Inmunologia (Barcelona, Spain : 1987)最新文献

Previously a refinement of a methodology was developed based on set theory and probability, with the aim of improving the predictive ability of CD4 T cells (LT-CD4) for HIV/AIDS from the total number of leukocytes and lymphocytes. In this work the clinical applicability of the method was shown by refining prediction in 150 samples. Taking data of leukocytes/mm³, lymphocytes/mm³, and LT-CD4 cells/mm³ of each patient, called triples, they were organized from highest to lowest based on the number of leukocytes, to evaluate ranges of 1,000 leukocytes. The membership of the triples to the set A∪C, B∪D was established, as well as the intersection between the two sets (A∪B)∩(B∪D), in which a prediction of the number of CD4 associated with specific values of leukocytes and lymphocytes is established. The number of elements belonging to each set was counted and the probability of belonging to each of the ranges tested was determined. A total of 7 out of the 9 ranges of leukocytes measured showed a probability of success equal to or greater than 0,76, achieving a probability of 1 in the ranks lower than 4.000/mm³ and 3.000/mm³, respectively. The ability of the methodology for determining the value of the LT-CD4 was demonstrated, achieving a higher predictive capacity than the unrefined methodology. The evidence shows that the applied methodology is effective for clinical use, thus leading to a reduction of costs and resources.

Psoriasis is a chronic inflammatory disease of the skin, of autoimmune origin, with different cells implicated in the aetiopathology, such as T helper lymphocytes (Th1 and Th17), keratinocytes, and cytokines produced by these cells. The epigenetic regulatory mechanisms are the junction between environmental exposure and genetic factors. It is known that microRNAs (miRNAs), single chain RNAs, are actively involved in epigenetic regulation. Alterations in the miR-125b, miR-424, miR- 21 and miR-203 expression, and others, have been involved in different aspects of the disease. Global studies of miRNA expression performed using microarrays and by direct RNA sequencing revealed important differences in miRNA expression in normal skin and psoriatic individuals. These miRNAs can be considered as potential therapeutic targets or biomarkers of disease.

We review the neuronal antibodies described in CNS disorders in order to clarify their diagnostic value. In this work, the neuronal antibodies associated with syndromes resulting from CNS neuronal dysfunction were classified into two groups according to the location of the antigen inside the neuron or in the cell membrane. Group I includes antibodies that target intracellular antigens and are probably not pathogenic. They include onconeural antibodies (Hu [ANNA1], Yo [PCA1], Ri [ANNA2], CV2 [CRMP5], amphiphysin, Ma2, Tr, SOX1), which are useful for the diagnosis of paraneoplastic neurological syndromes (PNS). Other antibodies of this group, mainly anti-glutamic acid decarboxylase (GAD) antibodies, identify non-paraneoplastic syndromes (PNS), such as stiff-person syndrome (SPS), cerebellar ataxia, and limbic encephalitis (LE). Group II antibodies recognize neuronal surface antigens. Antibodies in this group are associated with characteristic CNS syndromes, but their detection does not indicate that the disorder is paraneoplastic. The most frequent are the anti-receptor NMDA antibodies, followed by the antibodies against the protein LGI1 associated with the potassium channel. Other less common antibodies include those against the receptors of AMPA, GABAb, mGluR 1 and 5, and against CASPR2. A pathogenic role of the antibodies is suggested by the response of symptoms to immunotherapy, and the correlation between antibody titers and neurological outcome.

Rheumatoid arthritis is an autoimmune disease characterized by polyarticular inflammation, swelling and inflammation that affects more than 1% of the world population. The pathobiology of rheumatoid arthritis involves several cell populations as T lymphocytes, B, macrófagosy fibroblasts, and a complex proinflammatory cytokines interactions. Conventional and biologic therapies do not always work or produce only a partial improvement. Immunological tolerance is a mechanism by which the immune system prevents autoreactivity. The aim of this pilot study was to evaluate the efficacy of peptides from an from articular cartilage hydrolysate extracted of tarsus (HCA) for the treatment of rheumatoid arthritis in a model of rheumatoid arthritis (AAE) in rabbits. AAE animals showed inflammation and pain within de first month of the primary immunization that was reversed in the AAE + HCA group. The control group showed a normal unnaffected synovial tissue. The AAE group revealed an inflamatory process whith synovial hyperplasia, filtering in lymphocytes and vascular proliferation. The treated group decreased significantly inflammation, lymphocyte proliferation and angiogenesis. Arthritic rabbits increased the levels in flammatory markers as nitric oxide, interferon gamma (INF-ɣ) and tumor necrosis factor alpha (TNF-α) compared to control and significantly reduced levels of interleukin 4 (IL-4). The treatment showed a significant reduction of nitricoxide, IFN-gamma and TNF-alpha and an increase in IL-4. This work suggests that this therapy may be useful in the clinical aspect and the biochemical and immune parameters. Future studies with larger numbers of animals and other laboratory parameters may provide additional evidence in this regard.

