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ID PMID Title PublicationDate abstract
27994692 Incidental Findings of Intense Radioiodine Uptake in Struma Ovarii and Bilateral Nonlactat 2016 Dec A 52-year-old woman diagnosed with papillary thyroid carcinoma was referred for (131)I therapy following total thyroidectomy. She was given 4,810 MBq (130 mCi) of (131)I following 4 weeks of thyroid hormone withdrawal. A posttherapy scan showed intense, focal activity in the pelvis and intense, diffuse activity on both sides of the chest, which was localized to the right ovary and both breasts on SPECT/CT examination. She had bilateral nipple pain and a history of antidopaminergic drugs as combination medication for her rheumatoid arthritis and prokinetics during radioiodine therapy. On a (123)I whole-body scan 9 months later after stopping the drugs, bilateral breast uptake was not visible; however, right ovarian focal uptake was still visualized. Bilateral salpingo-oophorectomy was performed, and revealed struma ovarii with substantial internal necrosis due to radioiodine therapy. This case is interesting as two rare entities, (131)I therapy-related struma ovarii and drug-related breast uptake, were simultaneously visualized.
27958688 Results of surgical interventions for critical limb ischemia due to vasculitis or collagen 2017 Aug BACKGROUND: In this study, we aimed to clarify both systemic and local prognosis after surgical interventions for critical limb ischemia (CLI) due to vasculitis or connective tissue related disease, and to search for any risk factors that can worsen the prognosis. METHODS: One hundred and ninety three patients that underwent surgical interventions for CLI between 2005 and 2014 were followed up for a median of 2.7 years. The patients were grouped into a group with vasculitis or connective tissue related disease (V) or with atherosclerosis (control: C). Two groups were retrospectively reviewed and compared. RESULTS: Thirty-one patients were grouped into the V group. At three years after intervention, V group showed significantly higher survival rate compared to C group (89% vs. 73%). On the other hand, limb survival rate after bypass surgery was significantly lower (74% vs. 94%), due to lower patency of the bypassed graft. Within V group, preoperative skin perfusion pressure of lower than 20 mmHg showed significantly worse prognosis of the limb. (HR 1.8; P=0.01) Regarding specific diseases, systemic scleroderma, rheumatoid arthritis and systemic lupus erythematosus tended to show worse prognosis. CONCLUSIONS: Patients with CLI due to vasculitis or connective tissue related disease have a longer life expectancy with lower limb salvage rate that can lead to low quality of the remaining life.
27321428 Experimental transmission of systemic AA amyloidosis in autoimmune disease and type 2 diab 2016 Nov 1 AA amyloidosis is a protein misfolding disease characterized by extracellular deposition of amyloid A (AA) fibrils. AA amyloidosis has been identified in food animals, and it has been postulated that AA amyloidosis may be transmissible to different animal species. Since the precursor protein of AA fibrils is serum amyloid A (SAA), which is an inflammatory acute phase protein, AA amyloidosis is considered to be associated with inflammatory diseases such as rheumatoid arthritis. Chronic diseases such as autoimmune disease and type 2 diabetes mellitus could be potential factors for AA amyloidosis. In this study, to examine the relationship between the induction of AA amyloidosis and chromic abnormalities such as autoimmune disease or type 2 diabetes mellitus, amyloid fibrils from mice, cattle, or chickens were experimentally injected into disease model mice. Wild-type mice were used as controls. The concentrations of SAA, IL-6, and IL-10 in autoimmune disease model mice were higher than those of control mice. However, induction of AA amyloidosis in autoimmune disease and type 2 diabetes mellitus model mice was lower than that in control mice, and the amount of amyloid deposits in the spleens of both mouse models was lower than that of control mice according to Congo red staining and immunohistochemistry. These results suggest that factors other than SAA levels, such as an inflammatory or anti-inflammatory environment in the immune response, may be involved in amyloid deposition.
