Search PubMed⌕ Search

Biomedical subjects

N Matamoros

Publications and source records attributed to N Matamoros.

At least 19 recordsLinked to original sources
PubMed2006

Elevated serum interleukin (IL)-12p40 levels in common variable immunodeficiency disease and decreased peripheral blood dendritic cells: analysis of IL-12p40 and interferon-gamma gene.

Common variable immunodeficiency disease (CVID) is a heterogeneous syndrome characterized by low immunoglobulin serum levels and recurrent bacterial infections. Several studies suggest that CVID patients have a polarized immune response towards a T helper type 1 phenotype (TH1). However, the factors causing the TH1 polarization remain to be determined in this disease. In the present study, serum interleukin (IL)-12, interferon (IFN)-gamma levels and the IL-12p40 and IFN-gamma gene were studied in CVID patients. Furthermore, we evaluate dendritic cells (DCs) compartment, myeloid dendritic cells (mDCs) and plasmocytoid dendritic cells (pDCs), which help to differentiate naive T cells preferentially into TH1 and TH2, respectively. The serum IL-12p40 subunit levels were increased significantly in CVID patients compared to healthy controls. We examined whether these elevated serum IL-12p40 levels are associated with IFN-gamma or IL-12p40 gene polymorphisms, or with new mutations in the IL-12p40 promoter gene. In our hands, no new mutations were found and gene polymorphisms frequencies in CVID patients were similar to the control population. In conclusion, the elevated serum levels of IL-12p40 found in our CVID patients were not related to these genetic variations. The DC compartment analysis did not show an imbalance between pDCs and mDCs, but revealed the presence of low numbers and percentage of both DC populations in CVID.

Blood Cell Count↗
PubMed2006

Mannose-binding lectin does not act as an acute-phase reactant in adults with community-acquired pneumococcal pneumonia.

The objective of this work was to study the role of mannose-binding lectin (MBL) and C-reactive protein (CRP) in pneumococcal pneumonia, to determine whether MBL acts as an acute-phase reactant and whether the severity of the disease correlates with MBL levels. The study comprised 100 patients with pneumococcal pneumonia. The pneumonia severity score was calculated and graded into a risk class of mortality (Fine scale). The MBL genotypes and the levels of MBL and CRP at the acute and recovery phases were determined. Fifty patients with the wild-type MBL genotype showed higher MBL levels in each phase (P < 0.001) and an increased risk to developing bacteraemia, odds ratio (OR) 2.74, 95% confidence interval (CI) 1.01-7.52) (P = 0.02), but this did not correlate with the pneumonia severity class. CRP levels in the acute phase, 79.53 mg/l [standard deviation (s.d.) 106.93], were higher in the subjects with positive blood cultures (P = 0.003), and remained higher [20.12 mg/l (s.d. 31.90)] in the group of patients with an underlying disease (P = 0.01). No correlation was observed between the levels of MBL and CRP in each phase, or with the pneumonia severity score. We cannot conclude that MBL acts uniformly as an acute-phase reactant in pneumococcal pneumonia. MBL levels do not correlate well with the severity of the pneumonia. The risk of developing bacteraemia could be enhanced in individuals with the wild-type MBL genotype.

Acute-Phase Reaction↗
PubMed2006

Costimulatory molecules and cytokine production by T lymphocytes in common variable immunodeficiency disease.

Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized by hypogammaglobulinaemia and recurrent infections. Although early works pointed to a primary B-lymphocyte defect as a cause of the disease, a failure in T-lymphocyte cooperation has also been suggested. T cells exert their costimulatory function through either membrane costimulatory molecules or secreted cytokines, both having an influence in the development of the humoral response. The aim of our study was to evaluate whether an abnormal expression and induction of costimulatory molecules or alterations in the production of cytokines by T cells cause deficient T/B cooperation in CVID patients. We studied the expression and upregulation of costimulatory molecules (CD28, CD40L/CD154 and CTLA-4/CD152) and production of cytokines (IL-2, IL-4, IL-6, IL-10, IFN-gamma and TNF-alpha) in purified T lymphocytes from CVID patients stimulated with optimal doses of anti-CD3 or suboptimal doses of anti-CD3 and anti-CD28. Stimulated T cells from CVID patients expressed normal levels of CD28, CD40L/CD154 and CTLA-4/CD152 when compared with controls. Except for higher production of IL-4 after stimulation with anti-CD3, T cells of CVID patients produced similar amounts of cytokines compared with controls. An imbalance between costimulatory molecules expression (CD28, CD40L/CD154 and CTLA-4/CD152) and cytokine production by T cells does not explain a deficient cooperation between T and B cells in this group of CVID patients.

