The majority of human autoimmune diseases are characterized by female predominance. Although sex hormone influences have been suggested to explain this phenomenon, the mechanism remains unclear. In contrast to the role of hormones, it has been suggested, based on pilot data in primary biliary cirrhosis, that there is an elevation of monosomy X in autoimmune disease. Using peripheral white blood cells from women with systemic sclerosis (SSc), autoimmune thyroid disease (AITD), or healthy age-matched control women, we studied the presence of monosomy X rates using fluorescence in situ hybridization. We also performed dual-color fluorescence in situ hybridization analysis with a chromosome Y α-satellite probe to determine the presence of the Y chromosome in the monosomic cells. In subsets of patients and controls, we determined X monosomy rates in white blood cell subpopulations. The rates of monosomy X increased with age in all three populations. However, the rate of monosomy X was significantly higher in patients with SSc and AITD when compared with healthy women (6.2 ± 0.3% and 4.3 ± 0.3%, respectively, vs 2.9 ± 0.2% in healthy women, p < 0.0001 in both comparisons). Importantly, X monosomy rate was more frequent in peripheral T and B lymphocytes than in the other blood cell populations, and there was no evidence for the presence of male fetal microchimerism. These data highlight the thesis that chromosome instability is common to women with SSc and AITD and that haploinsufficiency for X-linked genes may be a critical factor for the female predominance of autoimmune diseases.

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Objective. Levels of interleukin-17A (IL-17A) have been found to be increased in synovial fluid from individuals with systemic sclerosis (SSc). This study was undertaken to investigate whether IL-17A-producing cells are present in affected SSc skin, and whether IL-17A exerts a role in the transdifferentiation of myofibroblasts.Methods. Skin biopsy samples were obtained from the involved skin of 8 SSc patients and from 8 healthy control donors undergoing plastic surgery. Immunohistochemistry and multicolor immunofluorescence techniques were used to identify and quantify the cell subsets in vivo, including IL-17A؉, IL-4؉, CD3؉, tryptase-positive, ␣-smooth muscle actin (␣-SMA)-positive, myeloperoxidase-positive, and CD1a؉ cells. Dermal fibroblast cell lines were generated from all skin biopsy samples, and quantitative polymerase chain reaction, Western blotting, and solid-phase assays were used to quantify ␣-SMA, type I collagen, and matrix metalloproteinase 1 (MMP-1) production by the cultured fibroblasts.Results. IL-17A؉ cells were significantly more numerous in SSc skin than in healthy control skin (P ‫؍‬ 0.0019) and were observed to be present in both the superficial and deep dermis. Involvement of both T cells and tryptase-positive mast cells in the production of IL-17A was observed. Fibroblasts positive for ␣-SMA were found adjacent to IL-17A؉ cells, but not IL-4؉ cells. However, IL-17A did not induce ␣-SMA expression in cultured fibroblasts. In the presence of IL-17A, the ␣-SMA expression induced in response to transforming growth factor ␤ was decreased, while MMP-1 production was directly enhanced. Furthermore, the frequency of IL-17A؉ cells was higher in the skin of SSc patients with greater severity of skin fibrosis (lower global skin thickness score).Conclusion. IL-17A؉ cells belonging to the innate and adaptive immune system are numerous in SSc skin. IL-17A participates in inflammation while exerting an inhibitory activity on myofibroblast transdifferentiation. These findings are consistent with the notion that IL-17A has a direct negative-regulatory role in the development of dermal fibrosis in humans.

Objective. To construct a prognostic index based on nailfold capillaroscopic examinations that is capable of predicting the 5-year transition from isolated Raynaud's phenomenon (RP) to RP secondary to scleroderma spectrum disorders (SSDs).Methods. The study involved 104 consecutive adult patients with a clinical history of isolated RP, and the index was externally validated in another cohort of 100 patients with the same characteristics. Both groups were followed up for 1-8 years. Six variables were examined because of their potential prognostic relevance (branching, enlarged and giant loops, capillary disorganization, microhemorrhages, and the number of capillaries).Results. The only factors that played a significant prognostic role were the presence of giant loops (hazard ratio [HR] 2.64, P ‫؍‬ 0.008) and microhemorrhages (HR 2.33, P ‫؍‬ 0.01), and the number of capillaries (analyzed as a continuous variable). The adjusted prognostic role of these factors was evaluated by means of multivariate regression analysis, and the results were used to construct an algorithm-based prognostic index. The model was internally and externally validated.Conclusion. Our prognostic capillaroscopic index identifies RP patients in whom the risk of developing SSDs is high. This model is a weighted combination of different capillaroscopy parameters that allows physicians to stratify RP patients easily, using a relatively simple diagram to deduce the prognosis. Our results suggest that this index could be used in clinical practice, and its further inclusion in prospective studies will undoubtedly help in exploring its potential in predicting treatment response.Raynaud's phenomenon (RP) is defined as bouts of reversible vasospastic ischemia of the digits that are typically manifested upon exposure to the cold and/or in association with emotional stress. It is characterized by well-demarcated blanching (ischemia), which leads to cyanosis (deoxygenation), followed by postischemic red flushing upon rewarming (reperfusion). A biphasic or triphasic color change may occur. Episodes of RP may be accompanied by varying degrees of paresthesia, numbness, and pain (1,2).Previous population-based studies have shown that RP is a very common problem in clinical practice: its prevalence in the US is ϳ4-9% among women and ϳ3-6% among men (3,4). The prevalence of RP in Europe is 2-21% and is closely related to climatic conditions (5-7).RP may be primary (uncomplicated) when it occurs without an underlying disease or secondary when it develops in the context of an associated disorder.

Although more common in women, SSc appears as strikingly more severe in men. Our results obtained through the largest worldwide database demonstrate a higher risk of severe cardiovascular involvement in men. These results raise the point of including sex in the management and the decision-making process.

Objective. To assess fetal and maternal outcomes in women with systemic sclerosis (SSc). Methods. Prospectively collected data on

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Our data show that joint involvement is a common presenting feature of SSc. In this report, we show that anti-CCP antibodies can be detected also in patients with SSc, but they are generally less commonly present than in adults with rheumatoid arthritis (RA). Thus, the finding of high titers of anti-CCP antibodies may help to define the diagnosis of overlap syndrome SSc/RA and facilitate diagnosis and appropriate treatment.