27708949 Differential diagnosis of elevated erythrocyte sedimentation rate and C-reactive protein l 2015 Dec OBJECTIVE: In the case of high erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, the diagnosis of the underlying disease can be challenging especially in serologically unrevealing patients who have nonspecific clinical findings. We aimed to investigate the final distribution of definitive diagnoses in patients who initially presented with nonspecific clinical findings and sustained elevations in serum ESR/CRP levels. MATERIAL AND METHODS: The medical records of patients hospitalized in a rheumatology clinic between January 2010 and January 2011 were retrospectively analyzed. The patients were classified into two main groups: those with previously diagnosed underlying rheumatic disease (RD) and those without. The groups were analyzed for the final distribution of definitive diagnoses. RESULTS: Out of 112 patients in the general study population, 47 had a previous RD and 65 had no previous history of RD. In these 65 patients, the most common etiology of nonspecific elevations in ESR/CRP levels was new onset RD (52.3%). Polymyalgia rheumatica (PMR) was the most common new onset RD (38% of all new onset RD) followed by seronegative rheumatoid arthritis. The incidences of infections and malignancies were 24.6% and 9.2%, respectively. CRP levels were significantly higher in infections when compared with new onset RD or malignancies (p<0.05). In patients with previous RD, the flare of the underlying disease was the most common etiology of nonspecific elevations in ESR/CRP levels (n=39, 83%, 20 female/19 male). CONCLUSION: Extraordinarily high levels of serum CRP in a patient with nonspecific clinical findings should raise suspicion for non-rheumatic diagnoses, such as infection and malignancy, even in the presence of a previously diagnosed RD. Advanced radiological investigation is justified in these cases to rule out malignancy.
27372916 Ingested (oral) rituximab inhibits EAE. 2016 Sep BACKGROUND: Blocking CD20 can inhibit autoimmune diseases such as multiple sclerosis (MS) and rheumatoid arthritis (RA). OBJECTIVE: We examined whether an antibody against CD20, rituximab (RTX) (Rituxan®), used clinically in oncology, MS and RA would have similar anti-inflammatory effects in EAE after oral administration. DESIGN/METHODS: B6 mice were immunized with MOG peptide 35-55 and gavaged with control saline or RTX during ongoing disease. Splenocytes or CD4(+) T cells from control fed or RTX fed mice were adoptively transferred into active MOG peptide 35-55 immunized recipient mice during ongoing disease. Actively fed and recipient mice were examined for disease inhibition, inflammation, and cytokine responses. RESULTS: Ingested (oral) RTX inhibited ongoing disease and decreased inflammation. Adoptively transferred cells from RTX fed donors protected against actively induced disease and decreased inflammation. There was a decrease in Th1-like cytokines IFN-γ and IL-12, IL-17 and TNF-α in active fed and adoptively treated recipients without upregulation of counter-regulatory cytokines. CONCLUSIONS: Ingested (orally administered) RTX can inhibit disease, CNS inflammation, decrease pro-inflammatory IL-17 and Th1-like cytokines without increases in Th2-like anti-inflammatory cytokines.
27330933 Management of Widespread Skin Thickening in Diffuse Systemic Sclerosis. 2016 Mar Skin thickening is one of the early organ manifestations of systemic sclerosis (SSc) and has a great impact on quality of life (QOL) as well as overall daily living in patients with SSc. The dynamic changes that occur as the disease progresses and as other organs become further involved present the treating physician with therapeutic challenges. Hence, when considering drug therapy for skin disease, the treating physician should consider a number of factors including disease duration, the rate of skin thickening, the extent of disease progression, organ involvements, and patient-related outcome measures, all of which impact the type of treatments considered. For early diffuse skin disease, we prefer the use of methotrexate (MTX). And when there is evidence of lung involvement or tendon friction rubs (given its association with ILD development), we tend to shift to the use of mycophenolate or cyclophosphamide because these agents have been shown efficacious for the specific indication of lung disease in SSc. We have managed joint disease, on the other hand when present, with MTX or other DMARDs, as well as the use of biologics when there is evidence of inflammatory polyarthritis or rheumatoid arthritis overlap. While the treatment of myositis in the setting of SSc can present a therapeutic dilemma, reluctantly, we may use steroids along with MTX, mycophenolate, intravenous immunoglobulin (IV-Ig), or rituximab. Ongoing clinical trials investigating the use of tocilizumab, abatacept, and other agents offer promising potential therapies. Great strides have been made in treating skin disease in SSc. And with recent trials focusing on early SSc disease, this will allow for a greater insight into the mechanisms underlying SSc especially as it relates to skin, and the expansion of future treatment options in this field.
