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The First International Scientific Conference on Human Endogenous Retroviruses (HERVs) and Disease, Lyon-France, May 26-27th 2015, brought together scientific and medical specialists from around the world investigating the involvement of human endogenous retroviruses (HERVs) in complex human diseases. [ABSTRACT FROM AUTHOR] more...

Multiple sclerosis (MS) is a complex multifactorial disease of the central nervous system (CNS) for which animal models have mainly addressed downstream immunopathology but not potential inducers of autoimmunity. In the absence of a pathogen known to cause neuroinflammation in MS, Mycobacterial lysate is commonly used in the form of complete Freund's adjuvant to induce autoimmunity to myelin proteins in Experimental Allergic Encephalomyelitis (EAE), an animal model for MS. The present study demonstrates that a protein from the human endogenous retrovirus HERV-W family (MSRV-Env) can be used instead of mycobacterial lysate to induce autoimmunity and EAE in mice injected with MOG, with typical anti-myelin response and CNS lesions normally seen in this model. MSRV-Env was shown to induce proinflammatory response in human macrophage cells through TLR4 activation pathway. The present results demonstrate a similar activation of murine dendritic cells and show the ability of MSRV-Env to trigger EAE in mice. In previous studies, MSRV-Env protein was reproducibly detected in MS brain lesions within microglia and perivascular macrophages. The present results are therefore likely to provide a model for MS, in which the upstream adjuvant triggering neuroinflammation is the one detected in MS active lesions. This model now allows pre-clinical studies with therapeutic agents targeting this endogenous retroviral protein in MS. [ABSTRACT FROM AUTHOR] more...

To identify the risk factors associated with presentation for care with CD4 cell count ≤200 cells/mm3 and death in HIV-infected patients in Lyon, France. Data were analyzed on participants from mid-1992 to December 2006 in the Lyon section of the French Hospital Database on HIV Infection. Patients were stratified into two categories according to CD4 cell count at first presentation for care in University of Lyon hospitals: Group 1 (Gr1) patients with CD4 ≤200 cells/mm3 and Group 2 (Gr2) patients with CD4 >200 cells/mm3. Multivariate logistic regression assessed the risk factors associated with first presentation for care with CD4 ≤200 cells/mm3. Survival was analyzed according to the Cox regression model. Among 3569 eligible patients (838 females and 2731 males, mean age: 36.3±10.3 years), 1139 (31.9%) were categorized as Gr1. The factors associated with first presentation for care with CD4 ≤200 cells/mm3 were: older age, male gender, route of HIV transmission, migrant populations, geographical areas other than Rhône-Alpes, and access to care in 1992–1997. Overall mortality was higher in Gr1 than in Gr2 (24.4% [278/1139] vs. 4.1% [101/2430]; p<0.001). The risk of death was 5.81 [4.61–7.32] in Gr1 compared to Gr2. In addition to CD4 cell count, age and enrollment periods for care were factors independently related to death. Despite public health efforts in Lyon, one-third of HIV-infected patients reach the health care system with CD4 cell count ≤200 cells/mm3, which was linked with higher mortality. [ABSTRACT FROM PUBLISHER] more...

Ten Pneumocystis jirovecii pneumonia (PCP) cases were diagnosed in renal transplant recipients (RTRs) during a 3-year period. Nosocomial transmission from HIV-positive patients with PCP was suspected because these patients shared the same hospital building, were not isolated, and were receiving suboptimal anti-PCP prophylaxis or none. P. jirovecii organisms were typed with the multitarget polymerase chain reaction-single-strand conformation polymorphism method. Among the 45 patients with PCP hospitalized during the 3-year period, 8 RTRs and 6 HIV-infected patients may have encountered at least 1 patient with active PCP within the 3 months before the diagnosis of their own PCP episode. In six instances (five RTRs, one HIV-infected patient), the patients harbored the same P. jirovecii molecular type as that found in the encountered PCP patients. The data suggest that part of the PCP cases observed in this building, particularly those observed in RTRs, were related to nosocomial interhuman transmission. [ABSTRACT FROM AUTHOR] more...

The therapeutic field of in utero transplantation of stem cells, into human fetuses, has developed since 1988 with the hope of improved probability of engraftment and tolerance, due to immune immaturity of the host. Fifteen years later, it is possible to evaluate the results that we and others have obtained in the treatment of several fetal diseases. Seven fetal patients have been treated in Lyon: In 2 cases, pregnancy termination was induced by the in utero injection; in the 5 other cases, engraftment was obtained and repeatedly documented with presence of donor HLA antigens and/or Y chromosome in recipients. In the 2 patients with combined immunodeficiency disease, a sustained reconstitution of immunity was obtained as a result of the transplant but other complications occurred thereafter. In patients with thalassemia major, Niemann-Pick disease or hemophilia, a very partial and very transitory benefit was only obtained. Approximately 33 other patients with immunodeficiencies, hemoglobinopathies or inborn errors of metabolism have been treated worldwide, over the last 13 years, with a comparable method, using parental or fetal stem cells transplanted in utero. Successful treatment has usually been recorded in immunodeficiencies, and insufficient results have been obtained in the other cases. This form of treatment can therefore be recommended after prenatal diagnosis of combined immunodeficiency but additional research is required to improve the degree of engraftment, the lack of resistance of the host and the 'space' available for hematopoiesis in the other conditions. [ABSTRACT FROM AUTHOR] more...

