Remisión de enfermedad severa por citomegalovirus y enfermedad linfoproliferativa post-trasplante en un receptor de trasplante renal tras terapia con ganciclovir y cambio en la medicación inmunosupresora / Remission of severe disease induced by cmv and lymphoproliferative posttransplant disease after changing the immunosuppression regime

Se describe el caso de un receptor de trasplante renal con sobreinmunosupresión inducida por la interacción de tacrolimus y fluconazol que desarrolló dos enfermedades severas producidas por dos virus diferentes del grupo herpes: enfermedad por citomegalovirus (CMV) y enfermedad linfoproliferativa post-trasplante (ELPT). La detección del genoma del virus de Epstein-Barr (VEB) en sangre periférica precede al diagnóstico de ELPT. Ambas enfermedades remitieron con el cambio del régimen inmunosupresor y tratamiento con ganciclovir. Debido a que la infección por CMV es un factor de riesgo para desarrollar ELPT y a que las manifestaciones clínicas y endoscópicas de ambas enfermedades pueden confundirse, en los pacientes con enfermedad por CMV se debe descartar la presencia de una ELPT concomitante, sobre todo si estos pacientes son seronegativos para el virus de Epstein-Barr. La detección del genoma del VEB en sangre periférica puede ser de gran ayuda en el diagnóstico precoz de ELPT en estos pacientes. (AU)

[Remission of severe disease induced by CMV and lymphoproliferative post-transplant disease after changing the immunosuppressive regime]. / Remisión de enfermedad severa por citomegalovirus y enfermedad linfoproliferativa post-trasplante en un receptor de trasplante renal tras terapia con ganciclovir y cambio en la medicación inmunosupresora.

We describe a renal transplant recipient, with overimmunosuppression induced by the interaction of tacrolimus and fluconazole, who developed two severe diseases produced by two different viruses of the herpes group (cytomegalovirus [CMV] disease and posttransplant lymphoproliferative [PTLD] disease EBV-related). Detection of Epstein-Barr virus (EBV) DNA in the blood preceded the histological diagnosis of PTLD. Both diseases improved after changes in the immunosuppressive regime and treatment with ganciclovir. Because CMV infection is a risk factor in developing PTLD, and the clinical and endoscopic manifestations of both diseases could be become confused, PTLD should be excluded in EBV seronegative patients that develop CMV disease. The detection of the EBV genome in blood could help in the early diagnosis of PTLD in these patients.

Visceral leishmaniasis and other severe infections in an adult patient with p47-phox-deficient chronic granulomatous disease.

We report a rare case of a male patient without known immunodeficiency consecutively diagnosed with visceral leishmaniasis, brain abscess and cavitating pneumonia in the 3rd decade of life. Chronic granulomatous disease (CGD) was diagnosed by a nitroblue tetrazolium test. A p47-phox mutation of the NADPH oxidase of the leukocytes was suspected by immunoblotting and confirmed by DNA analysis. The patient was homozygous for this mutation while his mother and sister were heterozygous asymptomatic carriers. After the CGD diagnosis the patient started a chronic prophylactic regimen with subcutaneous interferon-gamma (0.05 mg/m2 of body surface/three times a week), and oral trimethoprim-sulfamethoxazole and itraconazole (both at 5 mg/kg/day) with no subsequent infections after 12 months of follow-up.

Cytomegaloviraemia and T cell subpopulations in renal transplant patients.

We studied 54 consecutive recipients of renal transplants to evaluate their immunological responses to cytomegalovirus (CMV) infection. Forty-three (79.6%) patients developed CMV infection, and all of them subsequently recovered. Fourteen of these infected patients (32.6%) developed viraemia during the infectious process, four of whom then manifested the disease. The number of lymphocytes and their main subpopulations was normal before the appearance of CMV infection. During the infection there was a significant growth (P < 0.001) in the CD8+DR+ subset, corresponding to activated T suppressor/cytotoxic lymphocytes, whereas the natural killer measured subsets remained within normal limits during the whole infectious process. As all viraemic patients recovering from the infection developed CD8+DR+ activation, we conclude that this recovery is associated with the immunological activation.

Detection of an HLA-DPw1-associated epitope by an alloreactive T cell clone.

An alloreactive T cell clone was generated using HLA-A, B, C, DR, DQ, D identical, but HLA-DP different homozygous typing cells as responder and stimulator. The alloproliferative and -cytotoxic clone appears to recognize an epitope associated with HLA-DPw1.

MHC class II restricted self-recognition after allostimulation: clonal analysis.

