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Biomedical subjects

M López-Hoyos

Publications and source records attributed to M López-Hoyos.

At least 19 recordsLinked to original sources
PubMed2006

Calcineurin inhibitors affect circulating regulatory T cells in stable renal transplant recipients.

INTRODUCTION: Immunosuppression, although crucial for short-term management, has been described in renal transplantation to be a major hurdle for long-term graft survival. Efforts have been directed at achieving a true state of allotolerance, thereby reducing the load of immunosuppression. Recently, increased frequencies of CD4(+)CD25(high) regulatory T cells (Tregs) have been described as an additional mechanism to induce alloimmune tolerance. MATERIALS AND METHODS: We assessed 64 renal transplant recipients with stable renal function for at least 1 year, divided into two groups: one composed of patients receiving rapamycin but not calcineurin inhibitors (CNIs), and another, of those receiving CNIs but not rapamycin. RESULTS: We demonstrated that T cells with a regulatory phenotype were decreased in peripheral blood of renal transplant recipients under CNI therapy compared to those who were CNI-free. The Tregs in our patients showed a modest association with renal function as measured by the delta serum creatinine, which was not significant. CONCLUSIONS: CNIs, but not rapamycin, reduce the frequencies of circulating Tregs in renal transplant recipients. The use of rapamycin might be further exploited in strategies reducing immunosuppression in renal transplantation. Furthermore, quantification of blood Tregs may be a suitable tool to identify those recipients who are candidates for reducing immunosuppression.

Adult↗
PubMed2006

[Autoimmune pancreatitis. An infrequent or underdiagnosed entity? Pathological, clinical and immunological characteristics].

In the last few years, reports of pancreatic inflammatory diseases caused by immunological mechanisms and with good response to steroid treatment have increased. Although this entity has been known by a number of names, at present the most widely accepted is that of autoimmune chronic pancreatitis (ACP). The present report describes the clinical, immunological, morphological, functional and pathological characteristics of two patients recently studied at our unit and discusses currently used diagnostic tests. The two patients had a complete response to steroid therapy. In our opinion, ACP is probably underdiagnosed in Spain. The availability of morphological, pathological and serological diagnostic tools developed in recent years will help to precisely determine the epidemiology of this process. Thus, quantification of serum levels of anti-carbonic anhydrase II and IgG4 has greatly contributed to the diagnosis of ACP. These tests should be performed in patients with a possible diagnosis of ACP, those suffering from diabetes mellitus type I with impairment of exocrine function, and those with alcoholic pancreatitis and a poor response to alcohol elimination. Once we are able to diagnose and determine the real prevalence of ACP in our setting, the most appropriate therapy and prognosis of this disease can be established.

Aged↗
PubMed2005

Clinical significance of antiphospholipid antibodies on allograft and patient outcome after kidney transplantation.

INTRODUCTION: Antiphospholipid antibodies (APA) have acquired great relevance as atherogenic factors. Kidney graft recipients have a higher prevalence of cardiovascular disease (CVD) than the general population, which is not fully explained by the classical vascular risk factors. The aim of this study was to assess the influence of APA on kidney graft and patient outcomes with special focus on CVD. MATERIALS AND METHODS: One hundred ninety seven cadaveric kidney graft recipients with functioning grafts for more than 1 year underwent determination of serum APA titres (anti-cardiolipin and anti-beta-2 glycoprotein I IgG and IgM antibodies) in one pretransplant serum and in second one obtained at least 1 year after transplantation. In the case of postransplant CVD, the postransplant serum was always chosen before the cardiovascular event. The enzyme linked immunosorbent assay (ELISA) for anti-cardiolipin antibodies was performed in the presence of cofactor. RESULTS: Twenty-seven percent of patients had pretransplant APA, whereas 15.7% developed postransplant APA de novo. The presence of pretransplant serum APA was not associated with a higher risk of postransplant CVD. The development of postransplant APA de novo showed a relationship to an acute rejection episode (ARE): the frequency of patients who had APA de novo was higher among patients who suffered ARE (18.8% vs 7%, P = .01). In addition, in patients who suffered any ARE, the production of postransplant APA was associated with a higher frequency of postransplant CVD. CONCLUSIONS: The detection of APA is not an independent risk factor for CVD after kidney transplantation. The inflammatory phenomena secondary to an ARE may be responsible for the de novo production of postransplant APA, which may be associated with the development of postransplant CVD. The control of cardiovascular risk factors should be intensified in this special group of patients.