Background. Renal myofibroblast infiltration has been shown to be strongly associated with renal function decline in several chronic renal diseases. The purpose of the present study was to investigate whether early detection of myofibroblast infiltration using α‐smooth‐muscle actin (α‐SMA) expression in time‐zero biopsies predicts renal allograft dysfunction. [ABSTRACT FROM PUBLISHER] more...

We used enzyme-linked immunosorbent assays (ELISA) to investigate the presence of interleukin-10 (IL-10) in the serum of patients developing post-transplant lymphomas. Serum IL-10 was detected in 14 out of 19 cases with a lymphoma or Hodgkin's disease, with higher values being observed in patients who had developed a lymphoma within the first few months post-transplantation, and who had an aggressive form of the disease. Eleven out of the 14 patients in whom IL-10 was detected had Epstein–Barr virus-positive tumors. And 11 out of 14 patients died of lymphomas. In most of the patients who had detectable IL-10 at the time of diagnosis of the lymphoma, the IL-10 had not been present previously, but it was found in the serum of 7 out of 9 dialysis patients, and in 8 out of 17 stable transplant patients. We conclude that IL-10 plays a role in the development of the more severe forms of post-transplant lymphomas, and may be secreted by tumor cells. However, data from patients with chronic renal failure or patients undergoing immunosuppressive therapy must be treated with caution. [ABSTRACT FROM AUTHOR] more...

Three human fetuses were treated by transplantation of human fetal liver stem cells. Two of them had severe immunodeficiency disease and the third had thalassaemia major. All three in-utero transplants were followed by engraftment. No adverse effect was seen. The three patients have now been born: the first is very healthy thanks to the reconstitution of cell-mediated immunity associated with this transplant, and he lives normally at home; the other two, who were treated more recently, have not yet shown a complete effect. The feasibility and efficacy of this procedure, used for the first time in humans, has therefore been demonstrated: during early fetal development, foreign cells engraft readily and may result in significant improvement of a large variety of inherited diseases. [ABSTRACT FROM AUTHOR] more...

Examines the metabolic control of type I (insulin dependent) diabetes after pancreas transplantation in Great Britain. Assessment on the correction of metabolic abnormalities in type I diabetes; Development of techniques for controlling the exocrine secretion; Characterization of insulin profiles by hyperinsulinemia. more...

The anti-Epstein—Barr virus (EBV) T cell response was studied in a severe combined immunodeficiency patient (PS) in whom stable peripheral blood chimerlsm was induced by transplantation of fetal liver stem cells from two donors. PS is characterized by a complete mismatch between the T lymphocytes, derived from the transplants, and all the other cells, including EBV B lymphocytes, of host origin. The patient's peripheral blood mononuclear cells were incubated with EBV and cultured for 1 month. In these cultures, T lymphocytes strongly inhibited the prollferation of the host EBV-infected lymphoblastoid cell line (PS-LCL) and, after expansion under repeated stimulation with PS-LCL in the presence of IL-2, they specifically inhibited the growth of host – HLA-matched LCL. In contrast, these T lymphocytes failed to recognize and to lyse EBV-infected HLA-identical targets. Lysis of PS-LCL was reduced after incubation with W6/32 or with anti-DR antibodies, suggesting a role for host HLA class I and HLA class II determinants in the lysis of the target cells. PS-HLA class I and HLA class II matched LCL were also killed. However, lymphocytes from the father or from the mother were not killed when not EBV-infected, indicating that host HLA antigens served as restricting determinants for the anti-viral T cells. [ABSTRACT FROM PUBLISHER] more...

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Objectives: To determine if the interval between the last negative and the first positive HIV test is associated with demographic characteristics of HIV seroconverters.Methods: bold>A prospective cohort of patients with HIV seroconversion enrolled in the Lyons HIV hospital database was analysed. Comparisons of demographic characteristics were performed after stratification on the duration of the interval between the last HIV negative screening test and the first HIV positive screening test, which ranged from 1 day to 24 months. Linear regression methods were used to identify the covariates associated with a negative HIV antibody test followed by a positive test.Results: Age (p = 0.54), sex (p = 0.78), heterosexual route of infection (p = 0.78), other route (p = 0.40) compared with homosexual route, and estimated year of HIV infection (p value ranged from 0.84 to 0.95) were not associated with a shorter seroconversion interval after multivariate analyses. The presence of an acute HIV illness was the only predictor of a short seroconversion interval (p = 0.006) with a reduction of 84 days of the interval when it was reported.Conclusions: No selection bias for demographic characteristics of HIV seroconverters seems associated with the length of the seroconversion interval, at least for intervals < or = 24 months. [ABSTRACT FROM AUTHOR] more...

LF 1695, a synthetic immunomodulator with a low mol. wt, has been shown to exert its activity on T-lymphocytes and macrophages. It induced T-cell differentiation of bone marrow precursor cells which acquired the expression of CD3, CD4 and/or CD8. It increased lymphocyte proliferative responses to mitogens, antigens and allogeneic cells. IL-2 production was increased in Con A-activated but not in resting lymphocytes. Added to macrophages, LF 1695 augmented IL-1 production and LTB4 synthesis but it decreased PGE secretion. Hematological reconstitution of animals, following bone marrow alteration by irradiation or chemotherapy, was accelerated. Many of the effects of this compound may result from the enhancement of interleukin production, by macrophages especially. After investigations of LF 1695 effect on HIV-infected cells, clinical trials have been initiated in AIDS and ARC patients. [ABSTRACT FROM AUTHOR] more...