27324990 Syk Inhibition Induces Platelet Dependent Peri-islet Hemorrhage in the Rat Pancreas. 2016 Oct Spleen tyrosine kinase (Syk) is a nonreceptor tyrosine kinase that is an important signaling enzyme downstream of immunoreceptors containing an intracellular immunoreceptor tyrosine activating motif (ITAM). These receptors encompass a wide variety of biological functions involved in autoimmune disease pathogenesis. There has been considerable interest in the development of inhibitors of the Syk pathway for the treatment of rheumatoid arthritis and systemic lupus erythematosus. We report that Syk inhibition mechanistically caused peri-islet hemorrhages and fibrin deposition in the rat pancreas and that this finding is due to a homeostatic functional defect in platelets. In more limited studies, similar lesions could not be induced in mice, dogs, and cynomolgus monkeys at similar or higher plasma drug concentrations. Irradiation-induced thrombocytopenia caused a phenotypically similar peri-islet pancreas lesion and the formation of this lesion could be prevented by platelet transfusion. In addition, Syk inhibitor-induced lesions were prevented by the coadministration of prednisone. A relatively greater sensitivity of rat platelets to Syk inhibition was supported by functional analyses demonstrating rat-specific differences in response to convulxin, a glycoprotein VI agonist that signals through Syk. These data demonstrate that the Syk pathway is critical in platelet-endothelial cell homeostasis in the peri-islet pancreatic microvasculature in rats.
27307714 Patient attitudes and understanding about biosimilars: an international cross-sectional su 2016 OBJECTIVE: To understand the levels of awareness, usage, and knowledge of biosimilars among patients, caregivers, and the general population in the US and the European Union; perceptions of biosimilars compared to originator biologics; perceived benefits and drawbacks of clinical trials; and whether advocacy groups impact patients' willingness to try a biosimilar. METHODS: An international survey was conducted which contained up to 56 closed-ended (requiring yes/no or ranking answers) and open-ended questions, depending on the population assigned. The survey was divided into distinct sections, including medication-class awareness, usage, and knowledge about biologic and biosimilar therapies; perceptions of clinical trials; and involvement in advocacy groups. Interviews were conducted in adults categorized as: 1) diagnosed: patients with inflammatory bowel disease including Crohn's disease and ulcerative colitis, rheumatoid arthritis, psoriasis, breast cancer, lung cancer, colorectal cancer, or non-Hodgkin's lymphoma; 2) diagnosed advocacy: individuals with these diseases who participated in patient support groups; 3) caregiver: has a loved one with these conditions and is involved in medical decisions; 4) general population: aged 18-64 years, without these conditions. Statistical analyses among groups within a region (US or EU) used column proportions test with a 95% confidence interval. RESULTS: In all, 3,198 individuals responded. Awareness about biologic therapies was significantly higher in diagnosed, diagnosed advocacy, and caregiver groups (45%-78%) versus general population (27%; P<0.05). Across all groups, awareness of biosimilars was low; only 6% of the general population reported at least a general impression of biosimilars. Awareness was significantly higher in the diagnosed advocacy group (20%-30%; P<0.05). Gaps in knowledge about biosimilars included safety, efficacy, and access to these agents. Respondents had generally positive perceptions of clinical trials, although barriers to participation were identified. CONCLUSION: An immediate need exists for patient education about biosimilars and clinical trials to ensure educated and informed decisions are made about biosimilar use.