Antibodies, Antiphospholipid↗
PubMed2005

Impact of HLA antibodies on transplant glomerulopathy.

The influence of humoral rejection on the development of chronic allograft nephropathy (CAN) is controversial, especially in relation to transplant glomerulopathy. The aim of our study was to analyse the influence of anti-HLA antibodies on the development of transplant glomerulopathy (cg0, cg1, cg2, and cg3; Banff'97). We selected all renal transplants patients from 1975 to 2003 who had a functioning graft for at least 6 months and a clinically indicated graft biopsy with CAN and chronic glomerular changes (case group). We studied the presence of anti-HLA antibodies (Ab) in the last serum taken while the graft was functioning and divided them into three groups according to the severity of glomerular lesions. We also selected 52 contemporary and comparable cases without transplant glomerulopathy (control group). A total of 77 case had transplant glomerulopathy: 39 cg1, 29 cg2, and 9 cg3. Pretransplant Ab titers and number of previous blood transfusions were higher among the subgroup with the most severe glomerulopathy. Patients who developed posttransplant anti-HLA Ab more frequently showed transplant glomerulopathy. Serum creatinine and proteinuria were higher among cases with chronic glomerulopathy, and more grafts were lost in that group. Thus, the presence of HLA-Ab is a key factor in the development of transplant glomerulopathy and chronic allograft rejection.

Follow-Up Studies↗
PubMed2005

Clinical disease activity and titers of anti-dsDNA antibodies measured by an automated immunofluorescence assay in patients with systemic lupus erythematosus.

Autoantibodies specific for double stranded DNA (anti-dsDNA Abs) are a serological biomarker of systemic lupus erythematosus (SLE) and constitute useful tools for monitoring many SLE patients. A new automated immunofluorescence and quantitative assay (EliA dsDNA) has recently become available. Its performance has been demonstrated to be equivalent to the Farr and Crithidia luciliae fluorescence (CLIFT) tests. The aim of the present work was to assess the utility of this new assay to monitor clinical activity in a large cohort of SLE patients. To this end, 1020 sera from 181 SLE patients were evaluated by the two methods. Results showed a higher frequency of positive results of anti-dsDNA Abs during lupus flares measured by EliA dsDNA than by CLIFT. Likewise, titers of those Abs were significantly increased in active SLE in comparison with inactive SLE when measured by EliA dsDNA but not by CLIFT. Serum titers of anti-dsDNA Abs by both assays showed a significant negative association with concentrations of C3 and C4. In summary, this retrospective study on a large cohort of patients demonstrated that EliA dsDNA was at least as useful as CLIFT as monitoring tool in the follow-up of SLE patients, but with the advantages of being automated, quick and quantitative.

Adolescent↗
PubMed2005

[The immunological barrier in renal transplantation from living donor].

Living donor kidney transplantation is uncommon in our country, mostly due to the high rate of cadaveric donation. However, such a rate has been held back in recent years and it is thought that there will be great problems in organ shortage in the next years, especially for young patients. Thus, living donation seems to be an alternative. Such a practice is particularly useful in hypersensitized patients with positive crossmatch and in ABO incompatibility. In these two cases, the waiting time for kidney transplantation goes on for many years. With the development of desensitizing protocols that employ high-dose intravenous immunoglobulins and/or plasmapheresis, together with the use of more sensitive and objective assays for immunological monitoring, patients that were not candidates for kidney transplantation in the past are now being transplanted. In the present work, immunological factors that participate in living kidney transplantation are revised, with special focus on hypersensitized patients. Available data show that living donation is a feasible alternative for future, once all the ethical problems have been solved.

Adult↗
PubMed2001

Limited immune reconstitution at intermediate stages of HIV-1 infection during one year of highly active antiretroviral therapy in antiretroviral-naive versus non-naive adults.

