IL-21 effects on human IgE production in response to IL-4 or IL-13

In human atopic disease, IgE sensitizes the allergic response, while IgG4 is protective. Because IL-4 and IL-13 trigger switch recombination to both IgE and IgG4, additional agents must regulate the balance between these isotypes to influence susceptibility or tolerance to atopy. In this report, we define in vitro conditions leading to activation or inhibition of human IgE and IgG4 production by IL-21. IL-21 reduced IL-4-driven IgE synthesis by mitogen-stimulated human PBMC. IL-21 inhibition of human IgE production was not a direct effect on B cells, was not seen following B cell activation with IL-13, and was overcome by CD40 ligation. Neither IFN-gamma, IL-10, IL-12, CD40L expression, nor apoptosis was responsible for the inhibitory effect. In contrast, IL-21-stimulated secretion of IgG4 from PBMC. Our findings indicate that IL-21 may influence the production of both human IgE and IgG4, and thus contribute to the regulation of atopic reactions.     

Identification of Adducts Formed in the Reactions of Malonaldehyde–glyoxal and Malonaldehyde–methylglyoxal with Adenosine and Calf Thymus DNA

The reactions of adenosine with malonaldehyde and glyoxal, and with malonaldehyde and methylglyoxal resulted in the formation of one malonaldehyde–glyoxal and one malonaldehyde–methylglyoxal conjugate adduct, respectively. These adducts were isolated and purified by reversed‐phase liquid chromatography, and structurally characterized by UV, ¹H‐ and ¹³C‐NMR spectroscopy, and mass spectrometry. The malonaldehyde–glyoxal adduct was identified as 8‐(diformylmethyl)‐3‐(β‐D ‐ribofuranosyl)imidazo[2,1‐i]purine (M₁Gx‐A), while the malonaldehyde–methylglyoxal one as 8‐(diformylmethyl)‐7‐methyl‐3‐(β‐D ‐ribofuranosyl)imidazo[2,1‐i]purine (M₁MGx‐A). Both adducts were also observed in calf thymus DNA when incubated in the respective aldehydes under physiological pH and temperature. Moreover, in the reaction of methylglyoxal and malonaldehyde with adenosine, an additional adduct was formed. This adduct was found to consist of one unit derived from methylglyoxal and one unit from formaldehyde. The adduct was identified as N⁶‐(2,3‐dihydroxy‐2‐methylpropanoyl)‐9‐(β‐D ‐ribofuranosyl)purine (MGxFA‐A). Formaldehyde was found to originate from the commercial methylglyoxal in which it was present as an impurity.     

Serum heat shock protein 27 levels in patients with hepatocellular carcinoma

Levels of serum heat shock protein 27 (sHsp27) have been studied in numerous cancer types, but their potential relevance in patients with hepatocellular carcinoma (HCC) is undetermined. Our aim was to compare sHsp27 levels in patients with HCC and HCC-free controls. Specifically, we recruited 71 patients with HCC (80 % with early tumour), 80 patients with chronic liver disease (59 with liver cirrhosis and 21 with chronic active hepatitis) and 42 healthy subjects. sHsp27 was measured by immunoenzymatic assay. Results showed that sHsp27 levels were significantly (p < 0.001) higher in patients with HCC than in the other groups, particularly in those with hepatitis C virus (HCV)-related disease. In HCC patients, sHsp27 levels were not associated with prognostic risk factors, such as size/multiplicity of nodules and stage. In logistic regression analysis, performed in patients with liver disease, log-sHsp27 was associated with a significant age-adjusted 2.5-fold increased odds ratio of HCC and with a significant 4.4-fold higher odds ratio of HCC in the subgroup with HCV-related liver disease. In receiver operating characteristic curve analysis, sensitivity and specificity of the best sHsp27 cut-off value (456.5 pg/ml) for differentiating patients with HCC from those with HCC-free chronic liver disease were 70 and 73 %, respectively. In conclusion, sHsp27 levels are enhanced in patients with HCC and may represent a candidate biomarker of HCC.