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  • 1
    Electronic Resource
    Electronic Resource
    Azathioprine-cyclosporin A (CyA) double therapy versus CyA alone after the first rejection episode in kidney-transplanted patients under CyA (1989)
    Springer
    Transplant international 2 (1989), S. 113-116 
    Details
    ISSN: 1432-2277
    Keywords: Cyclosporin A monotherapy in kidney transplantation ; Azathioprine in kidney transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A controlled trial was carried out in 78 kidney transplant recipients under cyclosporin A (CyA) monotherapy who had experienced a first rejection episode. Thirty-nine were randomly selected to receive azathioprine (AZA; 2 mg/kg per day) in combination with CyA (group AZA+), while the others continued to receive CyA alone (group AZA−). Four of the patients in the study died; three were in group AZA+ and the cause of their deaths was cardiovascular. Graft survival rates were 97% at 6, 12, and 24 months postrejection in group AZA+ as compared to 97%, 90%, and 81%, respectively, in group AZA− (P〈0.05 at 12 and 24 months). Significantly more patients were free of rejection with the double therapy than with CyA monotherapy (75% vs 51% at 12 months;P〈0.05). In spite of the addition of a second immunosuppressive drug, the CyA dosages given and the CyA trough blood levels maintained were similar in the two groups. Serum creatinine was similar in patients with and without AZA. Infectious complications were also similar in both groups. A significant macrocytosis was the only side effect of AZA therapy. On the whole, these data show the benefit of CyA-AZA double therapy in the prevention of rejection recurrence without exposing patients to either increased risk of infection or serious side effects of AZA. Whether this double therapy should be systematically administered to all recipients or only after a first rejection episode is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02459330
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  • 2
    Electronic Resource
    Electronic Resource
    Effect of the number of pregraft blood transfusions in kidney graft recipients treated with bioreagents and cyclosporin A (1991)
    Springer
    Transplant international 4 (1991), S. 235-238 
    Details
    ISSN: 1432-2277
    Keywords: Kidney transplantation, blood transfusion ; Blood transfusion, kidney graft survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The impact of a systematic, nondonor-specific, pregraft blood transfusion (BT) protocol was evaluated retrospectively in 446 consecutive, first renal transplant recipients with regard to graft survival rate, rejection, and incidence of infectious episodes. Cyclosporin A was the maintenance immunosuppressive treatment in all patients after a 2-week course of antithymocyte globulin or anti-IL-2 monoclonal antibody. Recipients were assigned to three groups according to the number of pregraft BT (one or two, three or four, or more than four). When nonimmunological failures were excluded from the study, patients receiving three or four BT had statistically better graft survival (P〈0.02) and a lower incidence of rejection episodes (P〈0.05) than those in the other groups. There were no significant differences between the three groups in the distribution of HLA mismatching (A, B and DR), time interval between the last BT and transplantation, DR6 recipient phenotype, or nonimmunological failures. Our results show that the number of pregraft BT is an important factor in transplantation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00649110
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  • 3
    Electronic Resource
    Electronic Resource
    Assessment of immunosuppression by serum inhibition of alloreaction and measurement of cyclosporin A (CyA) serum levels in kidney graft recipients under CyA (1990)
    Springer
    Transplant international 3 (1990), S. 189-194 
    Details
    ISSN: 1432-2277
    Keywords: Immunosuppression ; cyclosporin A ; Inhibition of alloreaction ; cyclosporin A ; Cyclosporin A serum levels ; inhibition of alloreaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The immunosuppressive effect of kidney graft recipient sera was studied on T-lymphocyte alloreactive line (4H) proliferation and compared to native cyclosporin A (CyA) and CyA metabolite concentrations determined by radioimmunoassay (RIA) using specific or nonspecific monoclonal antibodies. Three clinical groups were studied: (1) patients experiencing acute renal rejection episodes (CyA-R), (2) patients experiencing CyA-dependent nephrotoxicity episodes (CyA-TOX) and (3) patients in a clinically steady state (CyA-ST), according to their therapeutic regimen i.e., monotherapy (CyA alone) or polytherapy (CyA associated with prednisolone and/or azathioprine). Regardless of the clinical state, sera of patients in polytherapy displayed more inhibitory activity than those of monotherapy patients (24% and 40% inhibition of 4H proliferation, respectively, at sera