Functional dysregulation of dendritic cells in patients with papular urticaria caused by fleabite

Q11415-1419Papular urticaria is a chronic allergic disease caused by fleabite. The presence of eosinophils, predominance of CD4-positive T cells in lesions, and IgE response suggest a Th2 immune response to flea proteins in patients with papular urticaria caused by fleabite (PUFB). Although PUFB is defined as an allergic reaction, the immunological mechanisms and the role of dendritic cells (DCs) have not been established. OBSERVATIONS: Flea body extract did not induce the maturation of monocyte-derived DCs in 10 patients with PUFB and in 10 healthy children. Simultaneous exposure of DCs to flea extract and lipopolysaccharide induced increased expression of CD83 (P < .01), CD86 (P < .01), and HLA-DR (P < .05), which was statistically significantly greater in patients' cells. Dendritic cells from patients stimulated with lipopolysaccharide secreted less interleukin 6 (IL-6) and IL-10 than DCs from control subjects. CONCLUSIONS: Results of this study indicate that the involvement of DCs in an immune response produced in the disease is mediated through the altered expression of membrane molecules. This may be related to constitutive impairment in the production of regulatory cytokines such as IL-6 and IL-10 in these patients

Association of Interleukin 10 (IL-10) gene promoter region polymorphisms with Flea Bite Papular Urticaria

Objetivos. Establecer si los polimorfismos en la región promotora del gen de la IL-IO localizados en las posiciones -819 y -592 están asociados con la urticaria papular causada por la picadura de pulga, en pacientes pediátricos que asistieron a consulta de alergia o de dermatología a la Fundación Santa Fe de Bogotá, Colombia. Métodos. La frecuencia de estos dos polimorfismos en el ADN fue analizada en 25 niños con urticaria papular y 22 controles por medio de PCR (Polymerase Chain Reaction') y RFLP (Restriction Fragment Length Polymorphisms). Resultados. No hubo diferencias significativas entre las frecuencias alélicas y genotípicas de cada polimorfismo individual o SNP (-819 o -592) entre pacientes y controles (p=0,21, OR= 1,87, IC95% 0,79-4,40) cuando fueron calculados por la prueba exacta de Fisher. Conclusiones. Aunque en este trabajo preliminar no se encontró asociación de los polimorfismos reportados en otras poblaciones con la enfermedad alérgica, hay una tendencia en nuestros experimentos a encontrar un mayor número de haplotipos AT en pacientes que en controles. Los resultados publicados por nuestro grupo de investigación, en cuanto a que la secreción de 1L-10 in vitro se encuentra disminuida en pacientes con urticaria papular y no en controles sanos, indicarían que la expresión genética de esta citocina estaría alterada en pacientes y, por consiguiente, esta condición estaría exacerbando la enfermedad. Los niveles disminuidos de esta citocina reguladora permitirían el desarrollo de condiciones hiperinmunes, como la alergia y la autoinmunidad.Artículo original275-283Objectives: In this study we aimed to establish whether IL-10 promoter region genetic polymorphisms in positions -819 and -592 were associated with papular urticaria caused by flea bite in pediatric patients from the Fundación Santa Fe de Bogotá, Colombia. Methods: The frequency of these DNA polymorphisms was analyzed in 25 infants suffering papular urticaria and 22 healthy controls, after amplification of their corresponding DNA through polymerase chain reaction (PCR) and further analysis of resulting restriction fragment length polymorphisms (RFLP). Results: We found no significant differences in allelic and genotypic frequencies of either -819 or -592 SNPs between patients and healthy controls (p=0.21, OR=1.87, 95% IC=0.79-4.40). Conclusions: Although we did not find in this preliminary study a genetic association between papular urticaria and previously reported allergy-associated SNPs such as -819 and -592, we found higher numbers of allergy-associated AT haplotypes in patients than in controls. Previously published results from our group showed in vitro a diminished IL-10 secretion in patients and not in healthy controls. This finding, together with our present results, would indicate that the genetic expression of this cytokine could be altered in patients and that this condition could determine the exacerbation of papular urticaria. Low levels of this cytokine would allow for the development of hyperimmune conditions such as allergy and autoimmunity

Monocyte-derived dendritic cells from chagasic patients vs healthy donors secrete differential levels of IL-10 and IL-12 when stimulated with a protein fragment of Trypanosoma cruzi heat-shock protein-70when stimulated with a protein fragment of Trypanosoma cruzi heat-shock protein-70

Q2Q1Artículo original255-260We analyzed the effect of the truncated heat-shock protein 70 from Trypanosoma cruzi on maturation of human dendritic cells (DCs) derived from monocytes of peripheral blood mononuclear cells from healthy donors and chagasic patients. The results show that the T-HSP70 is capable of maturing human DCs inducing an increase in the expression level of the CD83, CD86 and human leukocyte antigen-DR surface markers, as well as in the secretion of interleukin (IL)-12, tumor necrosis factor-alpha (TNF-alpha) and IL-6 cytokines. Results also show the existence of a differential functional activity of matured DCs from chagasic patients vs healthy donors in response to T-HSP70 protein and to HSP-70-derived A72 peptide, as only T-HSP70-matured DCs from chagasic patients have an enhanced secretion of IL-10 and a reduced secretion of IL-12. Moreover, the addition of A72 peptide to immature DCs from chagasic patients induced an increase in the percentage of cells expressing CD83 and CD86 molecules regarding to the expression level observed by cells from healthy donors. These findings suggest that T. cruzi HSP70 protein may induce a specific maturation profile on chagasic patients' DCs, which would favor the persistence of the parasite in the human host

Modalidad auxiliar de investigación

Trabajo de grado realizado en modalidad auxiliar de investigación, para optar por el título Doctorado en Cirugía Dental, en el año 2021. Se realizó en el marco del proyecto del Centro de Investigaciones de la Facultad de Odontología Universidad de El Salvador: "Vigilancia epidemiológica de enfermedades bucales en la población atendida en UCSF y atención brindada por odontólogos en servicio social durante la pandemia de covid-19 en el año 2021