Systemic sclerosis at the crossroad of polyautoimmunity

Objectives

Several epidemiological studies have revealed the co-occurrence of other autoimmune diseases (AIDs) within patients with systemic sclerosis (SSc). However, some of these studies were based on small cohorts and wide ranges of prevalence have been reported. Therefore to overcome these limitations of individual studies, we sought to perform a meta-analysis to determine the accurate prevalence of polyautoimmunity in SSc.

Methods

We performed a systematic review and a meta-analysis of literature in MEDLINE and Embase databases from January 1960 to March 2013. All cohort studies reporting on prevalence of other AIDs known to be associated with SSc were analyzed. Prevalence of polyautoimmunity and of each AID were then calculated.

Results

Ten studies reporting polyautoimmunity were identified corresponding to a total of 6102 SSc patients. Overall 1432 patients with at least one AID were identified corresponding to a weighted prevalence of polyautoimmunity equal to 25.7% CI 95% [20.1%–31.6%]. Overall 208/5139 SSc-patients had at least two additional AIDs resulting in a weighted prevalence of 3.9% [3.3%–4.4%]. The most prevalent associated AIDs were autoimmune thyroid disease (10.4%) followed by Sjögren's syndrome (7.7%) and dermatopolymyositis/polymyositis (5.6%).

Conclusion

Our results confirm that SSc polyautoimmunity is a frequent condition in SSc affecting a quarter of SSc-patients. The impact on the phenotype and also on the management and therapy will need to be addressed now in further works.     

Experimental models of dermal fibrosis and systemic sclerosis

Vasculopathy, immunological abnormalities, and fibrosis are the key features in the pathogenesis of systemic sclerosis (SSc). Expression of each of the three pathologic features varies among SSc patients leading to disease heterogeneity and variable organ manifestations. Although the etiology of SSc has not yet been fully elucidated, a growing body of evidence suggests that extracellular matrix overproduction by activated fibroblasts results from a complex interplay between endothelial cells, immune cells and fibroblasts through cell–cell and cell–matrix interactions and communications. Relevant animal models are essential tools to in-depth investigate pathogenesis of SSc. Several murine and avian models are available; however, some models display inflammation followed by fibrosis, whether some others primarily mimic autonomous fibroblast activation. In addition, typical microvascular changes of SSc are only observed in few models. Therefore, none of these animal models encompasses all features of the human disease and a critical selection is mandatory for successful in vivo studies. Hence, we will provide an overview of the most important experimental models of dermal fibrosis and SSc and discuss their respective contribution to the better understanding of SSc pathogenesis.     

Gender difference in ethical abilities of dental students

Walker's comprehensive review of claims of gender difference and gender bias in moral cognition concluded 1) that gender explains a negligible amount of the variability in moral reasoning development, 2) that accumulated evidence does not support claims of gender polarity in moral orientations (i.e., an ethic of care and an ethic of justice), and 3) that future research should focus on the range of psychological processes that engender moral maturity. This study examined whether male and female predoctoral dental students who completed an ethics curriculum grounded in Rest's comprehensive model of moral functioning differed on measures of four capacities: moral sensitivity, moral reasoning, moral motivation, and moral implementation. From archival data at the University of Minnesota School of Dentistry, data on sixty females and sixty males were randomly selected from five cohorts (n=386) who completed an ethics curriculum and outcome measures of the four capacities between 1996 and 2000. Gender differences were not apparent for a measure of moral sensitivity, but were evident for one of the moral reasoning indices, for the responsibility dimension of moral motivation, and for the measure of moral implementation. Implications are drawn for future research and for professional ethics education.     

Intraoperative Near-infrared Imaging for Parathyroid Gland Identification by Auto-fluorescence: A Feasibility Study

Background

Parathyroid glands (PGs) can be particularly hard to distinguish from surrounding tissue and thus can be damaged or removed during thyroidectomy. Postoperative hypoparathyroidism is the most common complication after thyroidectomy. Very recently, it has been found that the parathyroid tissue shows near-infrared (NIR) auto-fluorescence which could be used for intraoperative detection, without any use of contrast agents. The work described here presents a histological validation ex vivo of the NIR imaging procedure and evaluates intraoperative PG detection by NIR auto-fluorescence using for the first time to our knowledge a commercially available clinical NIR imaging device.