Adult↗
PubMed2006

Allelic diversity and affinity variants of MICA are imbalanced in Spanish patients with Behçet's disease.

The aetiology of Behçet's disease (BD) is still unknown, but genetic and environmental factors are involved. HLA-B*51 is considered a susceptibility marker and some MICA alleles have also been associated. Cytotoxic T lymphocytes have been suggested as responsible for BD lesions by engaging MICA through NKG2D surface molecules. In the present study, HLA-B and MICA alleles were typed by polymerase chain reaction using sequence-specific primers, in 165 healthy Spanish controls and 42 BD patients. In the healthy group, MICA*008 (28.48%), MICA*004 (17.58%), MICA*002 (14.24%) and MICA*009 (9.39%) were the predominant alleles and the most common haplotype was MICA*004-B*44 (12.12%). MICA*001 (5.15%), MICA*004, MICA*011 (4.54%) and MICA*018 (5.15%) were more frequent, and MICA*010 (1.81%) and MICA*008 were less prevalent than in other Caucasoid populations. Similar results have been reported in North African individuals and this could support the hypothesis of a common ancestral origin of both populations. The frequencies of MICA*009 and MICA*019 were significantly increased in our BD patients in comparison with controls: 22.62% versus 9.39% and 10.71% versus 1.81% respectively. The increase of MICA*019 had not been described in other BD cohorts, and it corroborates the genetic heterogeneity at MICA locus in BD patients. High-affinity MICA alleles for NKG2D were more frequent in controls than in patients. Moreover, high-affinity alleles were not found in homozygous BD patients. These results argue against the hypothesis of an autoaggressive response in BD patients through MICA-NKG2D interactions.

Behcet Syndrome↗
PubMed2002

HLA polymorphism in a Majorcan population of Jewish descent: comparison with Majorca, Minorca, Ibiza (Balearic Islands) and other Jewish communities.

'Chueta' was the name given to the Catholic descendants of Jewish victims of the last Spanish Inquisition process in Majorca Island in the western Mediterranean. We have studied the allele distribution of HLA-A, -B, -Cw, -DRB1 and -DQB1 loci of 103 random, healthy, unrelated individuals belonging to the ancient Majorcan Jewish community, known locally as Chuetas, and 589 individuals from the Balearic population selected because of their typical Balearic - Majorca, Minorca or Ibiza - lineages and according to their ancestor's place of birth. Our aim was to establish the genetic relationship between Majorcan Chuetas, and Balearic and other Jewish and Mediterranean populations. Our results have shown that, to a remarkable extent, they have retained their biological identity, with a unique pattern, in terms of gene and haplotype frequencies, separate from the other populations of Majorca. The Chuetas were found to be more related to Moroccan and Libyan Jews than other Majorcans. Characteristic Jewish haplotypes, A26-B38-DRB1*13, A24-B38-DRB1*11, A1-B52-DRB1*15/16, were found in our study. Some peculiarities were observed in the distribution of common haplotypes among the three main Balearic Islands. The Ibizan population was genetically different from the other Balearic populations, with a high frequency of some haplotypes, for example, A29-Cw*16-B44-DRB1*07-DQB1*03; A1-Cw*07-B8-DRB1*03-DQB1*02. We also found a new haplotype, A25-Cw*12-B39-DRB1*11-DQB1*03(3.5%), in Ibizans and a more limited variability in the HLA alleles that were expressed, perhaps because of genetic isolation. The genetic diversity of the populations from Majorca and Minorca were similar and more related to the mainland Spanish population.

Alleles↗
PubMed2002

Risk factors in HIV-1-infected patients developing repetitive bacterial infections: toxicological, clinical, specific antibody class responses, opsonophagocytosis and Fc(gamma) RIIa polymorphism characteristics.

