one of the finest discussions of the implications of Romans 8 for Christian contemplation), the suggested influence of Origen on early Antonite monasticism, and the still-mysterious motivations for Theophilus’ first attack on Origenism and the monks of Nitria in 399. The picture that emerges, once this distinctive prayer-based approach to the Trinity is clarified, is one of a late fourth-century crisis of simultaneous rejection, domestication and attempted assimilation of this elite spirituality of intra-divine incorporation.

Tissue and Organs Transplantation in the Republic of Kazakhstan

In modern surgery it is generally accepted that successful kidney transplantation restores the quality of life for a significant proportion of patients with terminal chronic renal failure and provides them with the medical and social rehabilitation. The first successful kidney transplantation from a asystilic donor in Kazakhstan was accomplished on April 17th, 1979. Total for this period there were more than 600 transplants of donor kidneys accomplished, 46 kidney transplantations accomplished from related donors, 7 - autotransplontation of kidney and more than 40 kidney transplantations at children aged 6 to 18 years. Survival of renal transplant during the first year now stands at 81%, while the number of acute intractable rejection crises tends to decrease and nowadays is 7.8%. In addition to clinical kidney transplantation, NSCS after A.N. Syzganov develops a direction of the heart and liver transplantation in the experiment and in the clinic. The number of patients having terminal chronic renal insufficiency in the country tends to a constant growth in 2011 over a year on renal replacement therapy there are more than 1,800 patients - 65 per 1 million of population, mortality on the transplantation waiting list is 35.4%. With the collapse of the Soviet Union and Kazakhstan gaining its sovereignty, a legislative vacuum arose; including issues of organ and tissue transplantation due to what, along with the solving medical issues, there was a need for a legislative framework for the creation of conditions of work in organ donation. As a result of profound analysis of existing precedents in the world based on the provision on the organ transplantation of the World Health Organization, the draft law regulating the transplantation of organs and tissues in Republic was developed. Code of the Republic has a chapter on “Transplantation of tissues and (or) of (parts of)” c introduced the article “Transplantation of tissues and (or) of organs (parts of organs) and the condition of their withdrawal,” which includes Paragraph: 1. Transplantation donor of organs and tissues can be a person, the corpse of man, and animal. 2. Forced withdrawal of organs and tissues and their transplantation is not allowed. 3. The order of organ and tissue transplantation from one person to another, from the corpse of a man and from animals to humans is established by the Ministry of Health. The source of donor organ for heterotopic allotransplantation in the Republic of Kazakhstan can be living or cadaveric donor, and in the case of using a living donor the legislation of the Republic allows transplantation only from the related donor, and only in public health facilities. The main criterion for a related donation is to guarantee its security and obtaining optimal renal transplant.

Donor Kidney Transplantation in the Republic of Kazakhstan

In modern surgery it is generally accepted that successful kidney transplantation restores the quality of life for a significant proportion of patients with terminal chronic renal failure and provides them with the medical and social rehabilitation. At the same time, not all patients in need can be provided with transplantation due to some limitations, one of the major constraints is the shortage of donor organs. The first successful kidney transplantation from a asystilic donor in Kazakhstan was accomplished on April 17th, 1979. Total for this period there were more than 600 transplants of donor kidneys accomplished, 46 kidney transplantations accomplished from related donors, 7 - autotransplontation of kidney and more than 40 kidney transplantations at children aged 6 to 18 years. Survival of renal transplant during the first year now stands at 81%, while the number of acute intractable rejection crises tends to decrease and nowadays is 7.8%. In addition to clinical kidney transplantation, NSCS after A.N. Syzganov develops a direction of the heart and liver transplantation in the experiment and in the clinic. The number of patients having terminal chronic renal insufficiency in the country tends to a constant growth in 2011 over a year on renal replacement therapy there are more than 1,800 patients - 65 per 1 million of population, mortality on the transplantation waiting list is 35.4%. With the collapse of the Soviet Union and Kazakhstan gaining its sovereignty, a legislative vacuum arose; including issues of organ and tissue transplantation due to what, along with the solving medical issues, there was a need for a legislative framework for the creation of conditions of work in organ donation. As a result of profound analysis of existing precedents in the world based on the provision on the organ transplantation of the World Health Organization, the draft law regulating the transplantation of organs and tissues in Republic was developed. Code of the Republic has a chapter on “Transplantation of tissues and (or) of (parts of)” c introduced the article “Transplantation of tissues and (or) of organs (parts of organs) and the condition of their withdrawal,” which includes Paragraph: 1. Transplantation donor of organs and tissues can be a person, the corpse of man, and animal. 2. Forced withdrawal of organs and tissues and their transplantation is not allowed. 3. The order of organ and tissue transplantation from one person to another, from the corpse of a man and from animals to humans is established by the Ministry of Health. Despite the experience of transplantation services of Republic there are still organizational issues. An important issue for the service of transplantation remains the strengthening of legal framework for donation. One of the important conditions for the service is solidary awareness and unity of health care workers standing at the stage of organ donation and transplantation, as well as to eliminate social tensions of the general public to service.

