Biomedical subjects

A Blanco-Quirós

Publications and source records attributed to A Blanco-Quirós.

16 recordsLinked to original sources

PubMed2006

Interleukin 18 maintains a long-standing inflammation in coeliac disease patients.

Dietary gluten induces an early response in the intestine of coeliac disease patients (CD), within a few hours, and this is driven by high levels of proinflammatory cytokines, including IFNgamma and IL-15, as has been thoroughly shown by gluten stimulation of biopsy explants. Our aim was to identify the immune mediators involved in the long-standing inflammation in untreated CD patients at diagnosis. mRNA and protein levels of TNFalpha, IL-12(p35), IL-12(p40), IL-15, IL-18 and IL-23(p19) were quantified in biopsies from active CD patients, CD patients on a gluten-free diet (GFD), healthy controls, and patients with non-CD inflammation and mild histological changes in the intestine. Biopsies from CD patients on a GFD were also stimulated in vitro with gliadin, and protein expression of IL-15 and IL-18 was analysed. Levels of IL-12 and IL-23 mRNA are nearly absent, and TNFalpha levels remain unchanged among different groups. Both the active and inactive forms of IL-18 protein have been found in all samples from active CD, and protein expression was only localized within the crypts. Levels of IL-15 mRNA remain unchanged, and protein expression, localized within the lamina propria, is found in a small number of samples. In vitro stimulation with gluten induces the expression of IL-15 and IL-18. In active CD, the early response following gluten intake characterized by high IFNgamma levels is driven by IL-18, and probably IL-15, and this alternates with periods of long-standing inflammation with moderate IFNgamma levels, maintained by IL-18 alone.

Adolescent↗

PubMed2005

[Geographic variation in the prevalence of asthma symptoms in Spanish children and adolescents. International Study of Asthma and Allergies in Childhood (ISAAC) Phase 3, Spain].

OBJECTIVE: To analyze geographic variations in the prevalence of symptoms related to asthma in Spanish children and adolescents. POPULATION AND METHODS: In 2001 and 2002, the Spanish arm of the International Study of Asthma and Allergies in Childhood (ISAAC) Phase 3 collected information on 28 445 children in the age bracket of 6-7 years in 10 metropolitan areas (A Coruña, Asturias, Barcelona, Bilbao, Cartagena, Castellón, Madrid, Pamplona, San Sebastián, and Valencia) and on 31 257 adolescents in the bracket 13-14 years in 11 areas (the previously named areas plus Valladolid). An asthma symptom questionnaire was filled in by parents or the adolescents themselves. Differences in symptoms between geographic areas were analyzed by fitting a logistic regression model. The relationship between symptoms and age was analyzed by linear correlation. RESULTS: The prevalence of recent wheezing (last 12 months) ranged from 7.1% to 12.9% among 6-7-year-olds and from 7.1% to 15.3% among the 13-14-year-olds. The greatest risk of recent wheezing was observed for children in A Coruña (odds ratio [OR] =1.96 in comparison with the area of lowest prevalence; 95% confidence interval [CI], 1.65-2.33) and Bilbao (OR=1.83; 95% CI, 1.54-2.18) and for adolescents in A Coruña (OR=2.38; 95% CI, 2.04-2.79) and Asturias (OR=2.37; 95% CI, 2.03-2.77). A strong correlation (r=0.72) was observed between the prevalence of recent wheezing and age in each of the geographic areas. CONCLUSIONS: Considerable geographic variation in the prevalence of asthma symptoms can be seen in Spain even among young children. Symptoms are more frequent in children and adolescents who live on the Spain s northern Atlantic coast.

Adolescent↗

PubMed2002

Influence of leptin levels and body weight in survival of children with sepsis.

