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ID PMID Title PublicationDate abstract
30270548 Expression of ETS1 and LEF1 in salivary glands of Sjögren syndrome patients. 2019 Jan OBJECTIVE: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease affecting exocrine glands, thereby causing dry mouth and eyes (sicca). Our objective was to determine the expression of pSS pathogenic biomarker MMP9 and its putative transcription factors ETS1 and LEF1, in labial salivary glands of pSS patients. METHODS: Sicca patients were assigned to three groups based on focus score (FS): non-pSS sicca (i.e., GR1 [FS = 0] and GR2 [0 < FS < 1]) and pSS (i.e., GR3 [FS ≥ 1]). We determined the mRNA and protein expression of MMP9, ETS1, and LEF1 in salivary gland biopsies. Also, ETS1-CD4 and LEF1-CD4 co-expression analyses were performed. RESULTS: The mRNA expression of MMP9, ETS1, and LEF1 was upregulated in GR3 compared to GR1 (p < 0.01). Most GR3 salivary gland areas had moderate to high MMP9, ETS1, and LEF1 protein expression compared to GR1 and GR2. Further, ETS1-CD4 and LEF1-CD4 dual staining demonstrated that both salivary gland epithelial cells and lymphocytic infiltrates had increased levels of ETS1 and LEF1. Moreover, there was a strong correlation between ETS1(+)-CD4(-) and LEF1(+)-CD4(-) cells. CONCLUSION: These results suggest, for the first time, a concerted increase in ETS1 and LEF1 expression in salivary gland epithelial cells of pSS patients that is reflective of the etiopathogenesis of pSS.
29779010 Low miR200b-5p levels in minor salivary glands: a novel molecular marker predicting lympho 2018 Aug OBJECTIVES: Development of non-Hodgkin's lymphoma (NHL) is the major adverse outcome of Sjögren's syndrome (SS) affecting both morbidity and mortality. Preliminary evidence suggested that, although not deregulated compared with sicca controls, miR200b-5p levels are decreased in the minor salivary glands (MSGs) of SS patients with NHL. The aim of the current study was to evaluate the MSG expression of miR200b-5p in SS-associated NHLs and its potential predictive value for the identification of patients with SS susceptible to develop NHL. METHODS: miR200b-5p expression was investigated in MSG tissues of patients with SS who were at: (A) low risk and did not develop NHL during follow-up (n=27; median follow-up time on biopsy performance, range: 8.9 years, 1.33-14 years), (B) high-risk and diagnosed with NHL during follow-up (prelymphoma; n=17; median follow-up to until lymphoma diagnosis, range: 3.67 years, 0.42-8.5 years) and (C) had NHL (n=35), as well as non-SS sialadenitis controls (sarcoidosis and hepatitis C virus (HCV) infection, four each). The differential miR200b-5p expression, correlations with disease features and its discriminative/predictive value, was evaluated by appropriate statistical approaches. RESULTS: The MSG levels of miR200b-5p were significantly downregulated in patients with SS who will develop or have NHL and strongly discriminated (p<0.0001) them from those without lymphoma or non-SS sialadenitis. Furthermore, they were reduced long before clinical onset of lymphoma, did not significantly change on transition to lymphoma and, importantly, were proved strong independent predictors of patients who will develop NHL (p<0.0001). CONCLUSIONS: These findings support that miR200b-5p levels in MSGs represent a novel predictive and possibly pathogenetic mechanism-related factor for the development of SS-associated NHL, since its expression is impaired years before lymphoma clinical onset.