Development of Diagnostic Criteria of Rejection Crises in Liver Transplantation by Redox Potential Measurements

Monitoring of blood serum redox potential (RP) in patients with liver transplants was performed in the course of postoperative treatment. It was observed that abrupt RP shifts of over 25 mV corresponded to the onset of a rejection crisis or other dysfunction of the transplant in the patient. A statistically significant sample of 31 patients with liver transplants was examined, with false positive and false negative results not observed.

Development of Diagnostic Criteria of Rejection Crises in Liver Transplantation by Redox Potential Measurements

not Available.

Phenotyping of Lymphocytes Following Transplantation of Allogeneic Rat Pancreatic Islets into Streptozotocin-Diabetic Recipients*

We investigated the phenotypes of peripheral and cervical lymphocytes in allografted pancreatic islet recipients during graft rejection. Grafting 2000 pancreatic islets, obtained from LEW.1A rats, into streptozotocin-diabetic non-immunosuppressed LEW.1W rats acute rejection occurred within 7.0 +/- 0.6 days. Neither the T-cells (W3/13+), nor the T helper (W3/25+) or T-suppressor (OX-8+) lymphocytes were markedly altered during rejection crisis in peripheral or cervical lymphocytes. When using monoclonal antibodies detecting activation markers (OX-17 for class II antigens; ART-18 for interleukin-2 receptor) a significant increase of OX-17+ cells and OX-17+ T-lymphocytes could be observed in lymph node lymphocytes from 24 h after transplantation until 7 days, whereas the peripheral lymphocytes behaved inconspicuously. The results underline the uselessness of peripheral lymphocytes to monitor allogeneic destruction of minimal amounts of grafted tissue by using presently known differentiation and activation markers of lymphocytes.

Infectious Complications after Renal Allotransplantation: Differentiatative Diagnosis with Rejection Crisis and Possibilities for Prediction by Immunologic Monitoring

Infectious Complications after Renal Allotransplantation: Differentiatative Diagnosis with Rejection Crisis and Possibilities for Prediction by Immunologic Monitoring

Fatal Hepatitis After Long-Term Pulse Itraconazole Treatment for Onychomycosis

To report the occurrence of acute cytolytic hepatitis in a patient exposed to pulse itraconazole therapy for 24 weeks and provide a concise review of the literature on cases of itraconazole-induced hepatitis. A 61-year-old woman with no apparent risk factors for liver injury developed acute hepatitis one week after the final dose of a long-term course of pulse itraconazole therapy (200 mg orally twice daily, 1 wk on, 3 wk off, for 24 wk) for onychomycosis. Monitoring of liver enzymes was not performed during the treatment period. Serologic evaluations on presentation ruled out infectious diseases or other etiological factors. Liver function tests showed alanine aminotransferase 3330 U/L, aspartate aminotransferase 3250 U/L, and bilirubin 21 mg/dL. Liver function continued to deteriorate, and the patient underwent liver transplantation 17 days after admission. Her liver displayed reduced volume and there was a mild accumulation of ascitic fluid in the retroperitoneal cavity. Histologic evaluation showed massive panlobular necrosis. Complications occurred after transplantation and a rejection crisis worsened the clinical picture until the patient died about 4 months later. Use of the Naranjo probability scale showed the relationship of itraconazole therapy and the occurrence of acute hepatitis as probable. Itraconazole pulse therapy for onychomycosis appears to be at least as effective as and safer than a continuous treatment regimen, particularly from the perspective of potential liver damage. Only one case of severe symptomatic hepatitis occurring after pulse therapy with itraconazole for onychomycosis and requiring transplantation has been reported previously. In that case, as well as the one reported here, hepatitis symptoms occurred after completion of long-term treatment in patients who were asymptomatic both before and during therapy. Prolonged exposure to itraconazole, administered either continuously or intermittently, may precipitate severe and irreversible hepatotoxic events. Accordingly, careful monitoring of liver function parameters should be performed both during and after treatment when onychomycosis requires prolonged itraconazole administration, even in asymptomatic patients lacking apparent risk factors of hepatic injury.

