Oviedo, Spain
Oviedo, Spain

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Bosca I.,Hospital Universitario La Paz | Villar L.M.,Immunology Service | Coret F.,Hospital Clinic Of Valencia | Magraner M.J.,Hospital Universitario La Paz | And 3 more authors.
Multiple Sclerosis | Year: 2010

The objective of this study was to investigate whether the presence of lipid-specific oligoclonal IgM bands (LS-OCMB) in cerebrospinal fluid (CSF) influences the response to treatment with beta-interferon in relapsing-remitting multiple sclerosis (RRMS) patients. We performed a collaborative prospective study including RRMS patients with brain MRI and LS-OCMB studies performed before starting interferon treatment. The primary endpoint was the risk of having a relapse after treatment initiation. Secondary endpoints included relapse rate, relapse-rate reduction, proportion of relapse-free patients and proportion of patients with sustained disability increase during follow-up. One-hundred and two patients were included. After a mean follow-up of 37.4 months, the risk of suffering a relapse was two-fold higher in patients with LS-OCMB (hazard ratio 2.0, 95% confidence interval 1.1-3.8). LS-OCMB+ patients showed lower reduction in relapse rate (51.8% versus 80.8%; p < 0.0001), higher relapse rate in the first year (0.8 versus 0.2; p = 0.001), lower proportion of relapse-free patients (25% versus 61.3%; p = 0.003), and higher proportion of patients with sustained 1.0 increase in the Expanded Disability Status Score (45% versus 12.9%; p = 0.0003). In conclusion, LS-OCMB can have an influence on the response to interferon treatment in RRMS patients. They could be used as a biological marker to predict high inflammatory activity after treatment.© 2010 The Author(s).Indications:39 patients with relapsing remitting multiple sclerosis.TypeofStudy:An open, multicenter study investigating whether the presence or absence of lipid-specific oligoclonal immunoglobulin M (IgM) bands (LS-OCMB) had an influence on the time to a new relapse, the proportion of relapse-free patients, and the disability progression during interferon (IFN) treatment (including Extavia), in patients with relapsing remitting multiple sclerosis (RRMS).Patients:102 patients, 28 males and 74 females, mean age 33.0 years; 39 were on Extavia, and 63 interferon beta 1a (44 Rebif and 19 Avonex); 40 LS-OCMB+ (13 males and 27 females, mean age 31.5 years), and 62 LS-OCMB- (15 males and 47 females, mean age 34.1 years). Follow-up: mean of 34.8 months.DosageDuration:Dosage not stated. Duration: mean of 34.8 months.Results:Results were given for the whole group of patients receiving IFN without separate data for Extavia. OCGB were present in 96.1% of the patients, OCMB in 46.1%, and LS-OCMB in 39.2%. 1 year after treatment initiation, only 5 patients had NAbs (2 LS-OCMB+ and 3 LS-OCMB-). No differences were noted in the incidence of NAbs between LS-OCMB+ and - patients. 53 patients suffered at least 1 relapse during treatment. The probability of having a relapse after treatment initiation was significantly higher for the LS-OCMB+ group, with a shorter time to relapse compared to LS-OCMB- patients. Among the variables for relapse, only the presence of LS-OCMB showed a higher risk of a second relapse. A significant reduction was noted in the relapse rate during the first year of IFN in both groups, although the reduction was lower in patients with LS-OCMB. These patients showed a higher relapse rate in the first year under treatment and the proportion of relapse-free patients was lower in the LS-OCMB+ group. After a mean follow-up of 34.8 months, higher EDSS score was noted in LS-OCMB+ patients. Patients lacking LS-OCMB remained stable during the study. The proportion of patients that increased in at least one point EDSS score during treatment was also higher for patients with LS-OCMB.AdverseEffects:No adverse events were mentioned.AuthorsConclusions:We think that our results have important clinical implications. LS-OCMB determination can help us to detect patients in which IFN treatment can be more effective (LS-OCMB-) and those at risk of an incomplete response (LS-OCMB+). Further research should be performed to investigate whether these patients would better benefit from other disease-modifying drugs since onset.FreeText:Primary endpoint: the time to first relapse after treatment initiation. Secondary endpoints: follow-up relapse rate, relapse-rate reduction, the proportion of relapse-free patients, mean Expanded Disability Status Scale (EDSS), and the proportion of patients with disability increase defined as ≥1.0 sustained increase in the EDSS (confirmed 3 months later) during follow-up. Tests: serum and cerebrospinal fluid levels of oligoclonal IgG band (OCGB), oligoclonal IgM bands (OCMB), and LS-OCMB; levels of neutralizing antibodies (NAbs); and magnetic resonance imaging. Concomitant drugs: steroids, given as high dose.

