[Renal involvement in antineutrophil cytoplasmic antibodies (ANCA) associated vasculitides. Recommendations of the Chilean Societies of Nephrology and Rheumatology]. / Compromiso renal en vasculitis asociadas a anticuerpos anticitoplasma de neutrófilos. Recomendaciones de consenso de las Sociedades Chilenas de Nefrología y Reumatología.

Renal involvement is a frequent complication in antineutrophil cytoplasmic antibodies (ANCA)associated vasculitides, adding morbidity and mortality, such as chronic kidney disease and the need for renal replacement therapy. With the aim of reaching a consensus on relevant issues regarding the diagnosis, treatment and follow-up of patients with these diseases, the Chilean Societies of Nephrology and Rheumatology formed a working group that, based on a critical review of the available literature and their experience, raised and answered consensually a set of questions relevant to the subject. This document includes aspects related to the clinical diagnosis, the histological characteristics, the therapeutic alternatives to induce and maintain the remission of the disease, relapse surveillance strategies and complementary therapies.

The essential role of chemokines in the selective regulation of lymphocyte homing.

Knowledge of lymphocyte migration has become a major issue in our understanding of acquired immunity. The selective migration of naïve, effector, memory and regulatory T-cells is a multiple step process regulated by a specific arrangement of cytokines, chemokines and adhesion receptors that guide these cells to specific locations. Recent research has outlined two major pathways of lymphocyte trafficking under homeostatic and inflammatory conditions, one concerning tropism to cutaneous tissue and a second one related to mucosal-associated sites. In this article we will outline our present understanding of the role of cytokines and chemokines as regulators of lymphocyte migration through tissues.

Cyclosporin A-treated dendritic cells may affect the outcome of organ transplantation by decreasing CD4+CD25+ regulatory T cell proliferation.

One of the mechanisms for generation of tolerance involves immature dendritic cells (DCs) and a subpopulation of regulatory CD4+ CD25+ T lymphocytes (T REG). The purpose of this work was to analyze how Cyclosporine A (CsA), a widely used immunosuppressive drug, may affect T REG proliferation. Purified and activated murine DCs obtained from bone marrow precursors differentiated with rGMCSF were co-cultured with purified CFSE-labeled T REG from OTII mice, and their phenotype and proliferation analyzed by flow cytometry. Our data indicate that DCs differentiated in the presence of CsA show an altered phenotype, with a lower expression of MHC-II and a lower activating capacity. Additionally, these CsA-treated DCs show decreased production of IL-2 and IL-12 and increased IL-10 secretion when stimulated with LPS, indicating an effect on the polarization of the immune response. Interestingly, CsA-treated DCs show an anti-tolerogenic effect since they reduce the proliferation of T REG cells from 72 to 47%. Further inhibition to a 24% of T REG proliferation was obtained as a direct effect of CsA on T REG. In conclusion, the anti-tolerogenic effect of CsA should be considered in the planning of immunosuppression in the context of clinical transplantation.

Compromiso renal en vasculitis asociadas a anticuerpos anticitoplasma de neutrófilos. Recomendaciones de consenso de las Sociedades Chilenas de Nefrología y Reumatología / Renal involvement in antineutrophil cytoplasmic antibodies (ANCA) associated vasculitides. Recommendations of the Chilean Societies of Nephrology and Rheumatology

Renal involvement is a frequent complication in antineutrophil cytoplasmic antibodies (ANCA)associated vasculitides, adding morbidity and mortality, such as chronic kidney disease and the need for renal replacement therapy. With the aim of reaching a consensus on relevant issues regarding the diagnosis, treatment and follow-up of patients with these diseases, the Chilean Societies of Nephrology and Rheumatology formed a working group that, based on a critical review of the available literature and their experience, raised and answered consensually a set of questions relevant to the subject. This document includes aspects related to the clinical diagnosis, the histological characteristics, the therapeutic alternatives to induce and maintain the remission of the disease, relapse surveillance strategies and complementary therapies.

Cyclosporin A-treated Dendritic Cells may affect the outcome of organ transplantation by decreasing CD4+CD25+ regulatory T cell proliferation

One of the mechanisms for generation of tolerance involves immature dendritic cells (DCs) and a subpopulation of regulatory CD4+ CD25+ T lymphocytes (T REG). The purpose of this work was to analyze how Cyclosporine A (CsA), a widely used immunosuppressive drug, may affect T REG proliferation. Purified and activated murine DCs obtained from bone marrow precursors differentiated with rGMCSF were co-cultured with purified CFSE-labeled T REG from OTII mice, and their phenotype and proliferation analyzed by flow cytometry. Our data indicate that DCs differentiated in the presence of CsA show an altered phenotype, with a lower expression of MHC-II and a lower activating capacity. Additionally, these CsA-treated DCs show decreased production of IL-2 and IL-12 and increased IL-10 secretion when stimulated with LPS, indicating an effect on the polarization of the immune response. Interestingly, CsA-treated DCs show an anti-tolerogenic effect since they reduce the proliferation of T REG cells from 72 to 47 percent. Further inhibition to a 24 percent of T REG proliferation was obtained as a direct effect of CsA on T REG. In conclusion, the anti-tolerogenic effect of CsA should be considered in the planning of immunosuppression in the context of clinical transplantation.

