Institute Investigacion Hospital Universitario 12 Of Octubre

Madrid, Spain

Institute Investigacion Hospital Universitario 12 Of Octubre

Madrid, Spain

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Ruiz-Garcia R.,Institute Investigacion Hospital Universitario 12 Of Octubre | Serrano M.,Institute Investigacion Hospital Universitario 12 Of Octubre | Angel Martinez-Flores J.,Institute Investigacion Hospital Universitario 12 Of Octubre | Mora S.,Institute Investigacion Hospital Universitario 12 Of Octubre | And 7 more authors.
Journal of Immunology Research | Year: 2014

Seronegative antiphospholipid syndrome (SNAPS) is an autoimmune disease present in patients with clinical manifestations highly suggestive of Antiphospholipid Syndrome (APS) but with persistently negative consensus antiphospholipid antibodies (a-PL). IgA anti-β2 Glycoprotein I (aB2-GPI) antibodies are associated with APS. However, they are not currently considered to be laboratory criteria due to the heterogeneity of published works and the use of poor standardized diagnostic systems. We have aimed to assess aPL antibodies in a group of patients with clinical manifestations of APS (C-APS) to evaluate the importance of the presence of IgA aB2GPI antibodies in APS and its relation with other aPL antibodies. Only 14% of patients with C-APS were positive for any consensus antibody, whereas the presence of isolated IgA aB2GPI antibodies was found in 22% of C-APS patients. In patients with arterial thrombosis IgA aB2GPI, antibodies were the only aPL antibodies present. Serologic profile in primary APS (PAPS) is different from systemic autoimmune disorders associated APS (SAD-APS). IgA aB2GPI antibodies are more prevalent in PAPS and IgG aB2GPI antibodies are predominant in SAD-APS. The analysis of IgA aB2GPI antibodies in patients with clinical manifestations of PAPS might avoid underdiagnosed patients and provide a better diagnosis in patients with SAD-APS. Laboratory consensus criteria might consider including analysis of IgA aB2GPI for APS diagnosis. © 2014 Raquel Ruiz-García et al.


Martinez-Flores J.A.,Institute Investigacion Hospital Universitario 12 Of Octubre | Serrano M.,Institute Investigacion Hospital Universitario 12 Of Octubre | Morales P.,Institute Investigacion Hospital Universitario 12 Of Octubre | Paz-Artal E.,Institute Investigacion Hospital Universitario 12 Of Octubre | And 4 more authors.
Journal of Immunological Methods | Year: 2014

The introduction of new immunosuppressive drugs in the last two decades has been associated with a significant decline in the prevalence of acute rejection and a huge improvement of graft survival. Monitoring blood levels of immunosuppressive drugs is the most common way to control drug doses in renal transplant patients. This approach is useful and widely used but doesn't give accurate information about the immune status of the patient. For this goal, there are many "in house" protocols which give more information, but cannot be standardized, limiting their applicability to compare results between different laboratories. In this study we compare three classical functional methods to evaluate the immune response: Mixed lymphocyte reaction (MLR), phytohemagglutinin stimulated peripheral blood lymphocytes (PBLs), and anti-CD3 monoclonal antibodies (mAbs) against PBL with the only FDA-labeled assay to measure the patient immune status: Cylex ImmuKnow® that measures the intracelullar ATP in CD4. + lymphocytes. We used n. = 111 stable renal transplant patients, all the patients with more than one year functioning grafts. We referred the results to a control population of healthy blood donors (n. = 125).Results: Measurement of intracellular ATP in CD4. + lymphocytes is able to differentiate immunosuppressed populations in renal transplant patients from health controls (242.30. ±. 21.62 vs. 386.43. ±. 25.12, p 0.0001). By contrary, there were no differences between controls and renal recipients when functional response was measured by MLR, PHA and anti-CD3 mAbs (2.48. ±. 0.45 vs. 2.37. ±. 0.41; 2.84. ±. 0.76 vs. 2.37. ±. 0.32; 2.32. ±. 0.34 vs. 1.89. ±. 0.38 respectively). In summary, our results show that the measurement of ATP in CD4. + lymphocytes gives more accurate information in comparison to the classical methods. © 2013 Elsevier B.V.