Queiro R.,Hospital Universitario Central Of Asturias Huca | Tejon P.,Hospital Universitario Central Of Asturias Huca | Coto P.,Hospital Universitario Central Of Asturias Huca | Alonso S.,Hospital Universitario Central Of Asturias Huca | And 6 more authors.
Clinical and Developmental Immunology | Year: 2013

It has been shown that males with spondyloarthritis tend to suffer from more severe spinal disease while females are more likely to have peripheral joint involvement. Nevertheless, gender-related differences have not been thoroughly explored in psoriatic arthritis (PsA). In PsA, males accumulate more peripheral and axial joint damage compared to women. However, it is not clear whether these findings are secondary to differences in occupational physical activity, hormonal changes, or other factors. The present study analyzed the differences in clinical expression of PsA between men and women. We have also evaluated the possible existence of gender-linked differences in the distribution of genes and polymorphisms within the major histocompatibility complex and whether patients' age at the onset of psoriasis established any differences in these aspects. Women suffered more polyarthritis, greater functional impairment, and a larger number of swollen joints during followup. We appreciated a differential expression of certain MHC genes according to gender and age at onset of psoriasis. Our results point to the need to include patient's age at the onset of psoriasis and gender as key stratification elements in future studies of genetic associations in PsA. © 2013 Rubén Queiro et al.

Castiella A.,Mendaro Hospital | Zapata E.,Mendaro Hospital | De Juan M.D.,Immunology Service | Otazua P.,Mondragon Hospital | And 3 more authors.
Journal of Gastroenterology and Hepatology (Australia) | Year: 2010

Background: The significance of H63D homozygosity remains uncertain, although it is associated with a tendency for patients to develop iron overload. Aims: To study the prevalence of homozygotic H63D mutation in patients with phenotypic hemochromatosis (PH) and to compare the results with those of the general population and with patients with porphyria cutanea tarda (PCT) in the Basque Country, Spain. A secondary aim was to evaluate the differences in phenotypic expression and liver injury according to different genotypes in the PH cohort. Methods: Mutations of the HFE gene were obtained by polymerase chain reaction (PCR). Forty consecutive patients diagnosed with PH, 116 controls and 54 patients with PCT were included in the study. We performed liver biopsies, measured liver iron concentration (LIC), by atomic spectrophotometry, serum ferritin and transferrin saturation, and compared the histology according to the genotype. Results: The H63D homozygote mutation was identified in 7.76% of the control group, in 7.50% of the PH group, and in 11.11% of patients with PCT (P > 0.05). The C282Y/C282Y mutation was present in 50% of patients with PH, and LIC was identified in 15/20. The LIC in C282Y/C282Y patients was higher than in H63D/H63D patients (P = 0.26), while H63D homozygosis caused greater iron overload in PH patients than other genotypes. All the C282Y/C282Y genotype patients had elevated serum ferritin and transferrin saturation. The H63D homozygotes had high ferritin, but two out of three had normal transferrin saturation. Six of the eight patients with high-grade fibrosis and genetic study results were found to be C282Y/C282Y. Conclusions: The prevalence of H63D mutation in patients with PH in our region does not differ from that of the general Basque population. © 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

PubMed | Radiology, Epidemiology Unit, Immunology Service, Gastroenterology and Mondragon Hospital
Type: Journal Article | Journal: Annals of hepatology | Year: 2015