29432648 Pilocarpine and artificial saliva for the treatment of xerostomia and xerophthalmia in Sjà 2018 Nov BACKGROUND: Sjögren syndrome (SS) is associated with xerostomia and xerophthalmia. Pilocarpine has been shown to stimulate the secretion of saliva. OBJECTIVES: To investigate and compare the efficacy of pilocarpine and artificial saliva as symptomatic treatments for xerostomia and xerophthalmia in patients with SS. METHODS: A double-blind randomized controlled study was performed. A total of 72 patients with SS were assigned randomly to receive 10 drops of pilocarpine (5 mg) or 10 drops of artificial saliva orally, three times daily for 12 weeks. Whole saliva and tear flow were evaluated at baseline and periodically throughout the study to provide a global assessment of dryness and to report any adverse effects. RESULTS: Patients receiving pilocarpine had a statistically significant improvement in their salivary flow (P < 0·001), lacrimal flow (P < 0·001) and their subjective global assessment (P < 0·001), compared with patients who received artificial saliva. The most common side-effects were sialorrhoea and nausea. CONCLUSIONS: Pilocarpine is more effective than artificial saliva for enhancing salivary and lacrimal secretion in patients with SS. This is the first study to compare the efficacy of pilocarpine and artificial saliva for the treatment of xerostomia and xerophthalmia in SS.
29370826 BANK1 alters B cell responses and influences the interactions between B cells and induced 2018 Jan 25 BACKGROUND: Functional variants of the B cell gene, B cell scaffold protein with ankyrin repeats 1 (BANK1) contribute to rheumatoid arthritis (RA) susceptibility, but their influences on B cell responses are unclear. Moreover, the function of induced T regulatory cells (iTregs) in the inflammatory milieu in a collagen-induced arthritis (CIA) model is unknown. This study was performed to investigate the roles of BANK1 in CIA and the interaction between B cells and iTregs. METHODS: The changes in BANK1 mRNA and protein levels and their correlation with disease severity in CIA were determined. Next, the antigen-presenting function and autoantibody production in B cells were evaluated by co-culture with effector T cells and iTregs, respectively, both in vitro and in vivo. Then, the mechanisms underlying these interactions were studied by adding neutralizing antibodies or transwell inserts and by adoptive transfer to B-cell-depleted CIA mice. RESULTS: The BANK1 level decreased in the peripheral blood, spleen and lymph nodes of CIA mice, particularly during the acute stage of arthritis, and exhibited negative correlation with disease severity and autoantibody production. B cell responses were enhanced by this decrease. B cells from CIA mice (CIA-B cells) promoted iTreg differentiation, proliferation and cytotoxic T lymphocyte-associated protein-4 (CTLA-4) expression. Meanwhile, BANK1 expression in CIA-B cells increased after co-culture with iTregs, limiting B cell responses. All these interactions depended on cell contact with CTLA-4-overexpressing iTregs but were independent of CTLA-4 cytokine. CONCLUSION: Decreased BANK1 expression promotes B cell responses, resulting in an increased antigen presentation ability and autoantibody production that subsequently influences the communication between B cells and iTregs through a cell-contact-dependent and CTLA-4- cytokine-independent mechanism in CIA mice.
30361689 IL-6, IL-17 and Stat3 are required for auto-inflammatory syndrome development in mouse. 2018 Oct 25 Auto-inflammatory syndrome, a condition clinically distinct from rheumatoid arthritis, is characterized by systemic inflammation in tissues such as major joints, skin, and internal organs. Autonomous innate-immune activation is thought to promote this inflammation, but underlying pathological mechanisms have not been clarified nor are treatment strategies established. Here, we newly established a mouse model in which IL-1 signaling is conditionally activated in adult mice (hIL-1 cTg) and observed phenotypes similar to those seen in auto-inflammatory syndrome patients. In serum of hIL-1 cTg mice, IL-6 and IL-17 levels significantly increased, and signal transducer and activator of transcription 3 (Stat3) was activated in joints. When we crossed hIL-1 cTg with either IL-6- or IL-17-deficient mice or with Stat3 conditional knockout mice, phenotypes seen in hIL-1 cTg mice were significantly ameliorated. Thus, IL-6, IL-17 and Stat3 all represent potential therapeutic targets for this syndrome.