After allostimulation in vitro using a combination of HLA-A, B, C, DR, DQ, D identical but HLA-DP different homozygous typing cells, 34 T cell clones were derived. Thirty-one of them were alloreactive clones, but three clones were found to be autoreactive. One of these autoreactive clones was further expanded. In order to characterize in more detail the determinant restricting the autologous response, a panel of HLA-typed peripheral blood mononuclear cells (PBMC) or Epstein-Barr virus lymphoblastoid cell lines (EVB-LCL) was typed. A good correlation of typing responses with the self haplotype HLA-A1, B8, Cw7, DR3, DRw52, DQw2 was found. Typing responses also segregated together with this haplotype in informative families. Blocking studies using MHC class I and II specific monoclonal antibodies (MoAb) linked the restricting determinant to MHC class II molecules. The clone which was both autoproliferative and autocytotoxic bore the CD3(+), CD4(+), CD8(-), Ia(+) phenotype. Antibiotics or foreign plasma proteins were ruled out as restricted determinants.

T cell dependence of human IgE response: quantitative and functional studies.

In 108 allergic and nonallergic patients T3, T4 and T8 cells were quantified. No significant differences were found when comparing healthy and allergic individuals. Functionally, the role of T8 suppressor and cytotoxic population was studied by removing this subset, comparing the IgE produced in vitro by peripheral blood lymphocytes of unfractionated and T8-depleted cultures. Results indicate a statistically significant increase of the in vitro IgE production when cultures from healthy people and 'normoproducer' allergics (in vitro spontaneous IgE production no more than 900 pg/ml/10(7) cells) were depleted of T8 cells. The same experiments in 'hyperproducer' allergics (in vitro spontaneous IgE production more than 900 pg/ml/10(7) cells) show no significant difference in the IgE production when T8 cells were depleted.

Transmethylation reactions in human basophils induced by anti-IgE or specific antigen.

The activation of methyl transferases in the membrane of human basophilic leukocytes was measured by incorporation of 3H-methyl groups into phospholipids. Basophils of healthy individuals were activated by anti-IgE, those of pollen allergic patients by the specific antigen, Lolium perenne extract. Basophil-rich fraction was obtained from peripheral blood by centrifugation in a gradient of Ficoll/metrizamide (g = 1.085). After incubation with anti-IgE an increase in the 3H-methyl incorporation was detected during the first 30 s of the reaction. The maximal incorporation in basophils of the pollen allergic patients, activated by L. perenne extract, was enhanced at 15 s. Appropriate controls showed that the activation of methyl transferases occurred in basophils only.

Fractionation and biological characterization of Olea europea pollen extract.

Preliminary fractionation of Olea european pollen extract has been performed. At least 10 antigenic fractions have been found by crossed electrophoresis. After Sephadex gel filtration, two fractions with a molecular weight of 160,000 and 65,000 have been obtained. The fractions were evaluated for allergenic activity by two in vitro techniques: polystyrene tube radioimmunoassay (PTRIA) and basophil degranulation test (BDT), and by skin tests. All tests indicated that the most reactive fractions were those in the 65,000 molecular weight peak. BDT has been shown to be a very reliable method as compared with histamine release and other parameters. Although common antigenic fractions have been found for Lollium perenne and O. europea, no cross-allergenicity has been shown by PTRIA inhibition.

Role of T gamma cells in the in vitro IgE response after antigenic stimulation.

Fifteen patients with seasonal allergic pollenosis and five controls were investigated to elucidate the role of the T gamma-cell population in the in vitro IgE response by peripheral blood lymphocytes (PBL). In vitro IgE production by PBL of atopic patients after antigenic stimulation was measured in culture supernatants. The optimal dose for antigenic stimulation was found to be 0.16 micrograms/20 X 10(6) cells of purified antigen. No difference was found when comparing the percentages of T cells (E rosettes) between the two groups: mean per cent for controls was 69.2 +/- 5.76 versus 69.54 +/- 4.42 for the allergic group. With regard to the T gamma-cell population, the values obtained by rosetting with ox erythrocytes sensitized with IgG antibody were 12 +/- 0.71% in normals and 9.8 +/- 1.32% in those with allergic pollenosis. This difference, although significant, may not be enough to explain the different pattern when the in vitro IgE production of both groups investigated was compared. In order to detect the role of T gamma cells in this system, lymphocyte cultures, depleted of T gamma cells, were performed and compared with unfractionated cultures from the same donors. Our results show no differences in the in vitro IgE production when T gamma cells were depleted as compared with the unfractionated cultures.