Multitransplantation der Nieren: Operationstechnik, Ergebnisse, Komplikationen

Third renal transplants were performed in 31 patients (25 men and 3 women: mean age 33 +/- 11 years) with terminal renal failure. Surgical complications occurred in four of them. Acute rejection crises were frequent (48%). In three cases acute humoral vascular rejection led to loss of the grafted kidney. One patient died within 3 months. The proportion of functioning transplants was 83% at 3 months, 59% at 1 year and 20% at 5 years. Such factors as the concentration of panel-reactive antibodies, a history of previous acute humoral rejection crises or the timing of the previous transplant loss had no influence on the prognosis of the new graft. After a mean observation period of 35, 4 months patients whose HLA-DR antigens matched those of the donor at one or two loci had a markedly higher proportion of functioning renal transplants (69% and 64%, resp.) than patients without HLA-DR compatibility (0%; P less than 0.01). These results indicate that a third renal transplant does not carry any increased perioperative risk, and that the proportion of functioning transplants is good in the short term, though the long-term results are poor. Prolonged survival of the renal transplant can be expected only if there is an optimal HLA-DR match between donor and recipient.

Infektionen nach Nierentransplantation unter dreifacher oder vierfacher immunsuppressiver Behandlung

To determine, whether the infection rate after renal transplantation is influenced by the intensity of immunosuppressive treatment, the postoperative course of 100 consecutive renal transplantations in 64 men and 36 women (mean age 44.1 [18-72] years) was investigated prospectively. 87 patients received threefold basal immunosuppression with low-dose ciclosporin, azathioprine and prednisolone. In 13 risk patients (retransplantation and [or] high panel-reactive antibody titres), poly- or monoclonal antibodies were administered additionally to prevent rejection. Steroid-resistant rejection crises had to be treated with poly- or monoclonal antibodies in 15 patients. Postoperatively there were 10 patients with systemic infections (5 with cytomegalovirus, 4 with herpes simplex virus and 1 with Pneumocystis carinii). The infection rate with three- or fourfold immunosuppression did not differ significantly (5.4% vs. 9.1%). However, infections occurred more frequently after additional antirejection treatment with poly- or monoclonal antibodies (33%). It is concluded from these results that fourfold basal immunosuppression treatment with poly- or monoclonal antibodies is not associated with an increased risk of perioperative infections.

Soluble CD30 concentrations in ESRD patients with and without panel reactive HLA antibodies

In this retrospective study we compared accuracy of panel reactive antibodies (PRA) with serum soluble CD30 (sCD30) contents in predicting acute rejection crisis post-renal transplant. Pre-transplant sera from 115 patients were evaluated for their PRA and sCD30 concentrations. All patients received calcineurin inhibitor-based immunosuppressive therapy. Objective measurements for rejection were biopsy-proven acute rejection (AR) episodes within first six months of the transplant. Post-transplant sera of patients with AR were tested for the presence of donor-specific HLA antibodies (DSA). Overall AR rate was 16% (18/115). Patients positive for PRA and sCD30 tests were at significantly higher risk for AVR compared with those patients negative for both the tests (36% vs. 5%, p=0.01). Among negative PRA patients risk for AR was significantly elevated if they were also tested positive for sCD30 concentrations (21% vs. 5%, p=0.04). Of the 18 patients with AR, 14 were positive for sCD30, and 13 of them (93%) developed DSA post-transplant (p=0.001). These data showed that patients positive for sCD30 contents are at high risk for the development of DSA and AR post-transplant regardless of their pre-transplant PRA.

Life-supporting pig-to-baboon renal transplantation using GalT knockout donors: Benefit of cotransplanting a vascularized donor thymic graft