29976231 Hydroxychloroquine prescription trends and predictors for excess dosing per recent ophthal 2018 Jul 5 BACKGROUND: Hydroxychloroquine (HCQ) retinopathy may be more common than previously recognized; recent ophthalmology guidelines have revised recommendations from ideal body weight (IBW)-based dosing to actual body weight (ABW)-based dosing. However, contemporary HCQ prescribing trends in the UK remain unknown. METHODS: We examined a UK general population database to investigate HCQ dosing between 2007 and 2016. We studied trends of excess HCQ dosing per ophthalmology guidelines (defined by exceeding 6.5 mg/kg of IBW and 5.0 mg/kg of ABW) and determined their independent predictors using multivariable logistic regression analyses. RESULTS: Among 20,933 new HCQ users (78% female), the proportions of initial HCQ excess dosing declined from 40% to 36% using IBW and 38% to 30% using ABW, between 2007 and 2016. Among these, 47% of women were excess-dosed (multivariable OR 12.52; 95% CI 10.99-14.26) using IBW and 38% (multivariable OR 1.98; 95% CI,1.81-2.15) using ABW. Applying IBW, 37% of normal and 44% of obese patients were excess-dosed; however, applying ABW, 53% of normal and 10% of obese patients were excess-dosed (multivariable ORs = 1.61 and 0.1 (reference = normal); both p < 0.01). Long-term HCQ users showed similar excess dosing. CONCLUSION: A substantial proportion of HCQ users in the UK, particularly women, may have excess HCQ dosing per the previous or recent weight-based guidelines despite a modest decline in recent years. Over half of normal-BMI individuals were excess-dosed per the latest guidelines. This implies the potential need to reduce dosing for many patients but also calls for further research to establish unifying evidence-based safe and effective dosing strategies.
30116556 Methods to improve medication adherence in patients with chronic inflammatory rheumatic di 2018 OBJECTIVE: Lack of adherence to treatment is frequent in chronic inflammatory rheumatic diseases and is associated with poorer outcomes. The objective of this study was to describe and evaluate interventions that have been proposed to enhance medication adherence in these conditions. METHODS: A systematic literature review was performed in Pubmed, Cochrane, Embase and clinicaltrials.gov databases completed by the rheumatology meeting (ACR, EULAR and SFR) abstracts from last 2 years. All studies in English or French evaluating an intervention to improve medication adherence in chronic inflammatory rheumatic diseases (rheumatoid arthritis (RA), spondyloarthritis (SpA), crystal related diseases, connective tissue diseases, vasculitis and Still's disease) were included. Interventions on adherence were collected and classified in five modalities (educational, behavioural, cognitive behavioural, multicomponent interventions or others). RESULTS: 1325 abstracts were identified and 22 studies were finally included (18 studies in RA (72%), 4 studies in systemic lupus erythematosus (16%), 2 studies in SpA (8%) and 1 study in gout (4%)). On 13 randomised controlled trials (RCT) (1535 patients), only 5 were positive (774 patients). Educational interventions were the most represented and had the highest level of evidence: 8/13 RCT (62%, 1017 patients) and 4/8 were positive (50%). In these studies, each patient was individually informed or educated by different actors (physicians, pharmacists, nurses and so on). Supports and contents of these educational interventions were heterogenous. CONCLUSION: Despite the importance of medication adherence in chronic inflammatory rheumatic disorders, evidence on interventions to improve medication adherence is scarce.
