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Biomedical subjects

C Pouteil-Noble

Publications and source records attributed to C Pouteil-Noble.

63 records · Page 4Linked to original sources

HLA class II antigens: structure, function, and expression in immunodeficiencies, autoimmune diseases, and allograft rejection.

The major histocompatibility complex (MHC) genes, coding for the histocompatibility leukocyte antigens (HLAs) are located on the short arm of chromosome 6. The HLA gene products are involved in many immune responses. Class I and class II molecules are composed of two subunits. Class I antigens are expressed on all cell types except red blood cells; class II molecules have a more limited distribution and are found only on certain cell types. A review of our current knowledge of the genes coding for these molecules, their biochemical analysis, and the current investigation into the three-dimensional structure of the glycoproteins will allow us to understand better how this complex system, which has been preserved in animal species throughout the evolutionary process, operates. The biologic significance of HLA class I and class II molecules in the development of an efficient immune system that permits our survival in the sea of microorganisms in which we are immersed is illustrated by the severe and lethal infections that occur when these antigens are absent. Important and interesting variations in class II antigen expression are also observed in certain autoimmune diseases. Furthermore, the role of these antigens in the allogeneic reaction of graft rejection has now been clearly identified. It has become increasingly apparent how important it is to understand the antigenic variation between organs, or even between cells within an organ, and to be able to identify the circumstances that are associated with modulation of antigen expression.

Autoimmune Diseases↗

Renal transplantation at the University of Lyon.

Over the last 23 years, progress in renal transplantation has dramatically decreased mortality and transplant failures, especially during the first years following the transplant. Further improvement in immunosuppression or in induction of specific unresponsiveness should, in the future, limit the incidence of late failures. More experience in transplantation has led to reduced frequency and severity of most complications. This has resulted in acceptance of patients with risk factors such as old age or infancy, poor vascular status, hyperimmunization, or requirement for several transplants (kidney + pancreas, kidney + heart, kidney + liver, etc.). Optimum organ procurement facilities will be required to meet the increased demand for kidney transplants. It is hoped that this need will be stabilized when late transplant failures will become infrequent, thus decreasing the requirements for retransplantation.

Blood Transfusion↗

[Clinical use of immunoglobulin titers of anti-cytomegalovirus antibodies].

The frequency and severity of CMV infections in kidney, bone marrow, heart transplant recipients, in polytransfused patients, in immunodeficiencies and in newborns with congenital or peri-natal infection prompted clinical trials of immunoglobulins (Ig) with anti-CMV activity. Among the various methods for titrating Ig of plasmatic or placental origin, polyvalent or hyperimmune, ELISA would be the most sensitive assay and the neutralizing reaction might be the better reflection of a protective effect. In kidney transplantation, two non-randomized clinical trials have suggested a curative effect in association to other treatments, especially when given early. In bone marrow transplantation, three randomized studies have shown a prophylactic effect on incidence of symptomatic infections, interstitial pneumonias due to CMV, but only in seronegative patients not treated with leucocyte transfusions. No effect was observed on the time of infection, the survival of patients, the incidence of surinfections or graft versus host disease. The prophylactic effect of anti-CMV Ig in kidney and heart transplantation as well as in newborns has still to be documented in randomized trials. The possible clinical benefit for the patients and the mode of preparation of effective anti-CMV antibodies need further investigations.

Antibodies, Viral↗

[Improving the interlaboratory variation for creatinine serum assay].

PURPOSE: To assess inter-assay variation and accuracy of blood creatinine measurements as well as the effect of the standardization of the calibration procedures on inter-assay variation. METHODS: Inter-assay variation and accuracy were assessed using 30 frozen human sera and 3 certified reference materials, which were analysed by 17 creatinine assays (colorimetric: 12, enzymatic: 4, HPLC: 1). Usual calibration procedure was compared with two common calibration procedures using either a reference material (404.1 micromol/L), or secondary sera calibrators (69, 115 et 180 micromol/L). RESULTS: Most of the commercially available methods display inaccuracy, > 10% for creatininemia < 150 micromol/L in most cases. For this concentration range, the mean creatininemia was statistically significantly different as a function of the assay used (p < 0.001). Enzymatic assays produced lower results than colorimetric ones for low creatinine levels but higher results for high creatinine levels. Assays being calibrated according to the manufacturer's recommendations, the median dispersion factor was 14% for the 20 samples between 45 and 150 micromol/L, and 8% for the 10 samples between 250 and 350 micromol/L. The calibration procedure modified inter-assay variation significantly (p < 0.001) but we gained little advantage from both common calibration procedures. A significant decrease of inter-assay variation occurred within each technical group (colorimetric or enzymatic) when a common calibration was performed using calibrators which concentration(s) was(were) close to the concentrations to be measured. CONCLUSIONS: Inter-assay variation is too high to allow prediction of glomerular filtration rate (GFR) or creatinine clearance from serum creatinine level. Our results highlight the interest of a calibration procedure using several concentrations with at least one between 90 and 150 micromol/L. The marketing of such a calibrator should be considered in order to decrease inter-assay variation in the range of creatinine levels which defines a mild chronic renal failure. Such an approach will certainly reduce inter-assay variation only within each technical group but could allow to include technical group as a co-variable in the algorithms developed for predicting GFR or creatinine clearance. A global transferability will certainly need the correlation of all types of creatinine assays versus a definitive method, whom definition remains uncertain.

Blood Chemical Analysis↗

Soluble interleukin-2 receptor (S IL-2R) in renal and pancreatic transplantation.

The monitoring of plasma soluble interleukin-2 receptor (S IL-2R) concentrations has been proposed in organ transplantation, especially to detect early manifestations of rejection. In organ transplantation, immune activation occurs in various circumstances such as rejections and infections. We performed S IL-2R determination 3 times a week in the sera of 106 patients undergoing kidney and/or pancreas transplantation. In kidney transplantation, S IL-2R was increased before the transplant. It also increased under prophylactic and especially under curative anti-rejection OKT3 or ATG therapy. In 90% cases, S IL-2R increased 2 to 4 days before creatininemia rise. In the other 10% cases, no correlation could be found with any clinical status modification. S IL-2R concentrations never increased in isolated acute tubular necrosis or in cyclosporine A (CsA) nephrotoxicity. In pancreas transplantation, the correlation between S IL-2R concentrations and possible pancreas rejection, was very poor. During cytomegalovirus (CMV) infection, only 50% patients with clinical CMV manifestations had high concentrations of S IL-2R. During Dihydroxy Propoxy Methyl Guanine (DPHG = Ganciclovir) treatment, S IL-2R still increased at the beginning, then it decreased progressively when therapy was efficient on CMV infection. The monitoring of S IL-2R concentrations may be useful in the weeks following organ transplantation provided that results are interpreted in the context of clinical and other laboratory findings, particularly with the renal function status and creatininemia.

Creatinine↗