UNLABELLED: High levels of serum leptin (LPT) were reported in adult patients with sepsis and a protective role was suggested. LPT was determined in sera from 55 children with severe sepsis at admission (0 h), 6, 24 and 48 h. LPT levels were higher at 0 h than at 24 h (2.80 vs 1.61 ng/ml; p = 0.009) and a negative correlation was found with IL-13 (p = 0.009), and granulocyte counts (p = 0.035), but not with other factors. Infants younger than 12 mo of age had higher LPT levels than older infants (5.88 vs 2.38 ng/ml; p = 0.0005). The increase in LPT levels was higher in non-survivor patients than in survivors, with a maximum difference at 24 h (5.30 vs 1.45 ng/ml; p = 0.0042). However, LPT levels were not associated with shock, multiorgan failure or the severity score. Children who died showed higher percentiles of weight than survivors (p = 0.025). A subgroup with higher LPT (> Pc75) included mainly patients with weight > Pc50 (p = 0.0065), low IL-13 levels (p = 0.007) and low granulocyte counts (p = 0.013), Neisseria meningitidis B being the most frequently isolated germ (p = 0.022). CONCLUSION: Using a model of severe infection, mainly meningococcal, in young children (median 3 y 6 mo old), it was not possible to confirm previous results in adults. A general protective role for LPT in sepsis seems unlikely.

Adolescent↗

PubMed2001

Susceptibility genes for asthma and allergy: hits and questions.

Allergy and asthma are closely related conditions which result from a complex interaction between several genetic and environmental factors. On the basis of familial linkage analysis data from different populations, some chromosomal regions containing a series of susceptibility loci have been identified. To date, genome-wide search studies have reported a group of chromosomal regions which include most likely several candidate genes for asthma and allergy. Some of these genes are excellent candidates, as they are known to modulate the immune response and airways inflammation processes. So, by focusing efforts on the analysis of those chromosomal regions, the characterization of the potentially important genes can be achieved. This will undoubtedly provide a clue for a better understanding of those pathologic components involved in the onset and development of asthma and allergic disorders.

Asthma↗

PubMed2000

The HLA-DRB4 gene is present in half of the Spanish HLA-DQ2-negative celiac patients.

We studied nine consecutive DQ2-negative celiacs [from a group of 186 consecutive celiac disease (CD) patients] for the presence of the HLA-DQB1, DRB1, and DRBx alleles. HLA-DR53 was present in only 5 out of 9 (55%) of DQ2-negative patients. DRB4 (DR53) positivity -39% of chromosomes--among Spanish DQ2-negative CD patients is due to both DR4- and DR7-positive cases. Spanish DQ2-positive patients show a high frequency of DR7/DR11 heterozygous carriers of DRB4 (DR53). One-third of our DQ2-negative celiac patients have DRB1*04 (DR4). Six patients are DR4 negative: at least one of the DQ2 alleles (DQA1*0501/DQB1*02) is present in four cases, but none of the alleles of risk, including DR53, were found in the remaining two cases, both of whom carry DQB1*06 alleles (*0602/3 and 0604). The fact that half of our DQ2-negative patients lack DRB4 (DR53) leads us to believe that this gene is not an essential factor to confer CD susceptibility.

Alleles↗

PubMed2000

Cord blood interleukin-10 levels are increased in preterm newborns.