There are limited data on clinical and phenotypic characteristics of outpatients referred for hyperferritinemia (HF). To determine the causes of HF in outpatients referred to a secondary hospital.A prospective study of 132 consecutive patients with HF (> 200 g/L, women; > 300 g/L, men) was conducted from January-December 2010.Mean age, 54.42 years (SD: 13.47, range: 23-83); body mass index (BMI), 28.80 (SD: 3.96, 17-39); ferritin (SF), 579.54 ng/mL (SD: 296.575, 206-1668); transferrin saturation (TSI), 43.87% (SD: 14.09, 12-95); iron (Fe), 134 g/dL (SD: 49.68, 55-322); overweight: 48.31%, and obese: 40.44% (89%), and most patients were men (108/132). Regarding HFE mutations, H63D/H63D genotype and H63D allele frequencies were 17.5% (vs. 7.76% in controls); and 36% (31% in controls) respectively. While 63.6% consumed no alcohol, 18.1% consumed 60 g/day, the mean being 20.83 (SD: 33.95, 0-140). Overall, 6/132 (4.5%) patients were positive for B or C hepatitis. Mean LIC by MRI was 36.04 (SD: 32.78, 5-210), 53 patients having normal concentrations (< 36 mol/g), 22 (33%) iron overload (37-80), and 4 (5%) high iron overload (> 80). Metabolic syndrome (MS) was detected in 44/80 men (55%) and 10/17 women (59%). In this group, the genotype frequency of the H63D/H63D mutation was significantly higher than in controls-21.56% vs. 7.76%- (p = 0.011); the H63D allelic frequency was 42.15% in MS group and 31% in controls (p = 0.027).The H63D/H63D genotype and H63D allele predispose individuals to HF and MS. MRI revealed iron overload in 33% of patients.

Ribizzi G.,Ospedale S. Martino | Fiordoro S.,Immunology Service | Barocci S.,Immunology Service | Ferrari E.,Immunology Service | Megna M.,University of Bari
Neurological Sciences | Year: 2010

Alzheimer's disease (AD) is a degenerative dementia characterized by typical, destructive alterations of neurons (neurofibrillary tangles and amyloid plaques), and glial proliferation. Cytokine-driven inflammatory environment can contribute to the pathogenesis and/or progression of the disease. The aim of the study was to evaluate andcompare genotypic and allelic polymorphisms of 13 cytokine genes in 19 Caucasoid AD patients with medium-high level of dementia (assessed by an MMSE<24) and 20 normal controls affected by non inflammatory neuropsychiatric disease. Polymorphisms in the genes of IL-lA, ILlB, IL-2, IL-4, IL-6, IL-10, IL-12, IFN-G, TGF-β, TNF-α, and of the cytokine receptors IL-lR, IL-IRA, IL-4RA were investigated. APO-E and ACE gene polymorphisms were carried out in the patient's group only to evaluate a possible association with known genetic risk factors for AD. A highly significant presence of some alleles belonging to anti-inflammatory cytokine genes was found; particularly the C allele for the -590 promoter and T allele for the -1098 promoter of IL-4 appeared in a significantly higher percentage as compared with controls (P<0.0006 and P<0.0005, respectively), while a lesser significance was observed for the allele C of the -819 promoter of IL-10 (P<0.03). Finally, in the group of demented patients for the APO-E gene we found a statistically significant presence of the E4 allele, whereas no difference was found for the polymorphisms of the ACE gene. Our observations corroborate the possible presence of a pro-inflammatory environment in AD patients, partly sustained by the low expression of anti-inflammatory cytokine genes when defined alleles are present. Large cohort studies are necessary in order to assess the real association of some cytokine alleles or haplotypes with AD. © Springer-Verlag 2010.