The aim of the study was to determine possible factors related to the risk of developing recurrent bacterial respiratory tract infections in HIV-1-infected patients, regardless of the degree of immune cellular impairment. Thirty-three HIV-1 seropositive patients with previous repetitive bacterial respiratory tract infections (case group), 33 HIV-1 seropositive controls (matched by CD4-cell counts) without these antecedents and 27 healthy controls were studied before and after administration of pneumococcal and Haemophilus influenzae type b vaccines. Clinical or toxicological variables, cutaneous tests, complement factors, beta2-microglobulin, serum IgM, IgA, IgG and subclasses, specific antibodies (IgG, IgG2, IgA) against pneumococcal vaccine and polyribosylribitol phosphate (PRP), their avidity, opsonophagocytosis and IgG(2)m and Fc(gamma)RIIa allotypes were determined. A history of drug abuse (P = 0.001), less likelihood of receiving high activity antiretroviral treatment high activity antiretroviral treatment (HAART) (P = 0.01), higher levels of HIV-1 viral load (P < 0.05), serum IgG (P < 0.01) and beta2-microglobulin (P < 0.01) were observed in the case group. Also, a lower increase in specific antibodies to pneumococcal vaccine and PRP was demonstrated in the cases in comparison with the two control groups. No differences were observed in the avidity of antibodies, opsonophagocytic capacity or IgG(2)m and Fc(gamma)RIIa allotypes between the three groups. These data indicate that vaccination strategies against encapsulated bacteria can be unsuccessful in the HIV-1-infected patients presenting repetitive bacterial respiratory tract infections if behavioural aspects or measures to improve adherence to HAART therapies are not considered.

AIDS-Related Opportunistic Infections↗
PubMed2001

Molecular studies and NK cell function of a new case of TAP2 homozygous human deficiency.

In this paper we describe the clinical and molecular features of a new case (GOR) of homozygous human TAP2 deficiency, analysing the phenotype and function of NK cells. The patient presented from infancy with recurrent sinopulmonary infections; a selective IgG2 deficiency, negative antibody response to polysaccharide vaccination and low level of cell surface expression of HLA class I antigens were found. The sequence of TAP2 gene identified a single mutation, a C to T substitution changing the CGA arg codon at amino acid 220 into TGA stop codon in exon 3. By using MoAbs for KIRs, CD94, CD94/NKG2A and ILT2 we observed, in agreement with others, that the latter two receptors were overexpressed on TAP2-deficient NK cells. The inhibitory CD94/NKG2A and triggering CD94/NKG2C NK receptors, specific for HLA-E, appeared to be functional in a limited number of NK clones that could be expanded in vitro. Expression of HLA-E was virtually undetectable in GOR B-LCL and very faint in PBMC, further supporting that interactions of class I leader sequence nonamers with HLA-E in the ER depend on a functional TAP complex.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

A novel nonsense mutation at Glu-631 in a Spanish family with complement component 7 deficiency.

Deficiency of the seventh component of complement (C7D) is frequently associated with recurrent neisserial infections. We report in the present study the genetic basis for C7D in a Spanish family. We used exon-specific polymerase chain reaction (PCR)/single-strand conformation polymorphism (SSCP) analysis as a screening step for mutations, followed by direct sequencing of the target exon. The mutation in the proband was a homozygous G-to-T transversion at nucleotide 1957, the first nucleotide of the codon GAG for Glu-631, leading to a stop codon TAG (E631X). Our result provides further evidence that the molecular pathogenesis of C7D is heterogeneous.

Adult↗
PubMed1999

CD95 expression and function on lymphocyte subpopulations in common variable immunodeficiency (CVID); related to increased apoptosis.

Apoptosis is now recognized as a central process of development and disease, and it has been proposed as one of the mechanisms that may account for the lymphopenia seen in some diseases. In this study we measured spontaneous apoptosis and CD95 expression on different cell subpopulations from CVID patients, using flow cytometric techniques. We divided our patients into two groups according to their CD4+ and CD4+CD45RA+ cell counts. Our results clearly show increased spontaneous apoptosis and CD95 expression on the CD4+ and CD4+CD45RA+ subsets from lymphopenic CVID patients compared with normal subjects and disease controls. Interestingly, our lymphopenic CVID patients presented a profound reduction in absolute counts, mainly affecting the CD4+CD45RA+ subpopulation. We also found a statistically significant direct correlation between absolute numbers of CD4+CD45RA+ T cells and spontaneous apoptosis on the same subset in CVID patients, but attempts to induce CD95-mediated apoptosis were unsuccessful despite increased CD95 expression on CD4+ T cells. These findings suggest that apoptosis could be one of the mechanisms implicated in the significant lymphopenia present in these patients.

Agammaglobulinemia↗
PubMed1999

Genetic linkage of hyper-IgE syndrome to chromosome 4.