29686987 Recognition and Relevance of Anti-DFS70 Autoantibodies in Routine Antinuclear Autoantibodi 2018 Antinuclear autoantibodies (ANA) displaying a dense fine speckled pattern (DFS, ICAP AC-2) on HEp-2 cells are frequently observed in clinical laboratory referrals, often associated with anti-DFS70 specificity. Anti-DFS70 positive patients rarely develop systemic autoimmune rheumatic disease (SARD), especially in the absence of clinical evidence or additional anti-extractable nuclear antigen (ENA) antibodies, prompting suggestions that an isolated DFS70-specific ENA may be an exclusionary finding for SARD. In this study, the frequency and diagnostic significance of anti-DFS70 autoantibodies was investigated in a community hospital cohort of patients undergoing routine ANA testing. ANA screening was performed by HEp-20-10-based indirect immunofluorescence, followed by ENA profiling using a multiparametric line immunoassay (LIA). Of 6,511 patient samples tested for ANA in 2016, the DFS pattern was identified in 1,758 (27.0%), 720 (41.0%) of which were anti-DFS70 positive by LIA. Of these, 526 (73.1%) revealed isolated anti-DFS70 reactivity, while 194 (26.9%) showed additional ENA specificities. Among 1,038 anti-DFS70 negative or borderline samples, 778 (75.0%) were ENA profile negative, while the remaining 260 (25.0%) showed a varied presence of other ENA specificities. Chart reviews of patients with an isolated anti-DFS70 ANA affirmed that ANA-related SARD is rare in the absence of clinical evidence or other ENA specificities, there being no case thus far identified. Rheumatoid arthritis patients occasionally had an isolated anti-DFS70 ANA and were positive for rheumatoid factor and anti-cyclic citrullinated peptide antibodies. In conclusion, the recognition of a DFS ANA pattern using a mitotic-rich HEp-2 substrate, followed by confirmation of anti-DFS70 specificity should be a routine ANA testing service. Use of an expanded ENA profile and clinical correlation is necessary to affirm the "isolation" of anti-DFS70 as the cause of an ANA. Recognition of isolated anti-DFS70 ANA enables reassurance of patients that SARD is unlikely, thus avoiding referral for more extensive testing. The presence of significant elevations of other ENAs may reflect SARD and warrants close clinical correlation and follow-up.
30511559 Association between interleukin-10 polymorphisms and juvenile idiopathic arthritis: a meta 2022 Feb INTRODUCTION: The aim of this review is to investigate IL-10 polymorphisms (-1082 G/A, -819 C/T, and -592 C/A) and their association with susceptibility to JIA. EVIDENCE ACQUISITION: A meta-analysis was conducted after database search for relevant articles (MEDLINE and EMBASE). EVIDENCE SYNTHESIS: A total of seven studies involving 1495 patients and 1670 controls were considered in the meta-analysis. There was no association between the IL-10 -1082 G/A, -819 C/T, and -592 C/A polymorphisms and JIA in allele contrast and any of the genetic models (allele contrast: odds ratio [OR] 0.90, 95% confidence interval [CI] 0.79-1.02, P=0.09; OR=0.97, 95% CI 0.83-1.13, P=0.68; OR=0.92, 95% CI 0.81-1.06, P=0.24, respectively). In subgroup analysis, none of the subtypes of JIA including systemic, rheumatoid factor (RF)-positive polyarticular, RF-negative polyarticular, and oligoarticular was not significantly associated with IL-10 polymorphism. Meta-analysis of the IL-10 haplotype revealed no association between GCC, ACC, and ATA haplotypes and JIA. CONCLUSIONS: This meta-analysis showed that IL-10 polymorphisms were not associated with risk of JIA.
30455954 Transbronchial lung cryobiopsy: a novel confirmatory tool to diagnose asbestos-related pul 2019 Jan Asbestosis is diagnosed with a combination of historical, clinical and radiological findings in the absence of another cause. Histology is required when uncertainty exists, with lung biopsy via VATs being gold standard. Transbronchial cryobiopsy is becoming increasingly popular for diagnosing interstitial lung disease and may provide sufficient lung sample to demonstrate asbestosis. A 73 year old man presented with dyspnoea on a background of rheumatoid arthritis, previous methotrexate use and asbestos exposure. Examination revealed fine crackles in the mid and lower zones bilaterally without signs of pulmonary hypertension. The presence of pleural plaques and basal interstitial reticulation on HRCT was suggestive of asbestosis but histology was required to differentiate this from rheumatoid or methotrexate associated ILD. Samples of lung tissue were obtained via transbronchial cryobiopsy, demonstrating fibrosis and asbestos fibres consistent with asbestosis. Transbronchial cryobiopsy appears effective in obtaining sufficient parenchymal lung samples to diagnose asbestosis when clinical uncertainty exists.