Aguera-Ortiz L.,Institute Investigacion Hospital Universitario 12 Of Octubre | Cuervo J.,LA SER Group | Medina E.,Astrazeneca | Diaz-Cuervo H.,LA SER Group | Maurino J.,Astrazeneca
Actas Espanolas de Psiquiatria | Year: 2013

Objective: To adapt the CUDOS scale (Clinically Useful Depression Outcome Scale) into Spanish and to test its psychometrical properties in a sample of patients with major depressive disorder (MDD). Methods: A two-step cross-sectional, multicenter validation study was conducted (linguistic adaptation into Spanish and psychometric validation). The study evaluated patients attended in Primary Care with a MDD diagnosis within the last 3 months (DSM-IV TR criteria). The following scales were administered: CUDOS, PRIME-MD (Primary Care Evaluation of Mental Disorders), HAMD-17 (Hamilton Depression Rating Scale), SOFAS (Social and Occupational Functioning Assessment Scale), SF-36 (Physical-PCS- and Mental-MCS-Component Summaries), and the CGI-S &PGI-S (Clinical Global Impression for Severity of Illness scales for clinicians and patients, respectively). Feasibility, reliability, and validity of the Spanish version were assessed. Results: In the validation study, 305 MDD patients (69.5% female) with a mean age (standard deviation-SD-) of 51.75(15.53) were included. Mean completion time was 4.47(2.4) minutes. Floor or ceiling effects were found in less than 1%of the case scores. Internal consistency was adequate (Cronbach's α= 0.88). Pearson correlation coefficients with CUDOS were:-0.42 (SOFAS), 0.45 (HAMD-17), -0.22 (PCS), -0.65 (MCS);all p<0.001. The CUDOS properly discriminated among clinical severity levels (p<0.03). Conclusions: The adapted Spanish version of the CUDOS shows adequate psychometric properties as an evaluation instrument of major depression from the patient's perspective.


PubMed | University of San Pablo - CEU and Institute Investigacion Hospital Universitario 12 Of Octubre
Type: Comparative Study | Journal: Journal of immunological methods | Year: 2014

The introduction of new immunosuppressive drugs in the last two decades has been associated with a significant decline in the prevalence of acute rejection and a huge improvement of graft survival. Monitoring blood levels of immunosuppressive drugs is the most common way to control drug doses in renal transplant patients. This approach is useful and widely used but doesnt give accurate information about the immune status of the patient. For this goal, there are many in house protocols which give more information, but cannot be standardized, limiting their applicability to compare results between different laboratories. In this study we compare three classical functional methods to evaluate the immune response: Mixed lymphocyte reaction (MLR), phytohemagglutinin stimulated peripheral blood lymphocytes (PBLs), and anti-CD3 monoclonal antibodies (mAbs) against PBL with the only FDA-labeled assay to measure the patient immune status: Cylex ImmuKnow that measures the intracelullar ATP in CD4+ lymphocytes. We used n=111 stable renal transplant patients, all the patients with more than one year functioning grafts. We referred the results to a control population of healthy blood donors (n=125).Measurement of intracellular ATP in CD4+ lymphocytes is able to differentiate immunosuppressed populations in renal transplant patients from health controls (242.3021.62 vs. 386.4325.12, p 0.0001). By contrary, there were no differences between controls and renal recipients when functional response was measured by MLR, PHA and anti-CD3 mAbs (2.480.45 vs. 2.370.41; 2.840.76 vs. 2.370.32; 2.320.34 vs. 1.890.38 respectively). In summary, our results show that the measurement of ATP in CD4+ lymphocytes gives more accurate information in comparison to the classical methods.


PubMed | Centro Nacional Investigaciones Cardiovasculares Carlos III CNIC, Ikerbasque, Institute Investigacion Hospital Universitario 12 Of Octubre, IIS Fundacion Jimenez Diaz and Instituto Investigacion Sanitaria Princesa
Type: Journal Article | Journal: Cell metabolism | Year: 2015

