👤 Gabriela M Repetto

A small fraction of the proteins present in human plasma can be found as circulating protein aggregates. Such aggregates are formed by prone to aggregation proteins and different stimuli promote the aggregation process. Fe(III) is a redox active metal ion which also actively interacts with proteins. The aim of this work is to identify the prone to aggregation plasma proteins in presence of Fe(III) in order to outline potential targets of these circulating protein aggregates. Here we show that Fe(III) induces the formation of protein aggregates from human plasma proteins. A concentration of 100 μM Fe(III) aggregates roughly 5 % of the total plasma protein assayed. When assayed by SDS-PAGE/silver-staining, a rather homogeneous aggregate can be observed with one major protein with a molecular weight matching that of immunoglobulin G (IgG) (150k Da). Additionally, the band corresponding to albumin (66 kDa) which is the main plasma protein was absent. The identity of IgG within the aggregate and albumin depletion was corroborated by liquid chromatography-mass spectrometry. Additionally, some other proteins could be identified within the aggregate such as fibrinogen, fibronectin and Apo-B. Then, the identity of the IgG and depletion of albumin was corroborated by Western blot. It should be noted that aggregated IgGs are strong activators of inflammatory pathways involving neutrophil oxidative burst, complement cascade activation and platelet release of active amines. Therefore, the existence of a potential link between the formation of Fe(III)-induced protein aggregates and inflammation should be further explored. Show less

The treatment of paediatric Hodgkin lymphoma (HL) has steadily improved over the years, so that 10- years survival exceed 80%. The purpose of this study was to identify prognostic markers for relapsed HL that might contribute to optimize therapeutic approaches. To this aim we retrospectively analysed differential protein expression profiles obtained from plasma of children/adolescents with HL (age ranging from 10 to 18 years) collected at diagnosis. We examined the protein profiles of 15 HL relapsed (R) patients compared with 14 HL not relapsed (NR) patients treated with the same LH-2004 protocol. Two dimensional difference in gel electrophoresis (2D-DIGE) revealed significant differences (fold change > 1.5; Student's T-test Show less

22q11.2 microdeletion syndrome (22q11.2DS) is the most common microdeletion disorder in humans, with an incidence of 1/4000 live births. It is caused by a heterozygous deletion of 1.5-3 Mb on chromosome region 22q11.2. Patients with the deletion present features that include neuropsychiatric problems, craniofacial abnormalities and cardiovascular malformations. However, the phenotype is highly variable and the factors related to the clinical heterogeneity are not fully understood. About 65% of patients with 22q11.2DS have congenital heart defects (CHD). The main goal of this study was to identify common CNVs in 22q11.2DS patients that could be associated with the incomplete penetrance of CHD. Analysis of genomic DNA from 253 patients with 22q11.2DS using array technology showed an association between a microduplication located in region 17q21.31 and CHD (p-value = 0.023, OR = 2.75, 95% CI = 1.17-7.03). This region includes the first three exons of KANSL1 gene. Bioinformatic analysis showed that KANSL1 and CRKL, a gene in the commonly deleted region of 22q11.2DS, are part of the same regulatory module in a miRNA-mRNA network. These results show that a KANSL1 microduplication, in combination with the 22q11.2 deletion, is associated with increased risk of CHD in these patients, suggesting that KANSL1 plays a role as a modifier gene in 22q11.2DS patients. Show less