dilution of 1:2), something which was no doubt due to the inhibitory activity of prednisolone on T-lymphocyte growth. In the two therapeutic regimens, CyA-ST patient sera exhibited the lowest inhibitory activity on the 4H line (45% and 65% inhibition of 4H proliferation in mono-and polytherapy, respectively, at sera dilution of 1:2). Sera from CyA-TOX patients were highly inhibitory (74% and 86% inhibition of 4H proliferation in mono-and polytherapy, respectively, at sera dilution of 1:2), in agreement with RIA assays showing increased native circulating CyA and CyA metabolites and daily CyA intake in this group as compared to CyA-St. Surprisingly, CyA-R patient sera were no less inhibitory than those of CyA-ST patients on 4H-line, antigen-induced proliferation. This clinical group did not differ from others for CyA intake or level of circulating immunosuppressive molecules, suggesting that rejection could be associated with a state of interindividual variation in sensitivity to CyA. In addition, a polytherapeutic regimen seemed to modify CyA bioavailability in CyA-ST group patients, with a decreased CyA metabolite level as compared to their monotherapy counterparts (native CyA plus metabolite/native CyA ratio being 2.73 and 3.73, respectively). In contrast, in the CyA-R patient group, polytherapy appeared to be associated with an increase in CyA metabolite circulating levels (ratio 4.79). In view of the low inhibitory activity of CyA metabolites, this profile might lead to rejection.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00366964
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  • 4
    Electronic Resource
    Electronic Resource
    Soluble interleukin 2 receptor (Tac chain) is not a reliable marker in kidney transplant recipient monitoring (1992)
    Springer
    Transplant international 5 (1992), S. 145-150 
    Details
    ISSN: 1432-2277
    Keywords: Monitoring kidney transplantation, interleukin-2 receptor ; Interleukin-2 receptor, monitoring kidney transplantation ; Kidney transplantation, interleukin-2 receptor, monitoring
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract T lymphocyte expansion is triggered through interaction of interleukin 2 (IL-2) with its high-affinity receptor (IL-2R). This molecule is a heterodimer comprising an antigen-inducible component, the Tac chain (P55). Activation of T lymphocytes also generates a soluble form of this P55 called S-IL-2R. S-IL-2R is elevated in many T-cell-related pathologies (leukaemia, autoimmunity, etc.). In graft recipients, rejection is a result of T-cell activation by graft antigens and therefore might induce a release of S-IL-2R in the circulation; this parameter is now said to be a good indicator of rejection. We have performed a study in renal graft recipients in order to assess the usefulness of circulating S-IL-2R particularly to discriminate the origin of renal failure in cases of rejection or of cyclosporin-A (CsA)-induced nephrotoxicity. We demonstrated that there are no differences between isolated values in the clinical groups at the time of diagnosis. Variations in S-IL-2R are increased compared to steady-state periods during rejection and cytomegalovirus infections, although not in CsA toxicity episodes. However, at the individual level there are too many false-positive and false-negative results, making this parameter no more meaningful than serum creatinine levels alone or even in association (as tested in logistic discriminant analysis). In addition, it seems that the variations in S-IL-2R are patly related to renal function itself, as suggested by the correlation between S-IL-2R levels and serum creatinine levels. This association may explain the increase in S-IL-2R that can be observed without T cell activation. In conclusion, S-IL-2R may not be of major interest in discriminating between rejection of kidney and CsA-induced nephrotoxicity episodes in kidney allograft recipients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00336599
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  • 5
    Electronic Resource
    Electronic Resource
    Immune repertoire of graft-invading T cells (1990)
    Springer
    Transplant international 3 (1990), S. 176-180 
    Details
    ISSN: 1432-2277
    Keywords: T-cell repertoire ; Organ transplantation, T-cell repertoire ; Rejection, T-cell repertoire
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The immune repertoire of T lymphocytes invading human allografts is of fundamental importance both at the operational level, in order to achieve relevant matching, and at the functional level, since the unique capacity of T and B cells to specifically recognize allogeneic components restricts the origin of the signals leading to rejection by these cells. In this paper, the authors review their own work, as well as other contributions in this domain, with special reference to the frequency and function of donor-committed cells among the infiltrate and the relationship between T-cell receptor gene rearrangements and repertoire.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00355467