30401979 Hydroxychloroquine retinopathy - implications of research advances for rheumatology care. 2018 Dec Despite advances in therapy for rheumatic diseases, hydroxychloroquine remains almost universally recommended for the treatment of systemic lupus erythematosus (SLE), and is often used in the management of other rheumatic diseases such as rheumatoid arthritis (RA). However, the major dose-limiting toxicity of hydroxychloroquine is retinopathy that can lead to loss of vision. New highly sensitive screening methods can identify early stages of retinopathy, and studies that include these modalities have indicated a substantially higher prevalence of hydroxychloroquine retinopathy than was previously recognized, resulting in revisions to ophthalmology guidelines and the recommendation of a low dose of hydroxychloroquine for many patients. However, the efficacy of low-dose hydroxychloroquine for treating SLE and other rheumatic diseases is unknown. Further studies are required to establish the effectiveness and retinal safety of the latest hydroxychloroquine treatment recommendations.
30305781 Impact of vegan diets on gut microbiota: An update on the clinical implications. 2018 Oct Numerous studies indicate that microbiota plays an important role in human health. Diet is a factor related to microbiota which also influences human health. The relationships between diet, microbiota, and human health are complex. This review focuses on the current literature on vegan diets and their unique impact on gut microbiota. We also report on the health benefits of a vegan diet for metabolic syndrome, cardiovascular disease, and rheumatoid arthritis concerning relevant impacts from gut microbiota. Despite evidence supporting the clinical relevance of vegan gut microbiota to human health, the whole mechanism awaits further investigation.
30087779 An unusual case of shortness of breath. 2018 Myopathy is a well-known complication of hypercortisolism and commonly involves proximal lower-limb girdle. We report a rare case of Cushing's syndrome in a 60-year-old female presenting with significant respiratory muscle weakness and respiratory failure. She had history of rheumatoid arthritis, primary biliary cirrhosis and primary hypothyroidism and presented with weight gain and increasing shortness of breath. Investigations confirmed a restrictive defect with impaired gas transfer but with no significant parenchymatous pulmonary disease. Respiratory muscle test confirmed weakness of respiratory muscles and diaphragm. Biochemical and radiological investigations confirmed hypercortisolaemia secondary to a left adrenal tumour. Following adrenalectomy her respiratory symptoms improved along with an objective improvement in the respiratory muscle strength, diaphragmatic movement and pulmonary function test. LEARNING POINTS: Cushing's syndrome can present in many ways, a high index of suspicion is required for its diagnosis, as often patients present with only few of the pathognomonic symptoms and signs of the syndrome.Proximal lower-limb girdle myopathy is common in Cushing's syndrome. Less often long-term exposure of excess glucocorticoid production can also affect other muscles including respiratory muscle and the diaphragm leading to progressive shortness of breath and even acute respiratory failure.Treatment of Cushing's myopathy involves treating the underlying cause that is hypercortisolism. Various medications have been suggested to hinder the development of GC-induced myopathy, but their effects are poorly analysed.
29985181 Sarcoidosis and autoimmune diseases: differences, similarities and overlaps. 2018 Sep PURPOSE OF REVIEW: Sarcoidosis is a rare, multisystem granulomatous disease of incompletely understood pathogenesis. Clinically, it shares common features with several systemic and organ-specific autoimmune diseases, although known autoantibodies or useful serologic markers for diagnosis and monitoring of disease activity are lacking. Sarcoidosis can both coexist with or mimic connective tissue diseases or vasculitis. Here, we review possible common etiologic factors between sarcoidosis and autoimmune disease, comparing clinical, laboratory and imaging features. RECENT FINDINGS: Autoimmune diseases may precede or follow the diagnosis of sarcoidosis. Overall, the prevalence of both co-existing is unknown because of limited evidence. The presence of autoantibodies in sarcoidosis should raise suspicion of an underlying autoimmune disease that mimics or co-occurs with sarcoidosis. Silica dust exposure has been associated with an increased prevalence of both sarcoidosis and rheumatoid arthritis. In another study, autoimmune thyroid disease, Sjogren's syndrome and ankylosing spondylitis have been reported to be more frequent in sarcoidosis compared with healthy controls. SUMMARY: A systematic diagnostic work-up is necessary to detect overlapping disease features in patients with sarcoidosis. Immune-modulating therapies need to be taken into account as these can induce paradoxical reactions.