27232337 Alpha 1 Antitrypsin Inhibits Dendritic Cell Activation and Attenuates Nephritis in a Mouse 2016 Systemic lupus erythematosus (SLE) is an autoimmune disorder with a worldwide distribution and considerable mortality and morbidity. Although the pathogenesis of this disease remains elusive, over-reactive dendritic cells (DCs) play a critical role in the disease development. It has been shown that human alpha-1 antitrypsin (hAAT) has protective effects in type 1 diabetes and rheumatoid arthritis mouse models. In the present study, we tested the effect of AAT on DC differentiation and functions, as well as its protective effect in a lupus-prone mouse model. We showed that hAAT treatment significantly inhibited LPS (TLR4 agonist) and CpG (TLR9 agonist) -induced bone-marrow (BM)-derived conventional and plasmacytoid DC (cDC and pDC) activation and reduced the production of inflammatory cytokines including IFN-I, TNF-α and IL-1β. In MRL/lpr mice, hAAT treatment significantly reduced BM-derived DC differentiation, serum autoantibody levels, and importantly attenuated renal pathology. Our results for the first time demonstrate that hAAT inhibits DC activation and function, and it also attenuates autoimmunity and renal damage in the MRL/lpr lupus model. These results imply that hAAT has a therapeutic potential for the treatment of SLE in humans.
27083387 Clinical importance of nonsteroidal anti-inflammatory drug enteropathy: the relevance of t 2016 Sep The pathogenesis of nonsteroidal anti-inflammatory drug (NSAID) enteropathy is still unclear, and consequently, there is no approved therapeutic strategy for ameliorating such damage. On the other hand, molecular treatment strategies targeting tumor necrosis factor (TNF) exerts beneficial effects on NSAID-induced intestinal lesions in rodents and rheumatoid arthritis patients. Thus, TNF appears to be a potential therapeutic target for both the prevention and treatment of NSAID enteropathy. However, the causative relationship between TNF and NSAID enteropathy is largely unknown. Currently approved anti-TNF agents are highly expensive and exhibit numerous side effects. Hence, in this review, the pivotal role of TNF in NSAID enteropathy has been summarized and plant-derived polyphenols have been suggested as useful alternative anti-TNF agents because of their ability to suppress TNF activated inflammatory pathways both in vitro and in vivo.
27019294 Inflammatory effects of TNFα are counteracted by X-ray irradiation and AChE inhibition in 2016 Nov 25 As a means to analyze anti-inflammatory effects by radiation and/or by cholinergic mechanisms, we found that cultured primary human osteoblasts express most cholinergic components. After X-ray irradiation, their level of acetylcholinesterase (AChE) was strongly elevated. As a 3D model, we cultured mesenchymal stem cells isolated from E11 mouse embryos as micromass nodules, and differentiated them into chondro- and osteoblasts. They were stimulated by 5 or 10 ng/ml of the inflammatory cytokine TNF-α to mimic an inflammatory condition in vitro, before exposure to 2 Gy X-rays. Effects on chondro- and osteoblasts of TNF-α, of X-rays, or both were analysed by Alcian Blue, or Alizarin Red staining, respectively. Acetylcholinesterase (AChE) activity was visualized histochemically. The results showed that treatment with TNF-α affected cartilage and bone formation in vitro, while X-rays reversed the effects of TNF-α. After irradiation, both AChE and alkaline phosphatase (ALP) activities, a marker for bone mineralization, were raised, suggesting that X-rays stimulated cholinergic mechanisms during calcification. Notably, the TNFα-effects on cultures were also counterbalanced after AChE activity was blocked by BW284c51. These findings suggest a complex crosstalk between radiation, cholinergic and inflammatory mechanisms, which could have wide significances, e.g. for understanding rheumatoid arthritis.