UNLABELLED: Cell-mediated immunosuppression due to interleukin (IL)-10 may contribute to normal pregnancy. By contrast, delivery is associated with a predominance of T-helper-1 (Th1) cytokines (IL-12, interferon-gamma) and might be regarded as a graft rejection process. The aim of the study was to assess IL-10 and IL-12 levels in cord blood samples from newborns and their normal mothers in relation to the gestational age and type of delivery. Cord blood and serum samples were obtained from 31 term newborns (gestational age 38-42 weeks) and 40 preterm newborns (mean gestational age 32 weeks). Serum samples were obtained from 26 mothers of term newborns at birth. There were 18 term and preterm infants born by caesarean section. Measurements of IL-10 and IL-12 levels by ELISA were repeated in mothers 15 days after delivery and in 11 preterm infants (median 14 days of age). Cord blood IL-10 levels were significantly higher in preterm than in term newborns (median 17.0 versus 3.2 pg/ml, P = 0.0001), but were similar to term newborns and paired mothers (2.2 versus 1.0 pg/ml). Term and preterm newborns also showed similar cord blood IL-12 levels (median 349 versus 320 pg/ml), and these levels were significantly higher when compared to their paired mothers (median 14.5 pg/ml, P = 0.0003). Cord blood IL-10 levels showed a significant inverse correlation with gestational age (P = 0.0001). When preterm infants, at several weeks post-delivery, were compared to gestational age matched newborns, their IL-10 levels were similar (median 8.3 pg/ml) whereas IL-12 levels were clearly lower (147 pg/ml; P = 0.0007). The type of delivery (vaginal versus caesarean) did not influence cord blood IL-10 and IL-12 results. CONCLUSION: Cord blood IL-10 levels are increased in preterm newborns and may be due to the immunosuppression occurring during pregnancy and to fetal immaturity because these levels are inversely correlated with gestational age.

Female↗

PubMed1999

Decreased interleukin-12 levels in umbilical cord blood in children who developed acute bronchiolitis.

Respiratory syncytial virus (RSV) infection is common in young children, but only a few develop severe bronchiolitis. The relationship between bronchiolitis, asthma, and atopy has been debated for a long time, but the pathogenesis of wheezing remains unclear. A Th1 and Th2-type lymphocyte imbalance seems to be involved in asthma and atopic disease. Serum interleukin-12 (IL-12), IL-10, and soluble CD30 (sCD30) levels were measured by enzyme-linked immunosorbent assay (ELISA) in 23 cord blood samples kept frozen since birth: 11 from normal term newborns who several months later were admitted to the hospital with bronchiolitis, and 12 from newborns who did not develop the disease (controls). The study was also performed on 28 additional children (1-16 months old) suffering an episode of acute bronchiolitis. IL-12 was clearly increased in all cases at birth, but newborns who later developed bronchiolitis showed low IL-12 levels in cord blood compared to newborns who did not develop the disease (median 295 vs. 507 pg/mL; P = 0.001). sCD30 levels were also decreased in the first group (15 vs. 26 U/mL; P = 0.007). During episodes of bronchiolitis, a clear rise of IL-12, IL-10, and sCD30 was observed. None of the factors studied in the acute phase showed statistical differences in children who were later readmitted to the hospital due to repeated wheezing crises. Children who develop acute bronchiolitis with wheezing may have an immunological imbalance that is expressed at the time of delivery by a lower concentration of serum IL-12.

Acute Disease↗

PubMed1998

Alpha-1 antichymotrypsin levels are actively increased in normal colostrum.

BACKGROUND: It is well known that human colostrum has important antiinflammatory functions. The purpose of the current study was to determine antiprotease levels in colostrum and serum and to assess the importance of local synthesis and the electrophoretic differences in both locations. METHODS: Five protease inhibitors were determined by radical immunodiffusion in colostrum and serum samples taken simultaneously from 50 healthy women, 36 to 72 hours after delivery. RESULTS: Antithrombin II, inter-alpha trypsin inhibitor, and alpha-2 macroglobulin levels were undetectable in colostrum. Mean antitrypsin levels in colostrum were 6% of serum levels, but colostrum alpha-1 antichymotrypsin was higher than expected (0.39+/-0.34 g/l) in relation according to the albumin passive transport, and their mean value was 41% of serum levels. Colostrum antichymotrypsin levels did not correlate with serum antichymotrypsin levels or with colostrum albumin levels. The antichymotrypsin molecule in colostrum had a slower electrophoretic mobility when compared with that of serum antichymotrypsin, and it showed a different pattern in Western blot analysis, with a predominating 80-kDa molecule. CONCLUSIONS: Although the origin of colostral antichymotrypsin is unclear, local production in breast epithelial cells is likely. Antichymotrypsin is increased in colostrum, and its molecule has some characteristic differences, suggesting that it has an important and specific role in infant nutrition during breast milk feeding.

