The Sex Bias in Systemic Sclerosis: on the Possible Mechanisms Underlying the Female Disease Preponderance

Systemic sclerosis is a multifactorial and heterogeneous disease. Genetic and environmental factors are known to interplay in the onset and progression of systemic sclerosis. Sex plays an important and determinant role in the development of such a disorder. Systemic sclerosis shows a significant female preponderance. However, the reason for this female preponderance is incompletely understood. Hormonal status, genetic and epigenetic differences, and lifestyle have been considered in order to explain female preponderance in systemic sclerosis. Sex chromosomes play a determinant role in contributing to systemic sclerosis onset and progression, as well as in its sex-biased prevalence. It is known, in fact, that X chromosome contains many sex- and immuno-related genes, thus contributing to immuno tolerance and sex hormone status. This review focuses mainly on the recent progress on epigenetic mechanisms—exclusively linked to the X chromosome—which would contribute to the development of systemic sclerosis. Furthermore, we report also some hypotheses (dealing with skewed X chromosome inactivation, X gene reactivation, acquired monosomy) that have been proposed in order to justify the female preponderance in autoimmune diseases. However, despite the intensive efforts in elucidating the mechanisms involved in the pathogenesis of systemic sclerosis, many questions remain still unanswered.     

Persistent Colonization of Nine Cystic Fibrosis Patients with an<Emphasis Type="Italic"> Achromobacter</Emphasis> (<Emphasis Type="Italic">Alcaligenes</Emphasis>)<Emphasis Type="Italic"> xylosoxidans</Emphasis> Clone

The present study was conducted to investigate the increasing incidence of Achromobacter (previously Alcaligenes) xylosoxidans isolates being recovered from sputum samples of cystic fibrosis patients at a cystic fibrosis department for adults in Athens, Greece. During the 1-year study period, a total of 34 isolates were detected persistently in 9 of 71 cystic fibrosis patients. The isolates exhibited resistance to multiple antimicrobial agents. Isolates that were recovered repeatedly from each patient exhibited identical macrorestriction profiles with pulsed-field gel electrophoresis, indicating that the same strain persisted in the lungs of these patients. Isolates from five of the patients were genetically related, suggesting a common-source outbreak of Achromobacter xylosoxidans colonization or infection.     

Menkes protein localization in rat parotid acinar cells

The aim was to study the subcellular localization of the Menkes protein (MNK; ATP7A) in the rat parotid acinar cell. MNK protein is a copper transporting P-type ATPase whose absence or dysfunction causes a fatal neurodegenerative disorder, MNK disease. Rat parotid glands were fixed and low-temperature embedded in Lowicryl K4M resin, and ultrathin sections were prepared for immunocytochemical analysis. Immunolocalization of MNK was demonstrated mainly over the trans Golgi network (TGN) area. Immature and mature secretory granules were also labelled, indicating that MNK protein could be involved here in copper secretion from acinar cells into saliva, consistent with a proposed cariostatic role for copper.     

Epidemiology of antibiotic resistance of human nontyphoidal salmonellae in Greece during an 8-year period (1990-1997)

The susceptibility patterns of 1027 nontyphoidal Salmonella strains of human origin, isolated in Greece between 1990 and 1997, were determined by broth microdilution. From 1990 to 1995, the overall incindence of resistance for both Salmonella enteritidis and S. typhimurium increased. From 1996 onwards, a decrease was observed, which was more evident for S. enteritidis. Regarding the other examined serotypes a substantial proportion of resistant isolates was found only for S. Virhow and S. Hadar.     

Evaluation of circulating CD4+CD25+ and liver-infiltrating Foxp3+ cells in HCV-associated liver disease

In hepatitis C virus (HCV)-associated liver disease, the immune system is unable to clear the viral infection. Previous studies have raised the possibility of an involvement of regulatory T cells (Tregs). In this study, we analysed the peripheral blood from 30 patients with HCV-associated chronic liver disease and 20 healthy controls by flow cytometry for the evaluation of the Treg population [CD4?CD25hi forkhead box protein 3 (Foxp3)?], as well as the activated/effector CD4? T cells (CD4?CD25low) and IFN-γ-secreting cells. We also analysed liver biopsies of the patients by immunohistochemical evaluation of Foxp3? cells. Our results showed higher proportions of CD4?CD25low and IFN-γ? cells in the patients than in the controls. By contrast, the proportions of peripheral CD4?CD25hi cells did not significantly differ. The 11 patients displaying Foxp3? cells in the liver infiltrates showed significantly higher proportions of peripheral CD4?CD25low cells. Moreover, we found lower serum transaminase levels in the patients than in the controls, as shown by Foxp3? immunohistochemistry, although these results were only statistically significant as regards alanine transaminase (ALT). In conclusion, these data suggest that the presence of Tregs infiltrating the liver is associated with high levels of activated/effector T cells in the peripheral blood and lower activity of hepatitis. Therefore, liver-infiltrating Tregs may play a role in limiting tissue damage and may thus support an effective immune response against HCV.