29588555 Insulin Autoimmune Syndrome: a rare case of hypoglycaemia resolving with immunosuppression 2018 Jan We report a case of a 58-year-old male presenting with confusion and hypoglycaemia. There had been no prior exposure to oral hypoglycaemic agents or insulin. He was found to have inappropriate endogenous hyperinsulinaemia. Insulinoma was excluded by detailed endocrine assessment. Insulin antibodies were positive in keeping with a diagnosis of insulin autoimmune syndrome (IAS). He was treated with prednisolone 5mg once daily and nutritional supplements leading to resolution of acute confusion and hypoglycaemic episodes. The patient also had severe psoriasis and following discharge was treated with a variety of immunosuppressant therapies. This was associated with disappearance of insulin antibodies after twelve months of follow up. While it is possible that there was spontaneous resolution of insulin antibodies, we speculate that his prednisolone and immunosuppressant therapy may have suppressed insulin antibody production. There are several well recognised associations with IAS and autoimmune conditions, including Grave's disease, systemic lupus erythematous and rheumatoid arthritis. To our knowledge this is the first reported case of insulin autoimmune syndrome, resolving with immunosuppressant treatment of psoriasis.
29383299 Early Biologic Treatment in Pediatric Crohn's Disease: Catching the Therapeutic Window of 2018 Jan The emergence of mucosal healing as a treatment goal that could modify the natural course of Crohn's disease and the accumulating evidence showing that biologics are most effective in achieving mucosal healing, along with the success of early treatment regimens for rheumatoid arthritis, have led to the identification of early Crohn's disease and development of the concept of catching the therapeutic window during the early disease course. Thus, an increasing number of pediatric gastroenterologists are adopting an early biologic treatment strategy with or without an immunomodulator. Although early biologic treatment is effective, cost and overtreatment are issues that limit its early use. Currently, there are insufficient data on who will benefit most from early biologics, as well as on who will not need early or even any biologics. For now, top-down biologics should be considered for patients with currently known high-risk factors of poor outcomes. For other patients, close, objective monitoring and accelerating the step-up process by means of a treat-to-target approach seems the best way to catch the therapeutic window in early pediatric Crohn's disease. The individual benefits of immunomodulator addition during early biologic treatment should be weighed against its risks and decision on early combination treatment should be made after comprehensive discussion with each patient and guardian.
28532196 Fetal and neonatal involvement in maternal rheumatologic disease. 2018 Aug A pregnancy complicated with rheumatologic diseases can have various influences on the fetus and/or neonate. Maternal systemic lupus erythematosus (SLE) may cause preterm and/or small for gestational age (SGA) delivery and neonatal lupus (NL). Some neonates with NL have congenital heart block (CHB) with increased morbidity and mortality, even requiring pacemakers. Antiphospholipid syndrome may occur with SLE and affect fetal and/or neonatal outcomes. Pregnancy involving primary Sjögren's syndrome (pSS) tends to result in preterm delivery and low birthweight infants. Moreover, CHB is the most challenging complication for neonates delivered by women with pSS. Pregnant women with rheumatoid arthritis (RA) are at an increased risk for delivering a preterm or SGA neonate. In addition, RA drugs may have adverse effects on the fetus and breast-fed neonate. With dermatomyositis/polymyositis, pregnancies are at increased risk for spontaneous abortion, perinatal death, and preterm delivery. At present, overall neonatal survival rates are good for pregnancies involving systemic sclerosis, despite an increased frequency of premature and SGA neonates. In conclusion, maternal rheumatological diseases require careful monitoring to ensure the best possible management for fetal and neonatal outcomes.