27004059 Anti-inflammatory activity of Euphorbia aegyptiaca extract in rats. 2016 Jan BACKGROUND: There were no studies on the anti-inflammatory activity of Euphorbia aegyptiaca, though it is commonly used by Sudanese herbalists in the treatment of rheumatoid arthritis. OBJECTIVES: To determine phytochemical constituents of Euphorbia aegyptiacaTo investigate the anti-inflammatory activity of Euphorbia aegyptiaca in rats. METHODOLOGY: Plant material was extracted by ethanol and phytochemical screening was done according to standard methods. The thickness of Albino rats' paws were measured before injection of 0.1 ml of 1% formalin in the sub planter region and then, 1, 2, 3, 4 and 24 hours after oral dose of ethanolic extract of Euphorbia aegyptiaca at a rate of 400mg/kg, 800mg/kg, indomethacin (5mg/kg) and normal saline (5ml/kg). Edema inhibition percentage (EI%) and mean paw thickness (MPT) were measured in the different groups and compared using appropriate statistical methods. RESULTS: The phytochemical screening revealed the presence of saponins, cumarins, flavonoids, tannins, sterols, triterpenes, and absence of alkaloids, anthraquinones glycosides and cyanogenic glycosides. The mean of EI% of rats treated with indomethacin at a dose of 5 mg/kg over different time intervals (64.0%) was significantly lower compared to those treated with Euphorbia aegyptiaca at a dose of 800 mg/kg (75.0%, P< 0.001), but higher compared to rats treated at higher dose of 400 mg/kg (57.4%, P< 0.001). In contrast, MPT of rats treated with indomethacin at a dose of 5 mg/kg (6.5±1.1 mm) was significantly higher compared to those treated with Euphorbia aegyptiaca at a dose of 800 mg/kg (6.1±.7 mm, P< 0.001) as well as 400 mg/kg (5.9±.5, P< 0.001). CONCLUSION: Euphorbia aegyptiaca ethanolic extract has a sustained dose-dependent anti-inflammatory activity.
26962001 HDAC2 regulates FoxO1 during RANKL-induced osteoclastogenesis. 2016 May 15 The bone-resorbing osteoclast (OC) is essential for bone homeostasis, yet deregulation of OCs contributes to diseases such as osteoporosis, osteopetrosis, and rheumatoid arthritis. Here we show that histone deacetylase 2 (HDAC2) is a key positive regulator during receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and bone resorption. Bone marrow macrophages (BMMs) showed increased HDAC2 expression during osteoclastogenesis. HDAC2 overexpression enhanced, whereas HDAC2 deletion suppressed osteoclastogenesis and bone resorption using lentivirus infection. Mechanistically, upon RANKL activation, HDAC2 activated Akt; Akt directly phosphorylates and abrogates Forkhead box protein O1 (FoxO1), which is a negative regulator during osteoclastogenesis through reducing reactive oxygen species. HDAC2 deletion in BMMs resulted in decreased Akt activation and increased FoxO1 activity during osteoclastogenesis. In conclusion, HDAC2 activates Akt thus suppresses FoxO1 transcription results in enhanced osteoclastogenesis. Our data imply the potential value of HDAC2 as a new target in regulating osteoclast differentiation and function.
26953630 The microbiome-systemic diseases connection. 2016 Nov The human microbiome consists of all microorganisms occupying the skin, mucous membranes and intestinal tract of the human body. The contact of the mucosal immune system with the human microbiome is a balanced interplay between defence mechanisms of the immune system and symbiotic or pathogenic microbial factors, such as microbial antigens and metabolites. In systemic autoimmune diseases (SADs) such as rheumatoid arthritis, systemic lupus erythematosus and Sjögren's syndrome, the immune system is deranged to a chronic inflammatory state and autoantibodies are an important hallmark. Specific bacteria and/or a dysbiosis in the human microbiome can lead to local mucosal inflammation and increased intestinal permeability. Proinflammatory lymphocytes and cytokines can spread to the systemic circulation and increase the risk of inflammation at distant anatomical sites, such as the joints or salivary glands. Increased intestinal permeability increases antigen exposure and the risk of autoantibody production. If the human microbiome indeed plays such a critical role in SADs, this finding holds a great promise for new therapeutic strategies, such as diet interventions and probiotics and prebiotics. This review provides a background on the human microbiome and mucosal immunity in the gut and oral cavity and gives a summary of the current knowledge on the microbiome-SADs connection.