Objective

This study was designed to examine the effects of hepatocyte growth factor (HGF) gene delivery on vascular inflammation and hypertension in spontaneously hypertensive rats (SHR). We speculated that HGF deficiency could play a key role in the pathogenesis of hypertension in SHR, and that increasing HGF levels will produce prolonged decreases in blood pressure due to reduced vascular inflammation.

Materials and methods

Fifteen-week old male SHRs received weekly hydrodynamic injections of a naked plasmid containing human HGF (pCMV-HGF) (1 mg/kg) or empty vector (pcDNA3.1) for 6 weeks. Two groups of Wistar-Kyoto (WKY) rats were used as controls (n = 6) and treated in the same manner. The activation of NF-κB was assessed by Western blot and mRNA expression of pro-inflammatory cytokines by real-time PCR and Western blot.

Results

Blood pressure, NF-κB activation and expression of IL-6, MCP-1 and RANTES were significantly higher in SHR than in the control WKY. The HGF gene therapy normalized NF-κB activity, pro-inflammatory cytokines expression, and decreased the hypertension in SHR.

Conclusion

These observations suggest that decreased aorta HGF concentration may have a role in the vascular inflammation observed in SHR, and demonstrate that increasing HGF is a potential therapeutic target in the treatment of hypertension.

More is now known of the involvement of HLA-DP region in the pathogenesis of the leukemias through several previousstudies showing interference of these molecules in modulating the immune response to pathogens. For evaluation of HLA alleles and haplotypes DPA1*/DPB1* (28 alleles HLA DPA1* and 123 of HLA- DPB1*) Olerup SSP ™PCR (Genovision) was used in 48 patients with ALL, 48 CML, and 48 Venezuelan twins as controls. For HLA/leukemias, a relative risk (RR) > 3 was considered to be a positive association and negative with an RR < 3, with a p corrected P<.05. ALL patients confirmed positive associations with DPA1*0105 allele, and negative with DPA1*010301-010302. In addition, they were positively associated with DPA1*0106 and *0107, with DPA1*020101-020106 being negatively associated with ALL. DPA1*0105, *0108 and *0109 were negatively associated with CML. The observed frequencies of HLA-DPB1* 01:01, 02:01, 03:01, 04:01 and 4:02 alleles in Venezuelan, which twins were between 7 and 16%, were higher than those of leukemic patients. Negative associations of DPB1*2:01, *3:01 and LLA were confined. No positive associations were observed with ALL. Non-confirmed positive associations were observed between DPB1*99:01 and CML. Haplotypes HLA-DPA1*01:03-DPB1*4:01, *2:01, *99:01 were strongly positively associated with CML. DPA1*1:09-DPB1*2:01, *4:01 were negatively associated with the CML. DPA1*1:03-DPB1*4:02; DPA1*01:09-DPB1*2:01, *4:01 and DPA1*02:01-DPB1*04:02 were negatively associated with ALL. The DPB1* single region does not appear to be associated with leukemia in the Venezuelan population. The strong association with several haplotypes DPA*1/DPB1* and LMC suggests massive differences between the pathogenesis of both diseases.

Introduction

Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by defects in the respiratory burst of phagocytes. Affected patients often suffer from granulomas and recurrent infections, mainly due to encapsulated bacteria.

Aim

To standardize the dihydrorhodamine test (DHR) in Colombia used for the diagnosis of CGD by evaluating the respiratory burst in human blood neutrophils and monocytes after in vitro activation.

Methods

Phagocyte respiratory burst in peripheral blood samples from 10 healthy controls was evaluated by flow cytometry after leukocyte activation with several concentrations of phorbol myristate acetate (PMA). The different oxidation patterns of DHR in X-linked or autosomal recessive CGD were also obtained.

Results

The most suitable concentrations of PMA for the evaluation of the respiratory burst in peripheral blood were 0.2 to 5 μg/ml. Reference values for this test in neutrophils from our population were established. It was shown that the oxidation patterns of DHR in monocytes were not always identical to those observed in neutrophils.

Conclusion

The evaluation of DHR oxidation by flow cytometry is a screening method that easily identifies the different phenotypes of CGD, with good sensitivity and at a lower cost. However, it is crucial that every laboratory establishes its own normal range for this test, in order to achieve the accurate characterization of this condition. DHR oxidation patterns may be also evaluated in different blood cells, since cell type-specific defects have also been reported.