Colostrum↗

PubMed1998

Lack of association between atopy and RsaI polymorphism within intron 2 of the Fc(epsilon)RI-beta gene in a Spanish population sample.

BACKGROUND: The B genotype of RasI polymorphism located within intron 2 of the Fc-IgE receptor I (Fc(epsilon)RI) gene was previously found to be increased in atopic patients from a Japanese population sample. METHODS: We studied these A/B genotypes in 70 Spanish atopic patients, and the results were compared to those of 51 nonatopic controls. RasI polymorphisms were studied by specific digestion of polymerase chain reaction fragments followed by polyacrylamide gel electrophoresis. RESULTS: The polymorphism frequency (A/A: 25/70, A/B: 28/70, B/B: 17/70) found in patients did not differ from the frequency in nonatopic control subjects. CONCLUSIONS: We did not find RasI polymorphisms associated with atopic disease. The genetic findings in atopy and asthma may be very different according to ethnic and local characteristics, and they must be carefully verified in different population samples.

Adolescent↗

PubMed1997

Lack of correlation between soluble CD14 and IL-6 in meningococcal septic shock.

Meningococcal sepsis is a good model to study the dynamic response of cytokines and other soluble factors in vivo in the early stages of the disease. Levels of soluble CD14, interleukin-6 (IL-6), IL-6 receptor (IL-6R), and C-reactive protein (CRP) have been measured in plasma from 26 children with septic shock (nine of whom had disseminated intravascular coagulation) and from ten control children. All samples were collected at the onset, before treatment, and, when possible, 24 and 48 hours later. At admission, patients had significantly higher levels of IL-6 (p < 0.001) and CRP (p < 0.001), and lower levels of IL-6R (p < 0.005) than normal controls. After 24 hours, there was a significant increase of sCD24 (p < 0.05) and CRP (p < 0.001). Although IL-6 showed a progressive decline since the onset, its levels were always higher than controls. There was an inverse correlation between IL-6 and both IL-6R (p < 0.001) and CRP (p < 0.001), probably due to the later increase of CRP. Nevertheless, sCD14 did not correlate with IL-6 levels. We have confirmed the finding of IL-6 as a sensitive and reliable inflammatory marker in septic shock. Moreover, the ratio IL-6/IL-6R may have a prognostic value, given a putative role of IL-6R in modulating the effects of IL-6 in meningococcal sepsis.

Bacteremia↗

PubMed1997

HLA-DQA10501 and DQB102 homozygosity and disease susceptibility in Spanish coeliac patients.

Coeliac disease (CD) susceptibility is strongly associated with HLA-DQA1*0501 and DQB1*02 alleles. There are discordant reports on whether homozygosity increases the risk. We genotyped HLA-DQA1*0501 and DQB1*02 in 50 CD patients, 100 parents, and 50 controls. Most patients (96%) were positive for DQA1*0501 (RR = 18.07, p < 0.001), 94% for DQB1*02 (RR = 17.55, p < 0.001), and 92% for both alleles together (RR = 31.82, p < 0.001). DQA1*0501 was found in 52% of controls, DQB1*02 in 44%, and only 24% had both alleles. Patients homozygosity or heterozygosity was estimated by assessing-in each case-whether one or both parents were carriers of the allele of risk. The frequencies of parents both positive for DQA1*0501 (58%) and for DQB1*02 (53.1%) were higher than expected by the fact that the proband is a carrier. These findings suggest that the frequency of homozygosity is increased among CD patients, and therefore, homozygosity for either DQA1*0501 or DQB1*02 represents a risk factor added to the fact of being a carrier.