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  • 6
    Electronic Resource
    Electronic Resource
    A study on OX39, a murine anti-rat interleukin 2 receptor antibody (1988)
    Springer
    Transplant international 1 (1988), S. 58-63 
    Details
    ISSN: 1432-2277
    Keywords: Anti-rat R-IL2 ; IL2 binding ; Proliferation ; Allograft survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract OX39, a murine IgG1 monoclonal antibody (MoAb) that recognizes the 55 kDa alpha chain of the rat interleukin 2 receptor (R-IL2), was studied in vitro for its ability to interfere with IL2 binding and IL2-induced proliferation on rat concanavalin A (ConA) blasts and in vivo in a model of rat heart allografts. In vitro studies indicated that OX39 MoAb interacts with a single class of sites on the alpha chain of the rat R-IL2 with a high affinity (KD=0.8 nm) and competes with IL2 binding on this chain (KI=0.53 nm). In contrast, OX39 MoAb was found to be 10–20 times less efficient in competing with IL2 binding to the high-affinity R-IL2 (KI∼10 nm). It is proposed that the epitope recognized by OX39 on the alpha chain (low-affinity R-IL2) is modified on (or buried in) the high-affinity R-IL2 configuration. Accordingly, OX39 was found to be a weak inhibitor in vitro on IL2-induced proliferation and in vivo on allograft rejection. Allograft survival was unaffected by doses of OX39 of 20 and 50 μg/rat for 9 days; only a borderline effect was noted when doses as high as 250 μg/rat were used. A significant, but restricted, effect of OX39 could be further detected when combined with low doses of cyclosporine A (1.5 mg/kg), which were ineffective by themselves. Together, our data suggest that in order to be efficient in vivo, anti-R-IL2 MoAbs must bind with high affinity to epitopes involved in the high-affinity IL2 binding site.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00353820
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  • 7
    Electronic Resource
    Electronic Resource
    Monoclonal anti-IL2-receptor in organ transplantation (1989)
    Springer
    Transplant international 2 (1989), S. 46-52 
    Details
    ISSN: 1432-2277
    Keywords: IL2-receptor ; Monoclonal antibodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract So far, only monoclonal antibodies directed at functional target molecules on lymphocyte surface membrane have been proven useful in preventing or reversing allograft rejection episodes. Antibodies directed against light chain (P55) of interleukin 2 (IL2) receptor and able to interfere with IL2 binding on the IL2-receptor in its high-affinity conformation (only expressed on activated T cells) are effective in various animal models and recently in a preventive protocol in human kidney graft recipients. Thus, IL2-receptor targeting emerges as a new therapeutic strategy involving only a small pool of progenitors committed against donor antigens. Furthermore, membranous or soluble forms of P55, as indicators of the presence of alloreactive clones in the graft or at the peripheral level, may offer new tools for monitoring the rejection process.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02425973
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  • 8
    Electronic Resource
    Electronic Resource
    Frequency of mucosal HPV DNA detection (types 6/11, 16/18, 31/35/51) in skin lesions of renal transplant patients (1997)
    Springer
    Transplant international 10 (1997), S. 137-140 
    Details
    ISSN: 1432-2277
    Keywords: Key words Papillomavirus ; skin cancer ; kidney transplantation ; Kidney transplantation ; skin cancer ; papillomavirus ; Skin cancer ; papillomavirus ; kidney transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Human papillomaviruses (HPV) probably play a role in the development of skin cancer in renal transplant recipients. Since some mucosal HPV are strongly related to cervical cancer, we compared the frequency of HPV DNA detection (mucosal types 6/11, 16/18, and 31/33/51) in skin cancer of renal transplant recipients (21 lesions) with that in normal subjects without immunodeficiency (21 lesions) and studied the frequency of these same HPV in benign lesions of renal transplant recipients (34 lesions) and normal subjects (30 lesions). An in situ hybridization technique employing cold biotin probes was used. HPV DNA was not significantly (P = 0.095) more frequent in malignant skin cancer in renal transplant recipients (42.9 %) than in normal subjects (19.04 %), but was significantly more frequent in benign lesions in renal transplant recipients (32.4 %) than in controls (10 %; P 〈 0.05). These results on a limited number of skin lesions do not allow one to confirm the predominant role of mucosal HPV in the development of skin cancer in renal transplant recipients. HPV interaction with other factors related to the immunosuppressive state may play a role.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001470050027
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