26945832 Interleukin 21 as a new possible player in pemphigus: Is it a suitable target? 2016 May Pemphigus is a rare autoimmune disease, which could be fatal without treatment. Recently, target therapy is increasingly being used in different autoimmune diseases. However, there are limited studies associated with target therapy in pemphigus. In this study, it was tried to identify the role of interleukin (IL) -21 in patients with pemphigus. Based on the available studies on the role of IL-21 associated with several cells, including T cells, B cells, natural killer (NK) cells, natural killer T (NKT) cells, mast cells as well as regulatory B cells and regulatory T cells, the possible roles of this cytokine in pemphigus were discussed in detail. It was found that IL-21 is a crucial cytokine associated with pemphigus disease, which has not been discussed in this disease yet. It is able to promote T helper (Th) 2, Th17, T follicular helper (Tfh), CD8+ cytotoxic T lymphocytes (CTLs), NK and NKT cells. It also causes the production of immunoglobulin (Ig)G in addition to the decrease of Tregs. All the mentioned alterations seem to be involved in disease progression via different signaling pathways. Inhibition of these changes must cause improvement of disease severity. By inhibition of IL-21 or its receptor, it is expected that patients with severe pemphigus experience relative and gradual improvement. This inhibition could be induced by tofacitinib, which was approved by the US Food and Drug Administration as a treatment for rheumatoid arthritis patients, or anti-IL-21 monoclonal antibody, NNC114-0006. However, more studies are needed to confirm it as a promising therapy.
26907827 Emerging therapies in systemic lupus erythematous: from clinical trial to the real life. 2016 Systemic lupus erythematous (SLE) is a chronic autoimmune disease characterised by multisystem involvement and a relapsing remitting course. SLE is a highly heterogeneous condition, with wide variations in both the presentation and severity of disease and the biological markers identified. The use of biologics in SLE has lagged behind that of other rheumatological conditions such as rheumatoid arthritis, in part due to the diverse clinical manifestations of SLE, making it difficult to design appropriate trials for novel treatments. As such, broad immunosuppressive treatment regimens are still widely used in SLE. Nevertheless, in recent years, elucidation of some aspects of SLE pathogenesis have allowed the development of therapies targeted at molecular mediators of SLE. This review provides an update of biological available therapies and those currently under development.
26820487 Benefits of Using CD45RA and CD28 to Investigate CD8 Subsets in Kidney Transplant Recipien 2016 Mar The deleterious role of CD8 T cells in kidney graft outcome has regained interest over the years, and memory T cells are considered as one of the main hurdles to achieve transplantation success. Monitoring the CD8 immune response in transplant recipients involved a heterogeneous combination of markers, but the justification of their choice is rarely stated. Whereas the number of parameters is not an issue in phenotypic analysis, functional assays have to accommodate the cell number with the narrowing of the subset. The aim of the study was to investigate the similarities and differences of the subsets identified using three nomenclatures (CD45RA and CCR7/CD27/CD28) in kidney transplant recipients with stable graft function. We found that all three nomenclatures can identify naïve and effector memory (EM) rheumatoid arthritis T cell CD8 with similar features. Whereas CM CD8 could only be documented using CCR7 and CD45RA, the characteristics of EM CD8 will differ according to the nomenclature. We found that the use of the CD45RA and CD28 gives the benefit of examining two EM populations at early and late differentiation states. This systematic comparison provides a cohesive layout of the advantages of using these nomenclature strategies in kidney transplant recipients to guide the choice of their use.