Alleles↗

PubMed1994

Monoclonal antibody-standardized cat extract immunotherapy: risk-benefit effects from a double-blind placebo study.

Twenty-eight patients (14 in an active treatment group and 14 in a placebo group) with rhinoconjunctivitis and asthma caused by cat hypersensitivity took part in a placebo-controlled, randomized, double-blind study to evaluate the risk-benefit quotient of the maintenance dose corresponding to 13.2 micrograms Fel d I antigen. The cat extract was biologically standardized and quantified with monoclonal antibodies (100 biological units: 33 microgram of Fel d I antigen, 650 micrograms of albumin, and 99 micrograms of Fel d Bd/K30 antigen). After 1 year of treatment, the systemic reactions to cat extract immunotherapy were mild and infrequent. Improvement was observed in the active treatment group in comparison with the placebo group in the medication-symptoms score (p < 0.001); in skin prick test (p < 0.001), conjunctival provocation test (p < 0.001), and allergen bronchoprovocation test (p < 0.05) results, and in nonspecific bronchial hyperreactivity measured with methacholine, which was not statistically significant. This study demonstrates the favorable risk-benefit quotient of the dose of 13.2 micrograms of Fel d I antigen, which may serve as a future reference in defining the optimum dose and appropriate proportion of antigens that should be administered in cat extract immunotherapy.

Adolescent↗

PubMedDate not supplied

High cord blood IL-10 levels in preterm newborns with respiratory distress syndrome.

BACKGROUND: The development of respiratory distress syndrome (RDS) is closely related to fetal immaturity, although the participation of inflammatory mechanisms also seems to be likely. We previously reported high interleukin-10 (IL-10) levels in cord blood from preterm infants. In the present study, we investigate the possible role of IL-10 and IL-12 in preterm newborns with RDS, a disease that is also closely related to gestational age. PATIENTS AND METHODS: Cord blood levels of IL-10 and IL-12 (p70 + p40) were determined by ELISA in 20 preterm infants who later developed RDS, in 21 preterm infants without RDS and in 31 full term newborns. In 11 patients follow-up samples could be also obtained between 2 and 14 days of life. RESULTS: Preterm infants with RDS showed higher IL-10 (27 vs 10.8 pg/mL; p: 0.0003) and lower IL-12 (188 vs 384; p: 0.002) levels in cord blood than premature infants without RDS and full term newborns (IL-10: 3.2 pg/mL, p: 0.0001; IL-12: 352 pg/mL; p: 0.002). The differences remained statistically significant after correction for the effect of gestational age between both preterm groups. CONCLUSIONS: The results obtained may be related to an immature cytokine response in premature infants, but the IL-12/IL-10 imbalance found in our patients also supports the hypothesis that inflammation plays a role in RDS.

Biomarkers↗

PubMedDate not supplied

IL6, IL10 and TGFB1 gene polymorphisms in coeliac disease: differences between DQ2 positive and negative patients.

UNLABELLED: Predisposition to coeliac disease (CD) might be partially due to an individual pattern of hyper-inflammatory biased immune response. One of these patterns of intense response may be linked to the haplotype carrying HLA-DQ2 alleles and TNF -308A allele. However, 10 % of CD patients do not express the DQ2 heterodimer and these do not usually carry the TNF -308A allele. A similar response might be achieved by genes codifying other cytokines. OBJECTIVES: To study biallelic polymorphisms in genes codifying for TNFalpha, IL10, IL6 and TGFbeta1 in DQ2 negative CD patients and to compare the results with DQ2 positive patients and healthy controls, in order to establish whether any of these polymorphisms have a role in CD susceptibility. METHODS: TNF -308 (G > A), IL-6 -174 (G > C) and TGFB1 codon 10 (+ 869, T > C) and codon 25 (+ 915, G > C) polymorphisms and IL-10 haplotype of polymorphisms in positions -1082 (G > A), -819 (C > T) and -592 (C > A) were typed by a SSP-PCR technique. RESULTS: The distribution of allele frequencies for TNF -308 is different between DQ2 positive CD patients and controls and the same occurs for haplotype frequencies of the IL10 promoter (-1082, -819, -592): The frequencies of the TNF -308A allele (p = 0.027), TNF -308A carriers (p = 0.031) and of IL10GCC haplotype are increased (p = 0.013) in DQ2 positive CD patients. However, the IL6 -174 allele G is more frequent in DQ2 negative patients than in healthy controls (p = 0.018), DQ2 negative controls (p = 0,018), and DQ2 positive patients (p = 0.008). CONCLUSIONS: DQ2 negative CD patients show an increased frequency of genotypes associated to IL6 high production. These were mainly allele G homozygous for the IL6 gene (-174) polymorphism. The IL6 -174GG genotype (homozygous) may be an additional risk marker for CD in DQ2 negative patients, representing an alternative susceptibility factor for CD when TNF -308A is negative.