Methods

Ex vivo study on resected operative specimens combined with a prospective in vivo study of consecutive patients who underwent total or partial thyroid, or parathyroid surgery at a comprehensive cancer center. During surgery, any tissue suspected to be a potential PG by the surgeon was imaged with the Fluobeam 800 ^® system. NIR imaging was compared to conventional histology (ex vivo) and/or visual identification by the surgeon (in vivo).

Results

We have validated NIR auto-fluorescence with an ex vivo study including 28 specimens. Sensitivity and specificity were 94.1 and 80 %, respectively. Intraoperative NIR imaging was performed in 35 patients and 81 parathyroids were identified. In 80/81 cases, the fluorescence signal was subjectively obvious on real-time visualization. We determined that PG fluorescence is 2.93 ± 1.59 times greater than thyroid fluorescence in vivo.

Conclusions

Real-time NIR imaging based on parathyroid auto-fluorescence is fast, safe, and non-invasive and shows very encouraging results, for intraoperative parathyroid identification.

     

Nutritional Status Prior to Laparoscopic Sleeve Gastrectomy Surgery

Background

Two main causes for nutrient deficiencies following bariatric surgery (BS) are pre-operative deficiencies and favoring foods with high-energy density and poor micronutrient content. The aims of this study were to evaluate nutritional status and gender differences and the prevalence of nutritional deficiencies among candidates for laparoscopic sleeve gastrectomy (LSG) surgery.

Methods

A cross-sectional analysis of pre-surgery data collected as part of a randomized clinical trial on 100 morbidly obese patients with non-alcoholic fatty liver disease (NAFLD) admitted to LSG surgery at Assuta Medical Center between February 2014 and January 2015. Anthropometrics, food intake, and fasting blood tests were evaluated during the baseline visit.

Results

One-hundred patients completed the pre-operative measurements (60 % female) with a mean age of 41.9?±?9.8 years and a mean BMI of 42.3?±?4.7 kg/m². Pre-operatively, deficiencies for iron, ferritin, folic acid, vitamin B1, vitamin B12, vitamin D, and hemoglobin were 6, 1, 1, 6, 0, 22, and 6 %, respectively. Pre-surgery, mean energy, protein, fat, and carbohydrate intake were 2710.7?±?1275.7 kcal/day, 114.2?±?48.5, 110.6?±?54.5, and 321.6?±?176.1 gr/day, respectively. The intakes for iron, calcium, folic acid, vitamin B12, and vitamin B1 were below the Dietary Reference Intake (DRI) recommendations for 46, 48, 58, 14, and 34 % of the study population, respectively.

Conclusion

We found a low prevalence of nutritional deficiencies pre-operatively except for vitamin D. Most micronutrient intake did not reach the DRI recommendations, despite high-caloric and macronutrient intake indicating a poor dietary quality.

     

Differential capacity of T cell priming in naive donors of promiscuous CD4+ T cell epitopes of HCV NS3 and Core proteins

To understand the inter-individual and virus-independent variability of CD4+ T cell responses to HCV components, we evaluated the effect on these responses of HLA II molecules in uninfected healthy donors. Using HLA II-specific binding assays, we identified, in the Core and NS3 proteins, 21 long fragments and 24 15-mer peptides that bound to four to eight of the most preponderant HLA II molecules. We then evaluated the priming capacity of eight long promiscuous peptides in 12 HLA-unrelated healthy donors. The NS3 1250-1264 peptide primed T cells in all the naive donors, while five others were stimulating in at least half of the individuals. We also report sequences that bind to multiple HLA II molecules but are weakly immunogenic. We therefore conclude that (i) broad HLA II specificity is only a prerequisite for a peptide to be stimulating in multiple individuals, and (ii) promiscuous peptides widely differ in their capacity to prime CD4+ T cells from uninfected healthy donors. We suggest that these priming differences result from inter-individual variations in the peptide-specific T cell repertoire. Interestingly, five of the most immunogenic peptides we identified correspond to frequently targeted T cell epitopes in infected patients.