Torbidoni A.V.,Pediatric Hospital | Laurent V.E.,Pediatric Hospital | Sampor C.,Pediatric Hospital | Ottaviani D.,Pediatric Hospital | And 7 more authors.
JAMA Ophthalmology | Year: 2015

IMPORTANCE: Disseminated retinoblastoma is usually fatal. Identification of small amounts (minimal dissemination [MD]) of tumor cells in extraocular sites might be a tool for designing appropriate treatments. OBJECTIVE: To test cone-rod homeobox (CRX) transcription factor as a lineage-specific molecular marker for metastatic retinoblastoma and for evaluation of MD. DESIGN, SETTING, AND PARTICIPANTS: In a prospective cohort design study, we evaluated CRX messenger RNA (mRNA) by retrotranscription followed by real-time polymerase chain reaction as a diagnostic test in samples obtained from bone marrow, peripheral blood, and cerebrospinal fluid (CSF) at diagnosis, after induction chemotherapy, and during follow-up. The study was conducted from June 30, 2008, to June 30, 2014. Seventeen retinoblastoma primary tumors, 2 retinoblastoma cell lines, and 47 samples of bone marrow from other cancers (controls) were studied. Seventeen patients with metastatic retinoblastoma (9 at diagnosis, 8 at relapse; age range: 18-41 months) were included. MAIN OUTCOMES AND MEASURES: Detection of CRX mRNA as a marker for metastatic retinoblastoma and MD in bone marrow and CSF and its correlation with clinical findings. RESULTS: Cone-rod homeobox mRNA was expressed in all tumors (relative expression levels range, 8.1 × 10-5 to 5.6) and cell lines. In control samples, there was no amplification of CRX; only the housekeeping gene (GAPDH) demonstrated amplification. Bone marrow metastatic cells showed expression of CRX mRNA in all 9 children presenting with metastasis at the diagnosis (relative expression levels, 6.0 × 10-5 to 0.67). After induction chemotherapy, no evidence of MD of tumor cells was seen in any of the 8 responding children since only GAPDH showed amplification. In the CSF of children who had a metastatic relapse, CRX mRNA detection was positive in 2 patients in whom no conclusive results were reached by immunocytology for disialoganglioside GD2. Minimal dissemination in the CSF was associated with a clinical relapse in 2 cases. No concomitant MD was evident in the bone marrow in any case. CONCLUSIONS AND RELEVANCE: These data suggest that CRX mRNA is a novel marker for retinoblastoma at extraocular sites. In this study among patients with bone marrow metastasis, there was a quick, complete, and sustained molecular response after induction chemotherapy. In all patients with secondary metastasis, CSF relapse occurred independently from the bone marrow, suggesting a sanctuary site. Copyright 2015 American Medical Association. All rights reserved.

Gomara M.J.,Unit of Synthesis and Biomedical Applications of Peptides IQAC CSIC | Fernandez L.,Unit of Synthesis and Biomedical Applications of Peptides IQAC CSIC | Perez T.,Unit of Synthesis and Biomedical Applications of Peptides IQAC CSIC | Ercilla G.,Immunology Service | Haro I.,Unit of Synthesis and Biomedical Applications of Peptides IQAC CSIC
Analytical Biochemistry | Year: 2010

The use of synthetic peptides of both structural and nonstructural proteins of GB virus C (GBV-C) has been studied for the development of new systems to diagnose infection caused by this virus. In an attempt to increase the antigenicity of linear peptide sequences, chimeric multiple antigenic peptides (MAPs) containing epitopes from E2, NS4, and NS5 GBV-C proteins have been synthesized. The synthetic constructs were evaluated by ELISA to establish whether the epitopes in chimeric branched peptides are more efficiently recognized by the specific antibodies compared to the monomeric linear sequences. Moreover, we have investigated the application of a commercial biosensor instrument for the detection of antibodies against the GBV-C in human serum samples. The results of the immunoassays reported in this work highlight the usefulness of synthetic tetrameric branched peptides containing sequences from envelope and nonstructural GBV-C proteins for the diagnosis of GBV-C infection. The potential clinical value of the MAP4(E2-NS5a) for the serodiagnosis of GBV-C infection was demonstrated, thus providing the basis for performing prevalence studies of the infection among the hemodialyzed and hepatitis C virus (HCV)-infected population. © 2009 Elsevier Inc. All rights reserved.

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