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ID PMID Title PublicationDate abstract
32891685 Abnormal membrane-bound and soluble programmed death ligand 2 (PD-L2) expression in system 2020 Nov Programmed death ligand (PD-L) 2 and PD-L1 are the second and first ligands, respectively, for programmed cell death-1 protein (PD-1), which is one of the key factors responsible for inhibitory T cell signaling, mediating mechanisms of tolerance and providing immune homeostasis. Studies have shown that PD-1 and its ligand PD-L1 are abnormally expressed in autoimmune diseases, such as rheumatoid arthritis and autoimmune hepatitis, but its other ligand, PD-L2, has rarely been studied. This study analyzed the changes in membrane-bound PD-L2 expression in peripheral blood mononuclear cells and soluble PD-L2 (sPD-L2) levels in the serum of patients with systemic lupus erythematosus (SLE) to explore the relationship between PD-L2 expression with disease activity and related test parameters. Our results showed that membrane-bound PD-L2 expression on monocytes was significantly higher and the sPD-L2 levels were significantly lower in SLE patients than in healthy subjects. Patients with active SLE accompanied by lupus nephritis, joint pain, and clinical manifestations of oral ulcers had relatively low secretion of sPD-L2. In addition, this secretion level was significantly and positively correlated with complement components 3 and 4 (C3/C4). These results suggest that PD-L2 may be a promising biomarker associated with the pathogenesis of SLE.
32752048 Reliability, Factor Structure and Predictive Validity of the Widespread Pain Index and Sym 2020 Jul 31 Fibromyalgia syndrome (FMS) is a chronic condition of widespread pain. In 2010, the American College of Rheumatology (ACR) proposed new diagnostic criteria for FMS based on two scales: the Widespread Pain Index (WPI) and Symptoms Severity (SS) scale. This study evaluated the reliability, factor structure and predictive validity of WPI and SS. In total, 102 women with FMS and 68 women with rheumatoid arthritis (RA) completed the WPI, SS, McGill Pain Questionnaire, Trait Anxiety Inventory, Fatigue Severity Scale, Oviedo Quality of Sleep Questionnaire, and Beck Depression Inventory. Pain threshold and tolerance and a measure of central sensitization to pain were obtained by pressure algometry. Values on WPI and SS showed negative-skewed frequency distributions in FMS patients, with most of the observations concentrated at the upper end of the scale. Factor analysis did not reveal single-factor models for either scale; instead, the WPI was composed of nine pain-localization factors and the SS of four factors. The Cronbach's α (i.e., Internal consistency) was 0.34 for the WPI,0.83 for the SS and 0.82 for the combination of WPI and SS. Scores on both scales correlated positively with measures of clinical pain, fatigue, insomnia, depression, and anxiety but were unrelated to pain threshold and tolerance or central pain sensitization. The 2010 ACR criteria showed 100% sensitivity and 81% specificity in the discrimination between FMS and RA patients, where discrimination was better for WPI than SS. In conclusion, despite their limited reliability, both scales allow for highly accurate identification and differentiation of FMS patients. The inclusion of more painful areas in the WPI and of additional symptoms in the SS may reduce ceiling effects and improve the discrimination between patients differing in disease severity. In addition, the use of higher cut-off values on both scales may increase the diagnostic specificity in Spanish samples.
32677764 Association of MASP2 levels and MASP2 gene polymorphisms with systemic lupus erythematosus 2020 Sep Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disorder. MASP2 is a mediator that plays an important role in complement system. As dysregulation of the complement system has been demonstrated to correlate with SLE pathogenesis, the role of MASP2 in lupus has not been widely discussed. In the present study, serum levels of MASP2 were evaluated in 61 lupus patients and 98 healthy controls by training cohort, and then a validation cohort including 100 lupus, 100 rheumatoid arthritis, 100 osteoarthritis, 100 gout, 44 Sjogren's syndrome, 41 ankylosing spondylitis patients confirmed the findings. Receiver operating characteristic (ROC) curve analysis determined the discriminatory capacity for serum MASP2. PCR methods tested the association of MASP2 gene polymorphisms (rs7548659, rs17409276, rs2273346, rs1782455 and rs6695096) and SLE risk. Impact of polymorphism on MASP2 serum levels was evaluated as well. Results showed that serum levels of MASP2 were significantly higher in lupus patients and correlated with some clinical, laboratory characteristics in the training cohort, and were much higher as compared to that in different rheumatic diseases patients in the validation cohort. Serum MASP2 showed a good diagnostic ability for lupus. Genotype frequencies and allele frequency of polymorphisms rs7548659, rs2273346 were strongly related to SLE risk, and genotypes of rs17409276, rs1782455, rs76695096 were significantly correlated with lupus genetic susceptibility. Interestingly, patients carrying GA genotype of rs17409276, TT, TC genotype of rs6695096 showed higher levels of serum MASP2. The findings suggested that MASP2 may be a potential disease marker for lupus, and correlate with SLE pathogenesis.
