Inmunologia (Barcelona, Spain : 1987)最新文献

There is evidence that supports the hypothesis of the existence of cancer stem cells (CSC), in which it postulates that these are responsible for the initiation, recurrence, metástasis, and resistance to cancer treatments, thus creating a need for therapies that specifically target these subpopulations of cells with stem cell characteristics in most malignant tumors with mixed cell phenotypes. Since its advent, immunotherapy has been used as an attractive approach due to the many shortcomings of conventional surgery, radiotherapy and chemotherapy in the treatment of cancer. Within tumor subsets neoplastically transformed cells demonstrate surface expression of molecules that are not typically present on the surface of the surrounding normal cells. In some cases, especially in malignant melanoma, the cytotoxic T lymphocytes (CTL) directed against tumor associated antigens (TAA) have been isolated to raise antibodies and somehow reduce the disease. The focus of cancer vaccine therapy is based on the idea that the immune system could mount a rejection response force against conglomerate neoplastically transformed cells. However, due to the low immunogenicity of TAA, down-regulation of MHC molecules, the lack of expression of appropriate co-stimulatory molecule, cytokine secretion inmunoinhibitorias etc., they rarely met expectations. This is why new markers that are not only safe and allow immunotherapy directed against CSC are now being sought, but also tumor eradication could be achieved with the combination of many therapies in order to have an efficient outcome in the treatment of this disease currently affecting the world.

Background

Changes in various cytokine activities have been reported during both HBV and HCV infections, while an imbalance of pro-inflammatory and anti-inflammatory cytokine production influences their immunopathogenesis. The aims of the present study are (a) to measure serum levels of interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), interleukin-10 (IL-10), interleukin-2 (IL-2) and interleukin-4 (IL-4) in a sample of patients affected either by chronic HBV infection or by chronic HCV infection and in healthy controls (b) to correlate serum levels of IL-6, TNF-α, IL-10, IL-2 and IL-4 with biochemical markers of liver disease and (c) to evaluate differences of the aforementioned cytokines between HBV and HCV patients, as well as between patients and healthy controls.

Methods

The study population consisted of 50 patients with chronic hepatitis B, 40 patients with chronic hepatitis C and 30 healthy controls aged between 28 and 75 years. Biochemical markers of liver disease were evaluated by routine methods approved by IFCC. Serum concentrations of IL-6, TNF-α, IL-10, IL-2 and IL-4 were determined with the Human Cytokine/Chemokine Panel I Merck Millipore.

Results

HBV patients showed statistically significant difference in TNF-α and IL-2 levels, versus healthy controls. HCV patients showed statistically significant difference in TNF-α, IL-10 and IL-2 levels versus healthy controls. IL10 and IL-2 levels were significantly different between HBV and HCV patients.

Conclusions

This study evaluated the serum cytokine levels (IL-6, TNF-α, IL-10, IL-2 and IL-4) of chronic hepatitis B or C patients, as well as the differences in such levels between patients and healthy controls. Correlations of cytokine levels with biochemical markers of liver disease were also observed, reflecting the degree of activity of the inflammatory process in the liver.

Invariant natural killer (iNK) T lymphocytes (iNKTL) were initially identified due to having similar characteristics to NK and T cells. Nowadays, it is known that these cells are T lymphocytes with unique characteristics, from their maturing process and differentiation in the thymus to the response at specific stimuli. Studies in mice have been useful for examining the maturing process and differentiation pathways of iNKTL. In these pathways the CD1d molecule has a fundamental role in the selection of their precursors, and also in the peripheral glycolipid presentation for the activation of iNKTL. Four sub-populations of iNKTL CD4⁺, CD8αβ⁺, CD8αα⁺ and Double Negatives, were identified in human peripheral blood. They particularly cooperate and interact with others immune cells. The information obtained by studying iNKTL opens the possibility of proposing this cell line as a therapeutic alternative, but further studies on the behavior of this type of lymphocyte are needed.

Objective

The assessment of prognostic biomarkers in monoclonal gammopathies of uncertain significance (MGUS) requires using large cohorts and long follow-ups, due to the low rate of conversion to multiple myeloma (MM). The aim of this article is to develop a model that allows smaller cohorts and shorter follow-ups to be used with high reliability.

Patients and methods

A total of 64 MGUS patients were studied and followed-up prospectively for 6 ± 0.24 years. Patients were classified as evolving or non-evolving, depending on whether the monoclonal protein levels increased or not over time. The risk of conversion to MM was tested based on these phenotypes, and whether the factors that predict conversion to MM are also associated with the appearance of an evolving phenotype.

Results

Eleven patients showed an evolving phenotype, and 53 a non-evolving one. All patients who converted to MM previously showed evolving phenotype (P = .003). At diagnosis, evolving phenotype associated with monoclonal gammopathies of IgA isotype (27 vs. 9%), monoclonal IgG levels above 1,500 mg/dl (P = .007, OR 9.8) and altered kappa/lambda ratios (P = .001, OR 11.7).

Conclusions

Risk factors for developing an evolving phenotype in MGUS patients are the same as those already described for the development of MM. These data show the validity of the evolving/non-evolving model to study markers to predict the outcome of MGUS patients, and confirm the role of the levels of monoclonal IgG and the light chains ratio in the prognosis of this disease.