The use of animal organs for human transplantation could potentially alleviate the worldwide critical shortage of donor organs, and thus has stimulated investigation of novel strategies directed at making xenotransplantation applicable to the clinic. The latter will likely require overcoming barriers of rejection through strategies utilizing either immune suppression or tolerance induction, or a combination of the two. We have previously reported that vascularized donor thymic tissue grafts, transplanted either as composite thymokidneys or vascularized thymic lobe grafts, induced tolerance across fully allogeneic barriers in miniature swine. Recently, we have applied the strategy of vascularized thymic lobe transplantation in a model of hDAF pig-to-baboon xenotransplantation and demonstrated that these grafts induced donor-specific unresponsiveness for up to 2 to 3 months following transplantation, at which time the grafts were lost from apparent humoral rejection. We have now extended these studies using cloned α-1,3-galactosyltransferase (GalT) knockout pigs as donors. We report here our initial experience in a preclinical model of pig-to-baboon xenotransplantation. This abstract presents clinical data on recipients of GalT knockout kidneys, especially focusing on four long-term recipients of GalT knockout kidney plus thymus transplantation in detail. Briefly, these four baboons receiving either xeno-thymokidneys or vascularized thymic lobe plus kidney maintained longer than 2 months. Three of four long-term survivors maintained normal plasma creatinine levels for 56, 68, and 83 days, respectively, before expiring from unexpected causes (anesthetic complication during surgery to replace an infected intravenous catheter (day 68), and myocardial infarction, possibly drug-induced on days 56 and an arterial catheter trouble on day 83. Cytotoxic T-lymphocyte assays on day 78 in one long-term acceptor showed that the baboon maintained anti-allo cytotoxic T-lymphocyte responses but lost antipig cyctotoxic T-lymphocyte responses, indicating donor-specific unresponsiveness. The fourth baboon experienced an apparent rejection crisis between days 53 and 65, which reversed with anti-T-cell rejection therapy; subsequently the animal expired on day 81 from pneumonia. Neither hyperacute nor accelerated acute rejection was observed in any animal. Use of GalT knockout donors markedly extends the survival of vascularized thymus plus renal xenografts in baboons. Although the induction regimen still needs to be modified to reduce complications, these initial results are encouraging with regard to the potential of cotransplanting vascularized thymic tissue with organ xenografts as a means of achieving long-term tolerance across pig-to-primate barriers.

Gene Expression of Perforin by Peripheral Blood Lymphocytes as a Marker of Acute Rejection

Background: Previous findings have demonstrated that the expression of cytotoxic effector molecules is increased in acute rejection of renal allografts. In the present study, we serially examined the gene expression of perforin, granzyme B and Fas ligand (FasL) in peripheral blood lymphocytes (PBLs) of renal allograft recipients to assess the potential of their expression as a marker of acute rejection. Methods: PBLs were isolated from blood samples taken on days 2, 4, 6, 8, 10 and 12 after transplantation. Competitive PCR was performed to evaluate the abundance of mRNA of perforin, granzyme B and FasL. The mean value + 2 SD of each molecule in the control group was set as a discriminatory level for that particular molecule. Results: When all measured samples were compared, perforin expression was significantly higher in patients with acute rejection than in the control group (1.84 ± 3.01 vs. 0.71 ± 0.48, p = 0.01). The percentage of perforin expression exceeding the discriminatory level was also significantly higher in patients with acute rejection (p = 0.0003). Five patients in the rejection group (5/7, 71.4%) showed perforin expression exceeding the discriminatory level, while only 1 patient in the control group did so (1/8, 12.5%) (p = 0.02). Perforin expressions of days 0 and 1 of rejection crisis were the highest over the study period. No consistent pattern of granzyme B and FasL expression was identified in relation to rejection crisis. Conclusion: Gene expression of perforin by PBLs was upregulated in accordance with acute rejection, thus offering the possibility that it may be utilized as a marker of acute rejection.

Improvement in long-term graft survival in cadaveric renal transplant recipients treated with mycophenolate mofetil

Abstract Though mycophenolate mofetil has markedly reduced the incidence of acute rejection in renal transplantation, a significant improvement in graft survival has been more difficult to demonstrate. This retrospective study compares an historical control group of 210 consecutive renal transplant patients, who had received ATG induction associated with cyclosporin, prednisolone and azathioprine, with 187 patients receiving mycophenolate instead of azathioprine. The incidence of acute rejection was decreased with mycophenolate. In rejection-free patients, the 3-year graft survival rates were equivalent. In contrast, graft survival at 3 years improved significantly for patients who experienced a rejection crisis and remained under the initial triple drug regimen with mycophenolate compared to the patients of the historical group who were kept on azathioprine after a rejection episode. In conclusion, mycophenolate mofetil is not only able to reduce the incidence of acute rejection but could also improve the prognostic significance of acute rejection crises.