26697674 Progress on mechanism of Tripterygium wilfordii-induced liver injury and detoxification me 2015 Jul Tripterygium wilfordii has exihibited multiple pharmacological activities, such as anti-inflammatory, immune modulation, anti-tumor and anti-fertility. T. wilfordii have been used for the therapy of inflammation and autoimmune diseases including rheumatoid arthritis, immune complex nephritis and systemic lupus erythematosus clinically. However, it is well known that T. wilfordii has small margin between the therapeutic and toxic doses and could cause serious injury on digestive, reproductive and urogenital systems. Among all the organs, liver is one of the most remarkable targets of T. wilfordii-induced toxicities, and the damage is more serious than others. It is generally accepted that T. wilfordii-induced liver injury is a result of the combined effects of toxic elements of T. wilfordii. It is reported in several studies that the mechanism of T. wilfordii-induced liver injury may be related to lipid peroxidation, cell apoptosis and immune damage, and so on. Licorice is one of the most commonly used Chinese herbal medicine, with effects of heat- clearing and detoxicating, anti-inflammatory and hepatoprotective, reconciling various drugs, and so on. Licorice often accompany T. wilfordii in clinical application which can significantly reduce the liver injury induced by T. wilfordii. The attenuated effect is exact, but the mechanism is still a lack of in-depth study. This paper reviews the studies on T. wilfordii-induced liver injury and the related mechanism as well as licorice and other traditional Chinese medicine accompany T. wilfordii to reduce the injury in recent years, so as to provide reference for related research in the future.
26608204 Circulating Extracellular microRNA in Systemic Autoimmunity. 2015 MicroRNAs (miRNAs) are differentially regulated in healthy, activated, inflamed, neoplastic, or otherwise pathological cells and tissues. While their main functions are executed intracellularly, many miRNAs can reproducibly be detected extracellularly in plasma and serum. This circulating, extracellular miRNA is protected against degradation by complexation with carrier proteins and/or by being enclosed in subcellular membrane vesicles. This, together with their tissue- and disease-specific expression, has fuelled the interest in using circulating microRNA profiles as harbingers of disease, i.e., as diagnostic analytes and as clues to dysregulated pathways in disease. Many studies show that inflammation and immune dysregulation, e.g., in autoimmune diseases, are associated with distinct miRNA expression changes in targeted tissues and in innate and adaptive immunity cells such as lymphocytes, natural killer cells, neutrophil granulocytes, and monocyte-macrophages. Exploratory studies (only validated in a few cases) also show that specific profiles of circulating miRNAs are associated with different systemic autoimmune diseases including systemic lupus erythematosus (SLE), systemic sclerosis, and rheumatoid arthritis. Even though the link between cellular alterations and extracellular profiles is still unpredictable, the data suggest that circulating miRNAs in autoimmunity may become diagnostically useful. Here, we review important circulating miRNAs in animal models of inflammation and in systemic autoimmunity and summarize some proposed functions of miRNAs in immune regulation and dysregulation. We conclude that the studies suggest new hypotheses and additional experiments, and that further diagnostic development is highly dependent on analytical method development and on obtaining sufficient numbers of uniformly processed samples from clinically well-characterized patients and controls.
26555659 [Indications and contraindications for radiosynoviorthesis]. 2015 Nov BACKGROUND: Radiosynoviorthesis (RSO) provides a simple method for the treatment of patients with chronic synovitis and has only few side effects. OBJECTIVES: Evidence-based indications and contraindications for performing RSO based on the current literature are presented. MATERIAL AND METHODS: Published information on the indications and contraindications for performing RSO in chronic synovitis were analyzed and summarized. RESULTS: According to the guideline recommendations of the German Society of Rheumatology indications for RSO are given in patients with rheumatoid arthritis, seronegative spondyloarthropathy, crystal arthropathy, villonodular synovitis and hemophilia with recurrent joint bleeding. Osteoarthritis with documented reactive synovitis is also regarded as an indication in the guidelines of the nuclear medicine societies. The European League Against Rheumatism (EULAR) and the German Society of Rheumatology (DGRh) have given no recommendations for using RSO in osteoarthritis. Given the correct indications RSO shows high success rates. CONCLUSION: The effects of RSO with the named secondary side effects last on average for 5 years. Crucial for the success of RSO are the correct indications, the correct timing and combination with other therapeutic procedures, such as surgical synovectomy.