30083164 T Follicular Helper-Like Cells in Inflamed Non-Lymphoid Tissues. 2018 T and B cell cooperation normally takes place in secondary lymphoid organs (SLO). However, both cell types are also frequently found in inflamed non-lymphoid tissues. Under certain conditions, these infiltrates develop into ectopic lymphoid structures, also known as tertiary lymphoid tissues, which structurally and functionally fully resemble germinal centers (GCs) in SLO. However, tertiary lymphoid tissue is uncommon in most human autoimmune conditions; instead, relatively unstructured T and B cell infiltrates are found. Recent studies have demonstrated that active T and B cell cooperation can also take place in such unstructured aggregates. The infiltrating cells contain a population of T follicular helper (Tfh)-like cells (also designated "peripheral T helper cells") lacking prototypic Tfh markers like CXCR5 and Bcl-6 but nevertheless expressing high levels of molecules important for B cell help like IL-21 and CD40L. Moreover, Tfh-like cells isolated from inflamed tissues can drive the differentiation of B cells into antibody-secreting cells in vitro. These findings are not restricted to experimental animal models but have been reproduced in rheumatoid arthritis and breast cancer patients. At this point, it is unclear whether T and B cell cooperation outside the ordered structure of the GC fully mirrors the reactions in SLO. However, Tfh-like cells in inflamed tissues are certainly important for the local differentiation of B cells into antibody-secreting cells, and should be considered as an important target for the treatment of autoimmune diseases.
30072865 Implications of Systemic Inflammation and Periodontitis for Major Depression. 2018 Increasing evidence suggests that infection and persistent low-grade inflammation in peripheral tissues are important pathogenic factors in major depression. Major depression is frequently comorbid with systemic inflammatory diseases/conditions such as rheumatoid arthritis, allergies of different types, multiple sclerosis, cardiovascular disease, inflammatory bowel disease, chronic liver disease, diabetes, and cancer, in which pro-inflammatory cytokines are overexpressed. A number of animal studies demonstrate that systemic inflammation induced by peripheral administration of lipopolysaccharide increases the expression of pro-inflammatory cytokines in both the periphery and brain and causes abnormal behavior similar to major depression. Systemic inflammation can cause an increase in CNS levels of pro-inflammatory cytokines associated with glial activation, namely, neuroinflammation, through several postulated pathways. Such neuroinflammation can in turn induce depressive moods and behavioral changes by affecting brain functions relevant to major depression, especially neurotransmitter metabolism. Although various clinical studies imply a causal relationship between periodontitis, which is one of the most common chronic inflammatory disorders in adults, and major depression, the notion that periodontitis is a risk factor for major depression is still unproven. Additional population-based cohort studies or prospective clinical studies on the relationship between periodontitis and major depression are needed to substantiate the causal link of periodontitis to major depression. If such a link is established, periodontitis may be a modifiable risk factor for major depression by simple preventive oral treatment.
29449068 Chemokines beyond chemo-attraction: CXCL10 and its significant role in cancer and autoimmu 2018 Sep Chemokines are mostly known for their chemotactic properties, and less for their ability to direct the biological function of target cells, including T cells. The current review focuses on a key chemokine named CXCL10 and its role in directing the migratory propertied and biological function of CD4+ and CD8+ T cells in the context of cancer and inflammatory autoimmunity. CXCR3 is a chemokine receptor that is abundant on CD4+ T cells, CD8+ T cells and NK cells. It has three known ligands: CXCL9, CXCL10 and CXCL11. Different studies, including those coming form our laboratory, indicated that aside of attracting CD8+ and CD4+ effector T cells to tumor sites and sites of inflammation CXCL10 directs the polarization and potentiates the biological function of these cells. This makes CXCL10 a "key driver chemokine" and a valid target for therapy of autoimmune diseases such as Inflammatory Bowl's Disease, Multiple Sclerosis, Rheumatoid arthritis and others. As for cancer this motivated different groups, including our group to develop CXCL10 based therapies for cancer due to its ability to enhance T-dependent anti cancer immunity. The current review summarizes these findings and their potential translational implication.