Alleles↗

PubMedDate not supplied

Common variable immunodeficiency. Old questions are getting clearer.

Common variable immunodeficiency (CVID) is a heterogeneous entity characterized by an impaired ability to produce antibodies. The failure is localized in partially mature B lymphocytes, though T lymphocyte abnormalities are occasionally present. This deficiency affects antibody synthesis and class switch from IgD and IgM, to IgG and IgA. CVID is related to selective IgA deficiency, and both abnormalities may coincide in one same family, and evolve from one to another in the same patient. The symptoms generally manifest in adults, but can occur at any age, even in infancy. Recurrent bacterial infections or pneumonias are frequent, and may be complicated by gastrointestinal problems, granulomas, autoimmune disorders or malignancies. A defect in memory B cells seems to condition the clinical severity. Recently, several mutations in genes encoding for molecules (CD19, TACI, ICOS) involved in B cell survival and isotype switch have been identified in patients with CVID. Nevertheless, genetic abnormalities have been found in less than 25 % of cases with CVID; the underlying mechanism thus remains unknown in the majority of CVID patients, and research in this field must continue.

Adult↗

PubMedDate not supplied

Increased TNFA2, but not TNFB1, allele frequency in Spanish atopic patients.

Tumor necrosis factor (TNF) is a potent proinflammatory cytokine involved in asthma and atopy. Increased TNF-alpha levels have been found in airway biopsies and bronchoalveolar lavage fluids from asthmatic patients. Constitutional variations in the TNF-alpha secretion levels in vitro are associated with molecular polymorphisms located within and around the TNF loci. Our study objective was to investigate the association between atopy and two described di-allelic polymorphisms in the TNF locus: a G to A transition at position -308 in the 5'-promoter region of the TNFA gene (TNFA*1 and TNFA*2 alleles) and an Ncol restriction fragment length polymorphism (RFLP) in the first intron of the TNFB gene (TNFB*1 and TNFB*2 alleles). The genetic study was performed in 65 unrelated atopic patients and 60 healthy controls. The regions of interest were amplified from genomic DNA using specific primers and polymerase chain reaction. SSP-PCR analysis for TNFA -308 polymorphism genotyping and endonuclease digestion analysis for the TNFB Ncol RFLP were used. The frequency of the TNFA*2 allele was significantly higher in atopic subjects compared to the control group (38.5% vs. 10.5%; chi2 = 32.06; p <0.0001). The TNFA*2 allele is associated with a higher risk for the development of atopy (risk ratio = 9.44; EF = 0.65; chi2 = 30.06 p <0.0005). On the other hand, no significant association between the TNFB alleles and atopy was found. In conclusion, the TNFA*2 allele could be also a genetic risk marker for the predisposition to atopy in our population, as has been reported in other studies. Either the TNFA gene itself or a linked gene on chromosome region 6p21, which has yet to be identified, is a candidate gene for susceptibility to atopy.

Adolescent↗