The role of the gastrointestinal tract in the pathogenesis of rheumatic diseases

Dysregulation of the intestinal epithelial barrier in genetically susceptible individuals may lead to both intestinal and extraintestinal autoimmune disorders. There is emerging literature on the role of microbiota changes in the pathogenesis of systemic rheumatic diseases such as rheumatoid arthritis, spondyloarthropathies, and connective tissue diseases. Although the role of the gastrointestinal tract in the pathogenesis of spondyloartropathies is well defined and many studies underline the importance of gastrointestinal inflammation in modulating local and systemic inflammation, the data are inconclusive regarding the effect of dysbiosis on rheumatoid arthritis and connective tissue diseases. This review aims to summarize current data on the role of the gastrointestinal involvement and intestinal microbiota in the pathogenesis of systemic rheumatic disease

Breastfeeding education: where are we going? A systematic review article

Background: UNICEF (United Nations International Children’s Emergency Fund) and WHO estimate that if all babies were breastfed for at least the first six months of their lives, the rate of morbidity and malnutrition would sig-nificantly decrease all over the world. In this view, these two organizations promoted a worldwide campaign for breastfeeding, creating the Baby Friendly Hospital Initiative (BFHI) that encourages good practices for the promotion of breastfeeding in hospitals. The aim of our study was to review the available evidence regarding the positive effects of breastfeeding, in order to suggest to most appropriate strategy to support it. Methods: The main databases including Scopus, PubMed, MEDLINE, Google scholar and Science Direct were researched to obtain the original papers related to breastfeeding education. The main terms used to literature search were "Breastfeeding education", Breastfeeding support", and “Breastfeeding healthcare policy”. The timeframe in-cluded the obtained articles was from 1980 to 2015. Results: Our analysis confirms that healthcare providers play a pivotal role in education and encouraging mothers to begin and continue breastfeeding. In this view, the adequate training of healthcare providers seems to be mandatory in order to support this practice. Moreover, adequate facilities are needed in order to promote and support breastfeeding. Conclusion: Considering the available evidence, breastfeeding should be supported among all the mothers. Based on the positive data emerging from the public awareness campaign in different Countries of the world, we strongly en-courage an accurate training for doctors and midwives and the implementation of adequate facilities in order to sup-port breastfeeding

Are Toll-Like Receptors and Decoy Receptors Involved in the Immunopathogenesis of Systemic Lupus Erythematosus and Lupus-Like Syndromes?

In this paper we focus our attention on the role of two families of receptors, Toll-like receptors (TLR) and decoy receptors (DcR) involved in the generation of systemic lupus erythematosus (SLE) and lupus-like syndromes in human and mouse models. To date, these molecules were described in several autoimmune disorders such as rheumatoid arthritis, antiphospholipids syndrome, bowel inflammation, and SLE. Here, we summarize the findings of recent investigations on TLR and DcR and their role in the immunopathogenesis of the SLE

A Th1 but not a Th17 response is present in the gastrointestinal involvement of Behçet's disease

OBJECTIVES: Behçet's disease has been historically classified as a Th1 disease. The recently described IL-17/IL-23 pathway seems to play an important role in many inflammatory diseases and in the intestinal abnormalities of AS and CD. The aim of the present study was to evaluate the IL-17/IL-23 axis in parallel with Th1 and IL-27 response in the intestine of patients with BD and gastrointestinal abnormalities. METHODS: Quantitative TaqMan reverse transcriptase-polymerase chain reaction (RT-PCR) was utilised for all determinations on ileal biopsy specimens obtained from BD, AS and CD patients. The serum levels of Th1 and Th17 cytokines were evaluated by enzyme-linked immunosorbent assay. RESULTS: A Th1 but not a Th17 response is present in the gastrointestinal involvement of Behçet's disease. CONCLUSIONS: Although BD shares clinical manifestations with both CD and AS, the immunologic abnormalities seen in the intestine are quite different, indicating that other immune mechanisms should be taken into account

Dysbiosis and zonulin upregulation alter gut epithelial and vascular barriers in patients with ankylosing spondylitis