Although several reports have attributed the clinical benefits of highly active antiretroviral therapy (HAART) to a possible immune restoration, long-term data are still scarce and most derive from patients with either advanced or very early stages of HIV infection. In the present study, changes in lymphocyte subsets, activation markers, and adhesion molecules in CD4+ and CD8+ lymphocytes were carefully monitored over a 1-year period in 27 HIV-infected adults at an intermediate stage of HIV infection. Cytokine-producing patterns were also studied. In these patients the HIV viral load disappeared by month 4 of HAART. Only limited immunological changes were observed: an incomplete recovery of naive CD4+ T cells, a less activated state of CD8+ T cells, and a repopulation of IL-2- and IFN-gamma-producing CD4+ T cells. These changes were observed principally in patients with more advanced disease. Furthermore, HIV-infected subjects who had received HAART previously showed less marked immunological changes than antiretroviral-naive individuals. In conclusion, the sustained viral suppression during 1 year of HAART was accompanied by limited immunological recovery at intermediate stages of HIV infection. This finding indicates a need for longer HIV suppression in order to achieve effective recovery of the immune system.

ADP-ribosyl Cyclase↗
PubMed2001

Impaired type-1 activity and increased NK cells in Gleich's syndrome.

BACKGROUND: An altered production of cytokines has been described in Gleich's syndrome. Our aim was to study the cytokine production at the single-cell level in a patient with Gleich's syndrome and to determine whether it changed during a flare episode. METHODS: Blood samples were obtained from a 30-year-old woman diagnosed with Gleich's syndrome before and during the subsequent flare of edema of trunk and arms and weight gain. The major lymphoid subsets (CD4+, CD8+, and CD19+) and natural killer (NK) cells were measured by flow cytometry. Cytokine-producing T cells (IL-2, IFN-gamma, and IL-4) were quantified in whole blood by intracellular staining with specific monoclonal antibodies and flow cytometry analysis after polyclonal stimulation with phorbol 12-myristate 13-acetate and ionomycin. RESULTS: Increased numbers of immature CD4+CD8+ T cells and NK cells were observed in peripheral blood during the asymptomatic period. The latter population significantly decreased during the flare. Type-1 cells were decreased in both asymptomatic and, more markedly, during the attack with respect to healthy subjects. CONCLUSIONS: The decreased type-1 response demonstrated in this patient might be the basis of the hypereosinophilia of Gleich's syndrome. Besides, the NK cells might play a role in the pathogenesis of these inflammatory episodes.

Adult↗
PubMed2000

Circulating levels of matrix metalloproteinases MMP-3 and MMP-2 in renal transplant recipients with chronic transplant nephropathy.

BACKGROUND: Chronic transplant nephropathy remains the major cause of graft loss after the first year post transplant, with the exception of death with functioning graft. The histological hallmark of chronic kidney rejection is progressive fibrosis in which extracellular matrix turnover plays an important role. This turnover is regulated by several systems of connective tissue proteases, the matrix metalloproteinases family being one of them. Every metalloproteinase exerts a different function over extracellular matrix proteins and can contribute to the pathogenesis of several diseases, such as rheumatoid arthritis and glomerulonephritis. The role of metalloproteinases in the pathogenesis of chronic transplant nephropathy and in kidney transplantation has not yet been addressed. METHODS: We measured the serum levels of proMMP-1, proMMP-2 and proMMP-3 by ELISA in 40 patients with chronic transplant nephropathy, 30 with acute rejection, 30 with stable graft function for a time equivalent to chronic transplant nephropathy, 30 with stable graft function for a time equivalent to acute rejection, and 30 healthy age-paired blood donors. RESULTS: Serum proMMP-2 and proMMP-3 were significantly higher in patients with chronic transplant nephropathy than in patients with acute rejection, stable graft function and healthy donors. The most striking finding was the significant positive correlation observed between serum levels of proMMP-3 and serum creatinine, and between circulating levels of proMMP-2 and proteinuria. Serum concentration of proMMP-1 was increased in patients with acute rejection compared with those with stable graft function and healthy donors. CONCLUSIONS: Serum proMMP-2 and proMMP-3 reflect the changes of glomerular and interstitial extracellular matrix in chronic transplant nephropathy, suggesting that they could play a role in the pathogenesis of this condition. Acute rejection is associated with increased levels of proMMP-1, which could be a reflection of the stimulation induced by a number of inflammatory cytokines produced in such a process.

Acute Disease↗
PubMed2000

B lymphopenia in uremia is related to an accelerated in vitro apoptosis and dysregulation of Bcl-2.

