Systemic lupus erythematosus (SLE) patients exhibit alterations in cytokine production that may be relevant to SLE pathogenesis. There is evidence that cytokine gene polymorphisms control cytokine production; thus, these polymorphisms may be associated with SLE or its clinical manifestations. To establish the association of tumor necrosis factor alpha (TNF-alpha), transforming growth factor (TGF) beta1, interleukin (IL)-10, and IL-6 gene polymorphisms in Colombian SLE patients and their clinical manifestations, 120 SLE patients and 102 healthy controls were studied. Single nucleotide polymorphisms were studied by sequence-specific primers polymerase chain reaction (SSP-PCR) at: TNFalpha-308 (G/A), TGFbeta1 codon 10 (C/T) and codon 25 (G/C), IL-10 -1082 (G/A), -819 (C/T) and -592 (C/A), and IL-6 + 174 (G/C). Human leukocyte antigen (HLA)-DRbeta1 was typed by SSP-PCR. SLE patients had increased frequency of allele C at TGFbeta1 codon 25 (P = 0.0001, odds ratio (OR): 4.25, 95% confidence interval (CI): 2.17-8.35) and allele A at TNFalpha-308 (P = 0.0004 OR: 3.9, 95% CI: 1.65-5.80) compared with healthy controls. There was higher frequency of GC genotype at TGFbeta1 codon 25 in SLE patients (P < 0.0001). Extended genotypic analysis showed that SLE patients have decreased frequency of TNFalphaLow/TGFbeta1High (0.50) compared with healthy controls (0.80) (P < 0.0001). No association was found between these polymorphisms and SLE clinical manifestations except for Sm and Ro autoantibodies that were associated with TNFalpha allele A. There is an association between TNFalpha-308A/TGFbeta1 codon 25C with SLE susceptibility in Colombian population. This association may result in a highly inflammatory response with a decrease regulatory function mediated by TNFalpha and TGFbeta1, respectively. The TNFalpha-308A/TGFbeta1 25C genotype may be one component of genetic susceptibility to SLE in Colombian population.
The mechanisms underlying long-term acceptance of kidney allografts in humans under minimal or no maintenance immunosuppression are poorly understood. We analyzed the T-cell receptor (TCR) repertoires in circulating T cells of patients with long-term (≥9 years) renal allograft survival with (LTS-IS) and without immunosuppression (LTS-NoIS). T cells of LTS patients exhibited strongly altered TCR Vß usage, including an increased frequency of oligoclonality and a decreased frequency of polyclonality. All 3 LTS-NoIS and 12 of 16 LTS-IS patients demonstrated oligoclonality in at least three or more TCR Vß families, and the frequency of oligoclonality in these patients was significantly higher as compared to patients with well-functioning grafts at 3 years (p < 0.005 both), an uncomplicated course during the first year (p < 0.0001, both), acute rejection (p < 0.0001, both), chronic allograft nephropathy at 7 (p < 0.0001, both) or 13 years (p < 0.0001, both), dialysis patients (p < 0.0001, both) or healthy controls (p < 0.0001, both). In contrast to LTS patients, all other studied patient groups exhibited a polyclonal TCR repertoire. Our data indicate that TCR alteration is a common feature of long-term allograft outcome, which might be explained by clonal deletion, exhaustion of alloreactive T cells or predominant expression of particular T-cell subpopulations, such as regulatory T cells.
A significant association between HFE gene mutations and the HLA-A*03-B*07 and
HLA-A*29-B*44 haplotypes has been reported in the Spanish population. It has been
proposed that these mutations are probably connected with Celtic and North African
ancestry, respectively. We aimed to find the possible ancestral association between
HLA alleles and haplotypes associated with the HFE gene (C282Y and
H63D) mutations in 214 subjects from Antioquia, Colombia. These were 18 individuals
with presumed hereditary hemochromatosis (“HH”) and 196 controls. The HLA-B*07 allele
was in linkage disequilibrium (LD) with C282Y, while HLA-A*23, A*29, HLA-B*44, and
B*49 were in LD with H63D. Altogether, our results show that, although the H63D
mutation is more common in the Antioquia population, it is not associated with any
particular HLA haplotype, whereas the C282Y mutation is associated with
HLA-A*03-B*07, this supporting a northern Spaniard ancestry.
The scientific literature (mainly psycho-pedagogical) on the child's play is immense and epistemologically recognized, but the same cannot be said about the use of play in emergency situations (natural, humanitarian, social, political). Few researches exist on this subject, especially focused on children with disabilities. The paper analyses the situation of children (with and without disabilities) in natural and man-made disasters and of the attention given to this vulnerable population within academic researches and humanitarian programmes. Then, this article reflects on the pedagogical value of the role and the use of play in crisis situations for all the children. In particular, starting from a narrative review of the academic literature and research in area, it aims at proposing a preliminary overview of the different play-based interventions promoted worldwide in such emergencies.
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