Background: Dysbiosis has been recently demonstrated in patients with ankylosing spondylitis (AS) but its implications in the modulation of intestinal immune responses have never been studied. The aim of this study was to investigate the role of ileal bacteria in modulating local and systemic immune responses in AS. Methods: Ileal biopsies were obtained from 50 HLA-B27+ patients with AS and 20 normal subjects. Silver stain was used to visualise bacteria. Ileal expression of tight and adherens junction proteins was investigated by TaqMan real-time (RT)-PCR and immunohistochemistry. Serum levels of lipopolysaccharide (LPS), LPS-binding protein (LPS-BP), intestinal fatty acid-BP (iFABP) and zonulin were assayed by ELISA. Monocyte immunological functions were studied in in vitro experiments. In addition the effects of antibiotics on tight junctions in human leukocyte antigen (HLA)-B27 transgenic (TG) rats were assessed. Results: Adherent and invasive bacteria were observed in the gut of patients with AS with the bacterial scores significantly correlated with gut inflammation. Impairment of the gut vascular barrier (GVB) was also present in AS, accompanied by significant upregulation of zonulin, and associated with high serum levels of LPS, LPS-BP, iFABP and zonulin. In in vitro studies zonulin altered endothelial tight junctions while its epithelial release was modulated by isolated AS ileal bacteria. AS circulating monocytes displayed an anergic phenotype partially restored by ex vivo stimulation with LPS+sCD14 and their stimulation with recombinant zonulin induced a clear M2 phenotype. Antibiotics restored tight junction function in HLA-B27 TG rats. Conclusions: Bacterial ileitis, increased zonulin expression and damaged intestinal mucosal barrier and GVB, characterises the gut of patients with AS and are associated with increased blood levels of zonulin, and bacterial products. Bacterial products and zonulin influence monocyte behaviour

The analysis of SUDEP forensic autopsies leading to preventable events

Introduction: The diagnosis of unexpected death by excluding non-natural causes, particularly in subjects with epilepsy, is a topic of interest and it is difficult to identify in the forensic field. Health professionals sometimes are faced with cases of sudden death, generally in young adults with a long history of epilepsy that require, for judicial purposes, an explanation in terms of cause and means to determine the death. SUDEP is an entity diagnosed by the exclusion of other causes that may have led to death, and then for forensic purposes, it requires particular attention and knowledge, and there is difficulty in identifying it. Our contribution aims to illustrate the scientific community pathological findings, medical history, and circumstantial evidence of four cases of sudden death in epileptic subjects. Method: We illustrated four cases of judicial autopsies from the Institute of Forensic Medicine of Palermo, Italy; the purpose was to exclude the criminal intervention in determining the death as non-natural. The study of victims’ medical history, the toxicological investigations, and the autopsy findings analyzed both from macroscopic and microscopic aspects have made it possible to highlight some findings that can be traced back to SUDEP despite the small sample of subjects studied. Results: These presented findings of four SUDEP cases could help forensic pathologists in recognizing this entity, by highlighting its characteristics, and allowing for a pathological classification, also in relation to the use of drugs for epilepsy treatment and circumstances of death. Discussion: To obtain a definite diagnosis of SUDEP, a complex investigation process is required in a multidisciplinary approach. Considering the literature review with criticism, it could allow health professionals to select the characteristics of epileptic patients at risk of sudden death. Processing human behaviors, molecular and histopathological findings of the autopsies, but also the physiological, and pathological human body system functions thanks to Artificial Intelligence, could be the key to explaining SUDEP mechanisms and the future results to prevent it

Mesenchymal stromal cells and rheumatic diseases: new tools from pathogenesis to regenerative therapies

In recent years, mesenchymal stromal cells (MSCs) have been largely investigated and tested as a new therapeutic tool for several clinical applications, including the treatment of different rheumatic diseases. MSCs are responsible for the normal turnover and maintenance of adult mesenchymal tissues as the result of their multipotent differentiation abilities and their secretion of a variety of cytokines and growth factors. Although initially derived from bone marrow, MSCs are present in many different tissues such as many peri-articular tissues. MSCs may exert immune-modulatory properties, modulating different immune cells in both in vitro and in vivo models, and they are considered immune-privileged cells. At present, these capacities are considered the most intriguing aspect of their biology, introducing the possibility that these cells may be used as effective therapy in autoimmune diseases. Therefore, stem cell therapies may represent an innovative approach for the treatment of rheumatic diseases, especially for the forms that are not responsive to standard treatments or alternatively still lacking a definite therapy. At present, although the data from scientific literature appear to suggest that such treatments might be more effective whether administered as soon as possible, the use of MSCs in clinical practice is likely to be restricted to patients with a long history of a severe refractory disease. Further results from larger clinical trials are needed to corroborate preclinical findings and human non-controlled studies, and advancement in the knowledge of MSCs might provide information about the therapeutic role of these cells in the treatment of many rheumatic diseases