Cellular diagnostics: A challenge for laboratory medicine

Investigating cells for genetic features, malignant transformation, surface characteristics, metabolic functions and signaling will be future key elements for diagnosis of diseases. Integrating this new area into Laboratory Medicine will add new competence and responsibility to Clinical Biochemistry and Laboratory Medicine. Cellular genetics will be a main area for the diagnostic laboratory to investigate risk and prognosis for diseases having also impact on a more individualized medication. With the introduction of flow cytometry a more objective way of cell identification by immunophenotyping was added to classical microscopy allowing accurate classification of leukaemias. In addition the functional status and the origin of blood cells or cells in other body fluids (liquor, ascites) can now easily be detected. Cell mediated immunity plays an important role in infectious diseases and in transplantation medicine. The CD4/CD8 ratio of T-lymphocytes is already a routine test for differentiation between viral infection and rejection crises and for monitoring of these conditions. In cellular coagulation platelet function tests will add value to the established plasma tests. The dosage of drugs is now monitored by measuring the blood levels of drugs or their metabolites. In addition investigating the direct effect of drugs on targeted cell functions might be a more specific way.

The effect of donor gender on graft survival.

Differences in actuarial graft survival according to donor gender have been reported for renal allografts and for cardiac and hepatic allografts, but for the latter in small series with limited biostatistical power. Using the large database of the Collaborative Transplant Study (CTS), this study is an evaluation of graft survival according to donor and recipient gender for renal (n = 124,911), cardiac (n = 25,432), and hepatic (n = 16,410) transplants. Confounders, such as calendar year, geographical area, race, donor and recipient age, HLA mismatch, cold ischemia time, and others, as well as interaction terms were taken into consideration. Death-censored actuarial renal allograft survival from female compared with male donors was less in female recipients and even more so in male recipients. The donor gender-associated risk ratio for graft loss was 1.15 in female recipients and 1.22 in male recipients. The age-gender interaction term was statistically significant, the gender effect being more pronounced for younger (16 to 45 yr) compared with older (>45 yr) donors. Serum creatinine concentrations 1 yr after transplantation were also higher for recipients with kidney grafts coming from female donors irrespective of recipient gender. For first cardiac transplants, graft survival was inferior when the donor was female and the recipient male, but no statistical difference according to donor gender was demonstrable in female recipients. For first hepatic transplants overall, no significant differences according to donor gender were noted. The proportion of recipients who had treatment for rejection crisis during the first year was higher for male recipients of kidneys from female donors compared with male donors. No difference according to donor gender was demonstrable in female recipients. For cardiac and hepatic grafts, no significant effect of donor gender on the proportion of patients treated for rejection episodes was noted. The data show that adverse effects of female donor gender for different organs is much less uniform than reported in the past. An important confounder is donor age. A gender effect on graft survival is also observed for cardiac allografts. Therefore, in addition to potential "nephron underdosing," further pathomechanisms must play a role, possibly differences in immunogenicity according to donor gender.

Cultures of Kidney Transplant Fine-Needle Aspiration Samples from Rejection-Free Patients Produce a Specific Antidonor Response Suppressive Factor

Background/Aims: Growth of T cell lines from kidney graft biopsy specimens that suppress the antidonor response, either directly or through a soluble factor, both specific and nonspecific to donor, has been reported. Fine-needle aspiration biopsy sample cultures synthesize a large array of cytokines/chemokines with significant differences between stable versus acute rejection transplants. We hypothesize that the products of such cultures may be endowed with antidonor response modulation abilities in kidney transplantation. Methods: From 46 patients, 21 rejection free (group A) and 25 developing 28 acute rejection crises (group B), samples were obtained on days 7 and 30 after transplantation in group A and on day 7 and on acute rejection day in group B. The supernatants obtained after 48 h of culture were studied for IL-1 receptor antagonist, IL-4, IL-4 soluble receptor alpha, IL-12, IL-13, IFN-γ, TGF-β1, TGF-β2, GM-CSF, and PGE₂ and for their effects on mixed lymphocyte reactions, donor-recipient and recipient-third-party combinations. At the end, analysis by flow cytometry of donor-recipient cultures complemented the analysis done before cultures. Results: Day 7 supernatants from group A specifically and significantly inhibited the antidonor response; supernatants from group B nonspecifically stimulated the antidonor response. The IL-1 receptor antagonist production was significantly higher by day 7 in group A, and the PGE₂ production was significantly higher in group B. Flow cytometry analysis did not disclose significant differences between inhibited versus stimulated antidonor responses. Conclusions: Cultures of aspiration biopsy samples done early after transplantation in rejection-free patients produce soluble suppression-specific antidonor response factor(s), not present in cultures from biopsy specimens taken before and during rejection. This was associated with IL-1 receptor antagonist synthesis.