The endolysosomal system is critical for the maintenance of cellular homeostasis. However, how endolysosomal compartment is regulated by mitochondrial function is largely unknown. We have generated a mouse model with defective mitochondrial function in CD4(+) T lymphocytes by genetic deletion of the mitochondrial transcription factor A (Tfam). Mitochondrial respiration deficiency impairs lysosome function, promotes p62 and sphingomyelin accumulation, and disrupts endolysosomal trafficking pathways and autophagy, thus linking a primary mitochondrial dysfunction to a lysosomal storage disorder. The impaired lysosome function in Tfam-deficient cells subverts T cell differentiation toward proinflammatory subsets and exacerbates the in vivo inflammatory response. Restoration of NAD(+) levels improves lysosome function and corrects the inflammatory defects in Tfam-deficient T cells. Our results uncover a mechanism by which mitochondria regulate lysosome function to preserve T cell differentiation and effector functions, and identify strategies for intervention in mitochondrial-related diseases.


PubMed | University of San Pablo - CEU and Institute Investigacion Hospital Universitario 12 Of Octubre
Type: | Journal: Journal of immunological methods | Year: 2015

Patients with antiphospholipid syndrome (APS) have a hypercoagulable condition associated with the presence of antiphospholipid autoantibodies (aPL). Consensus antibodies for diagnosis are lupus anticoagulant, anti-beta2 glycoprotein I (B2GPI) and anticardiolipin (IgG or IgM). Circulating immunocomplexes (CIC) of B2GPI associated with IgM or IgG were reported. Isolated IgA aB2GPI antibodies have achieved high diagnostic value although specific CIC of B2GPI bounded to IgA (B2A-CIC) has still not been described. CIC detection assays are mainly based on interaction with complement and are not appropriate to detect B2A-CIC because IgA does not fix complement using the classical pathway.Sera from healthy blood donors (N= 247) and from patients with thrombosis background and isolate positive for IgA aB2GPI (N = 68) were studied in a case-control study. Two methods were applied, these being a capture ELISA to quantify specific B2A-CIC and quantification of total IgA anti-B2GPI after dissociating CIC.B2A-CIC values in APS-patients were 19.27 2.6 AU vs 6.1 0.4 AU in blood donors (p < 0.001). There were 36.4% B2A-CIC positive patients (cutoff 21 AU) versus 5.5% in blood donors (p < 0.001). Dissociated IgA aB2GPI levels (total IgA aB2GPI) were 146.8 10.8 IU/mL in patients vs. 22.4 IU/mL in controls (p < 0.001). B2A-CIC was independent of B2GPI and autoantibodies IgA aB2GPI serum levels.B2A-CIC can be identified and quantified in an easy and reproducible manner using two complement-independent methods. The use of these tests in prospective studies will allow better understanding of the prognosis and outcome of patients.


Jurado-Barba R.,Institute Investigacion Hospital Universitario 12 Of Octubre | Jurado-Barba R.,Research Center Biomedica En Red Of Salud Mental | Jurado-Barba R.,Hospital Universitario 12 Of Octubre | Morales-Munoz I.,Institute Investigacion Hospital Universitario 12 Of Octubre | And 12 more authors.
Psychiatry Research | Year: 2011

Disruption of prepulse inhibition of the startle response (PPI) has been widely identified in patients with schizophrenia, as well as impairment in many domains of cognitive functioning. However, there is some controversy regarding the relationship between PPI and the different neuropsychological tasks assessing inhibition. This controversy may be due to the influence of other variables, such as substance abuse. We aimed to determine whether differences in inhibition in schizophrenia subjects were related to their pattern of substance use and whether there was a correlation between the changes in each process. PPI and neuropsychological functioning were studied in three groups of subjects with schizophrenia (N= 73): tobacco dependents (ToD; n= 22), multiple substance abusers (MSUD; n= 31) and non-substance abusers (non-SUD; n= 20). All subjects were assessed using PPI and neuropsychological tests (Stroop and Wisconsin Card Sorting Test [WCST]). ToD showed better pre-attentive inhibitory function compared to the other two groups, and MSUD showed lower resistance to interference. Furthermore, significant correlations were found between PPI, Stroop, and WCST. Our data suggest that there is a relationship between the different tasks assessing inhibition in schizophrenia, being affected by substance abuse history. We also found differences in inhibition capacity depending on substance abuse in patients with schizophrenia. © 2011 Elsevier Ltd.