BACKGROUND: Lymphopenia has been described in patients with chronic renal failure (CRF). It is postulated that the decline in lymphocytes is due to accelerated apoptosis. We investigated whether dysregulation of programmed cell death plays a role in the immunodeficiency described in CRF. METHODS: Peripheral blood lymphocytes (PBL) from pre-dialysis uraemic patients (nHD) and haemodialysed patients (HD) were cultured with no stimulus for 96 h. Apoptosis of lymphocytes was measured by propidium iodide staining and flow cytometry. Expression of Fas and Bcl-2 was also analysed by flow cytometry. RESULTS: Peripheral blood B cells were significantly lower in pre-dialysis and haemodialysis uraemic patients compared to control. Lymphocytes from both groups of patients had a higher rate of apoptosis in vitro than those from healthy controls. This effect was more pronounced in B lymphocytes and a significant correlation between the B lymphopenia and the percentage of apoptotic B cells after 48 h of culture without stimulus was observed. The increased lymphocyte apoptosis in CRF was accompanied by a significantly lower in vitro Bcl-2 expression. However, Fas did not seem to play a role in spontaneous lymphocyte apoptosis in end-stage renal disease. CONCLUSIONS: Our data indicate that B lymphopenia in CRF may be partially attributed to an increased susceptibility to cell death by apoptosis that is associated with a decreased expression of Bcl-2.

Adolescent↗
PubMed1999

Differences in anti-CREG antibody formation between transplanted and nontransplanted renal patients.

BACKGROUND: The aim of this study was investigation of the HLA-I cross-reactive group (CREG)-specific antibodies (Abs) in sera from patients with a failed renal transplant and from nontransplanted patients. METHODS: A total of 5292 sera from 570 patients awaiting kidney transplantation were screened for the presence of HLA-I CREG-specific Abs. Patients who had never received a transplant (group A), and those with a previous transplant and Abs either not related (group B) or related to donor specificities (group C) were studied. A further division was made for Abs directed against specificities either included in (intra-CREG) or not included in patients' HLA-CREG (extra-CREG). RESULTS: Twelve of 24 (50%) Abs produced in response to mismatched donor HLA specificities after a failed graft were intra-CREG Abs, compared to 7 of 39 (18%) Abs that were not transplant-related. CONCLUSIONS: Renal grafts showed a stronger immunogenicity than other sources of allosensitization. Our data also suggest that CREG matching may not be useful for renal allocation.

Antibodies↗
PubMed1999

Different roles for LFA-1 and VLA-4 integrins in T-B-cell interactions in vivo.

Adhesion molecules are critical in the cellular interactions involved in specific immune responses. They are used for homing, cell migration, cell-cell contact and, in some cases, for the delivery of costimulatory signals. Since the host-versus-graft (HVG) reaction represents a particular form of T-B-cell interaction, we have explored whether the inhibition of lymphocyte function-associated antigen-1/intracellular adhesion molecule-1 (LFA-1/ICAM-1) interactions and the signalling through very late activation antigen-4 (VLA-4) have any effect on the development of a lupus-like disease in BALB/c mice injected at birth with (BALB/cxC57BL/6)F1 spleen cells. In close association with the development of tolerance to donor allografts, these mice show a polyclonal activation of F1 donor B cells by alloreactive host CD4+ T cells, manifested by the production of autoantibodies (autoAbs) and the development of a mild glomerulonephritis. The dose of the monoclonal antibody (mAb) employed has been adjusted to block completely the molecule on the surface of peripheral lymphocytes without interfering with the induction of neonatal tolerance. Injection of saturating doses (100 microg/2 days) of either anti-LFA-1alpha or anti-ICAM-1 mAbs, but not anti-VLA-4alpha or anti-LFA-1beta mAbs, blocks the production of anti-ssDNA autoAbs and the thrombocytopenia characteristic of this HVG disease (HVGD). However, anti-VLA-4alpha treatment is only able to delay the production of autoAbs and the anti-LFA-1beta treatment, not to modify the evolution of the HVGD. These results point to the relevance of LFA-1/ICAM-1 interactions, but not of the VLA-4-mediated signal, in the polyclonal B-cell activation occurring during the allogeneic interactions between host T helper type 2 cells and donor B cells in HVGD.

Animals↗