[Clinical applications of antigen-specific detection of T lymphocytes]. / La detección antígeno-específica de linfocitos T y sus aplicaciones clínicas.

The important role that T lymphocytes play during the immune response against pathogens and tumor cells has encouraged the development of technologies aimed to detect these immune cells in an antigen-specific fashion. Recently, a methodology consisting of the production of soluble ligands that bind the T lymphocyte receptor was developed. Such ligands consist of molecules from the Major Histocompatibility Complex loaded with either pathogen or tumor derived peptides. These molecular complexes are tetramerized to enhance the binding efficiency to the T cell receptor (TCR), which improves the detection sensitivity of antigen specific T lymphocytes. This new technology is currently used successfully during the follow up patients that were vaccinated against certain tumor antigens, to evaluate the expansion of tumor specific T lymphocytes. This methodology is also promising for the detection and specific deletion of autoreactive T lymphocytes as a treatment for autoimmune disorders. In this article we review the molecular components involved in antigen recognition by T lymphocytes, and the potential benefits for Biomedicine that could result from the detection of these cells by soluble specific ligands.

[Epidemiology of hypertension in chronic hemodialysis]. / Epidemiología de la hipertensión en hemodiálisis crónica.

BACKGROUND: Hypertension is a common and important cardiovascular risk factor in patients on chronic hemodialysis. AIM: To report the prevalence and characteristics of hypertension among patients on chronic hemodialysis. PATIENTS AND METHODS: Cross sectional study of 313 patients (192 male, aged 57 +/- 18 years) dialyzed in 7 representative centers in Santiago, Chile. RESULTS: Patients were on hemodialysis for a mean of 68 +/- 53 months and 67 (21%) were diabetic. 230 (74%) were hypertensive and 223 of these (97%) had predialysis hypertension. A multivariate analysis showed that hypertension was associated with increased weight gain between dialysis, failure to achieve the postdialysis dry weight, increasing age and the presence of diabetes. Among hypertensive patients, 61% were receiving antihypertensive medications, compared with 27% of patients with normal blood pressure. CONCLUSIONS: High blood pressure is highly prevalent among patients on chronic hemodialysis and is associated to hypervolemia, age and the presence of diabetes.

A simple method to calculate cyclosporine dosage to obtain a target C2 drug level.

C(2) Cyclosporine (CsA) level, as a surrogate of area under the time-concentration curve (AUC) 0-4 hours, is a good predictor of drug absorption and clinical outcome after kidney transplantation. It has been difficult to define the optimal C(2) level in the individual case and given the broad range of C(2) due to interindividual absorption variability it has been troublesome to determine the drug dose needed to obtain an expected C(2)-CsA concentration. In this study data of 16 stable renal and renal/pancreas recipients treated with prednisone, azathioprine, and CsA (Neoral) managed by C(0) level was examined. CsA concentrations at time 0 (basal), 2, 6, and 12 hours post CsA (Neoral) intake were determined the day of the study. A significant linear regression level was established between C(2) (but not C(0), C(6) and C(12)) and the dosage expressed as mg/kg/d (P = 0.0113, correlation coefficient r = 0.573018). Subsequently, another 27 renal transplant recipients were studied retrospectively and divided into three groups according to posttransplant period: 1 to 6, 7 to 12, and beyond 12 months after transplant. Equations derived from the relationship between C(2) and dose (mg/kg/d) were similar between the three groups and when compared with the first study. A formula obtained from the 27 patients in the whole posttransplant period (mg/kg/d = C(2) x 0.0010208 + 1.86125) was applied to patients of the first study obtaining a regression coefficient between actual and calculated CsA dose of 0.6145 (P = 0.01). A more accurate equation (P = 0.0001, r = 0.5925) was obtained by analyzing 145 C(2) determinations covering a period from 1 month to 8 years following transplant which gave a linear regression line defined by the equation C(2) x 0.001473 + 1.6673. This equation would permit the calculation mg/kg/d of CsA (Neoral) dose to obtain an expected C(2) level. The derived equation shown in this paper has a predictive value of 50% to 60% only, but can help to find adequate dosage in the presence of an inappropriate C(2) level.

La detección antígeno-específica de linfocitos T y sus aplicaciones clínicas / Clinical applications of antigen-specific detection of T lymphocytes

The important role that T lymphocytes play during the immune response against pathogens and tumor cells has encouraged the development of technologies aimed to detect these immune cells in an antigen-specific fashion. Recently, a methodology consisting of the production of soluble ligands that bind the T lymphocyte receptor was developed. Such ligands consist of molecules from the Major Histocompatibility Complex loaded with either pathogen or tumor derived peptides. These molecular complexes are tetramerized to enhance the binding efficiency to the T cell receptor (TCR), which improves the detection sensitivity of antigen specific T lymphocytes. This new technology is currently used successfully during the follow up patients that were vaccinated against certain tumor antigens, to evaluate the expansion of tumor specific T lymphocytes. This methodology is also promising for the detection and specific deletion of autoreactive T lymphocytes as a treatment for autoimmune disorders. In this article we review the molecular components involved in antigen recognition by T lymphocytes, and the potential benefits for Biomedicine that could result from the detection of these cells by soluble specific ligands (Rev MÚd Chile 2004; 132: 371-80).