del-Castillo-Rueda A.,Institute Investigacion Sanitaria del Hospital General Universitario Gregorio Maranon | del-Castillo-Rueda A.,Complutense University of Madrid | Moreno-Carralero M.-I.,Institute Investigacion Hospital Universitario 12 Of Octubre | Cuadrado-Grande N.,Institute Investigacion Hospital Universitario 12 Of Octubre | And 6 more authors.
Gene | Year: 2012

Hereditary hemochromatosis causes iron overload and is associated with a variety of genetic and phenotypic conditions. Early diagnosis is important so that effective treatment can be administered and the risk of tissue damage avoided. Most patients are homozygous for the c.845G>A (p.C282Y) mutation in the HFE gene; however, rare forms of genetic iron overload must be diagnosed using a specific genetic analysis. We studied the genotype of 5 patients who had hyperferritinemia and an iron overload phenotype, but not classic mutations in the HFE gene. Two patients were undergoing phlebotomy and had no iron overload, 1 with metabolic syndrome and no phlebotomy had mild iron overload, and 2 patients had severe iron overload despite phlebotomy. The patients' first-degree relatives also underwent the analysis. We found 5 not previously published mutations: c.-408_-406delCAA in HFE, c.1118G>A (p.G373D), c.1473G>A (p.E491E) and c.2085G>C (p.S695S) in TFR2; and c.-428_-427GG>TT in SLC40A1. Moreover, we found 3 previously published mutations: c.221C>T (p.R71X) in HFE; c.1127C>A (p.A376D) in TFR2; and c.539T>C (p.I180T) in SLC40A1. Four patients were double heterozygous or compound heterozygous for the mutations mentioned above, and the patient with metabolic syndrome was heterozygous for a mutation in the TFR2 gene. Our findings show that hereditary hemochromatosis is clinically and genetically heterogeneous and that acquired factors may modify or determine the phenotype. © 2012.


PubMed | Institute Investigacion Hospital Universitario 12 Of Octubre
Type: Journal Article | Journal: Kidney international | Year: 2012

Cardiovascular complications are the most important cause of death in patients on dialysis with end-stage renal disease. Antibodies reacting with -glycoprotein I seem to play a pathogenic role in antiphospholipid syndrome and stroke and are involved in the origin of atherosclerosis. Here we evaluated the presence of anticardiolipin and anti--glycoprotein I antibodies together with other vascular risk factors and their relationship with mortality and cardiovascular morbidity in a cohort of 124 hemodialysis patients prospectively followed for 2 years. Of these, 41 patients were significantly positive for IgA anti--glycoprotein I, and the remaining had normal values. At 24 months, overall and cardiovascular mortality and thrombotic events were all significantly higher in patients with high anti--glycoprotein I antibodies. Multivariate analysis using Cox regression modeling found that age, hypoalbuminemia, use of dialysis catheters, and IgA -glycoprotein I antibodies were independent risk factors for death. Thus, IgA antibodies to -glycoprotein I are detrimental to the clinical outcome of hemodialysis patients.


PubMed | Institute Investigacion Hospital Universitario 12 Of Octubre
Type: Journal Article | Journal: Psychiatry research | Year: 2011

Disruption of prepulse inhibition of the startle response (PPI) has been widely identified in patients with schizophrenia, as well as impairment in many domains of cognitive functioning. However, there is some controversy regarding the relationship between PPI and the different neuropsychological tasks assessing inhibition. This controversy may be due to the influence of other variables, such as substance abuse. We aimed to determine whether differences in inhibition in schizophrenia subjects were related to their pattern of substance use and whether there was a correlation between the changes in each process. PPI and neuropsychological functioning were studied in three groups of subjects with schizophrenia (N=73): tobacco dependents (ToD; n=22), multiple substance abusers (MSUD; n=31) and non-substance abusers (non-SUD; n=20). All subjects were assessed using PPI and neuropsychological tests (Stroop and Wisconsin Card Sorting Test [WCST]). ToD showed better pre-attentive inhibitory function compared to the other two groups, and MSUD showed lower resistance to interference. Furthermore, significant correlations were found between PPI, Stroop, and WCST. Our data suggest that there is a relationship between the different tasks assessing inhibition in schizophrenia, being affected by substance abuse history. We also found differences in inhibition capacity depending on substance abuse in patients with schizophrenia.

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