The hyper-IgE syndrome (HIES) is a rare primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and highly elevated levels of serum IgE. HIES is now recognized as a multisystem disorder, with nonimmunologic abnormalities of the dentition, bones, and connective tissue. HIES can be transmitted as an autosomal dominant trait with variable expressivity. Nineteen kindreds with multiple cases of HIES were scored for clinical and laboratory findings and were genotyped with polymorphic markers in a candidate region on human chromosome 4. Linkage analysis showed a maximum two-point LOD score of 3.61 at recombination fraction of 0 with marker D4S428. Multipoint analysis and simulation testing confirmed that the proximal 4q region contains a disease locus for HIES.

Chromosome Deletion↗
PubMed1998

Small cytoplasmic antigens from Pseudomonas aeruginosa stimulate gammadelta T lymphocytes.

Gammadelta T lymphocytes respond to different bacterial antigens and transformed cells. The antigenic molecules responsible for this activity have been studied extensively in antigenic preparations from Mycobacterium. We describe here the in vitro effect of Pseudomonas aeruginosa on gammadelta T lymphocytes and the properties of the implicated compounds. We found a preferential gammadelta T-cell expansion when we used heat-treated P. aeruginosa preparations and a dose-dependent inhibition of proliferation of peripheral blood mononuclear cells (PBMC) when non-heat-treated antigens were studied. This expansion corresponded to a Vgamma9-positive subpopulation. In contrast to alphabeta T lymphocytes, the highest stimulatory activity was restricted to very small cytosolic compounds. This activity was protease resistant and phosphatase sensitive and always dependent on interleukin (IL)-2 or alphabeta T-cell activation. We concluded that the antigenic molecules from P. aeruginosa that activated gammadelta T lymphocytes were small, non-peptidic, phosphorylated compounds, similar to those previously described from Mycobacterium.

Adult↗
PubMed1996

Cryopreservation of hematopoietic progenitor cells with 5-percent dimethyl sulfoxide at -80 degrees C without rate-controlled freezing.

BACKGROUND: Cryopreservation of hematopoietic cells with the rate-controlled method is used in the majority of centers. In recent years, there has been a trend toward the simplification of the process. STUDY DESIGN AND METHODS: A simplified method for cryopreservation was developed with 5-percent dimethyl sulfoxide (DMSO) as the sole cryoprotectant without rate-controlled freezing. Experiments were done with progressive concentrations of DMSO, ranging from 0 to 10 percent. With DMSO concentrations from 5- to 10-percent, the best recovery and viability for hematopoietic progenitor cells were observed. Hematopoietic progenitor cells with plasma and 5-percent DMSO were frozen and stored in a -80 degrees C mechanical freezer. Ten patients with solid and hematologic malignancies underwent transplantation with autologous hematopoietic progenitor cells. RESULTS: The median number of transfused mononuclear cells and CD34+ cells was 3.70 (3.1-8.2) x 10(8) per kg and 1.70 (0.8-6.5) x 10(6) per kg, respectively. The median number of transfused colony-forming units-granulocyte-macrophage was 12.45 (3.4-55.3) x 10(4) per kg. All patients showed rapid and sustained engraftment. The mean times to reach a neutrophil count of 0.5 x 10(9) per L and a platelet count of 50 x 10(9) per L were 11.50 +/- 1.70 and 13.90 +/- 3.98 days, respectively. All patients are alive and without transfusion requirements in complete remission 2 to 8 months after transplantation. CONCLUSION: This simplified cryopreservation technique will be useful for institutions without rate-controlled freezing facilities. Moreover, this method diminishes the amount of DMSO infused to patients, as well as its toxicity.

Adolescent↗
PubMed1995

Alterations in interleukin secretion (IL-2 and IL-4) by CD4 and CD4 CD45RO cells from common variable immunodeficiency (CVI) patients.

The failure of B cells from CVI patients to secrete normal amounts of antibodies has been attributed either to an intrinsic B cell defect or to a lack of cooperation from T cells. In an attempt to improve the definition of the origin of this defect in one of the main cellular compartments, we studied the ability of helper CD4 cells and their CD4 CD45RO subpopulation from CVI patients to secrete interleukins (IL-2 and IL-4) in response to mitogen stimulation. We found that CD4 and CD4 CD45RO cells from some patients secrete abnormal amounts of interleukins (in general low levels of IL-2 and high levels of IL-4) upon stimulation with pokeweed mitogen (PWM). These irregularities may contribute to the defective differentiation of B cells in these patients.

Adolescent↗