32443893 Inflammatory Skin-Derived Cytokines Accelerate Osteoporosis in Mice with Persistent Skin I 2020 May 20 Secondary osteoporosis can also be caused by chronic inflammatory skin disease as well as rheumatoid arthritis or inflammatory bowel disease. However, the exact role of osteoporosis in inflammatory skin conditions has not been elucidated. Using a mouse model of dermatitis, we investigated the pathophysiology of osteoporosis in inflammatory skin conditions and the therapeutic impact of osteoporosis medication on inflammatory skin disease. We employed model mice of spontaneous skin inflammation, specifically overexpressing human caspase-1 in the epidermis. Bone density and the expression of various mRNAs in the femur were examined by micro CT and RT-PCR. The effects of minodronate and anti-RANKL antibody on bone structure, histology, and femur blood flow were studied. The mouse model of skin inflammation showed a marked decrease in bone density compared to wild-type littermates with abnormalities in both bone resorption and formation. Minodronate improved bone density by decreasing osteoclasts, but anti-RANKL antibody did not improve. In the dermatitis model, the blood flow in the bone marrow was decreased, and minodronate restored this parameter. A model of persistent dermatitis exhibited marked osteoporosis, but the impact of chronic dermatitis on osteoporosis has not been thoroughly investigated. We should explore the pathogenesis of osteoporosis in skin inflammatory diseases.
32284921 Prevalence and Pattern of Pulmonary Manifestation in Patients with Connective Tissue Disor 2020 Apr 10 Background A substantial number of deaths and morbidities are caused by pulmonary involvement in connective tissue disorders (CTDs). The majority of patients suffering from CTDs show diverse clinical presentations arising in the lungs, the diaphragm, vasculature, and the pleura during the course of their disease. The clinical course is highly variable ranging from asymptomatic to symptomatic and from reversible to an irreversible stage. The most common occurring pulmonary appearance is the interstitial disease of the lung. In our study, we aim to determine the prevalence and pattern of pulmonary manifestation in patients with CTD presenting at a tertiary care hospital of Karachi, Pakistan. Methods A descriptive cross-sectional study was conducted in the department of Rheumatology Medical Unit II, Jinnah Postgraduate Medical Centre (JPMC), Karachi, Pakistan. All patients having CTD were enrolled. Patients with human immunodeficiency virus (HIV) infection, smokers, chronic obstructive pulmonary disease (COPD), bronchogenic carcinoma and patients with underlying cardiac disease were excluded from the study. Pulmonary manifestations like nonspecific interstitial pneumonia (NSIP), pleural effusion, usual interstitial pneumonia (UIP), interstitial pneumonitis, pulmonary arterial hypertension (PAH), tuberculosis, and pulmonary embolism were observed. In addition to this, treatment history and immunological test findings of these patients were also recorded. Results A total of 290 patients with rheumatologic disorders were included in this study, out of which 90.7% (263) were females and the average age of the entire cohort was 35.13 ± 12.53 years. A majority, 71% (206), of the patients were young (≤ 40 years of age). Rheumatoid arthritis (RA) was the most commonly observed rheumatologic disorder in this cohort which was in 70.3% (204) patients. RA was more prevalent in patients above 40 years of age as compared to young patients (≤ 40 years of age) with a frequency of 81% vs. 66%; p=0.012. Pulmonary involvement was observed in 27.2% of the patients while no pulmonary involvement was noted in 72.8% of patients. Conclusion Pulmonary manifestations in patients with CTD is not that uncommon (27.2%). PAH and NSIP collectively account for three-fourth of the total prevalent cases of pulmonary involvement in CTD patients.
32248717 Cholinergic agonists inhibit proliferation of human fibroblast-like synoviocytes and monoc 2020 Jun Background and purpose: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint destruction. Excessive proliferation of fibroblast-like synoviocytes (FLS) and over-expression of angiogenic factors play a crucial role in pannus formation and joint destruction in RA. Clarification of the role of cholinergic agonists in modulation of inflammation and immune system reactions is progressively ongoing. In this study, the anti-angiogenic effect of two cholinergic agonists, nicotine and ARR17779, on human FLS, and monocytic cell lines (U937) was evaluated.Experimental approach: The cells were cultured in DMEM supplemented with 10% FBS and treated with different doses of nicotine and ARR17779 in the presence of TNF-α, LPS, and IFN-γ. After 48 h, cell number was counted in different groups. After RNA extraction, cDNA was synthesized and the expression of VEGF and MMPs has been evaluated by real-time PCR using specific primers and probes. VEGF was assayed in U937 cell line supernatant using ELISA method.Key results: Both nicotine and ARR17779 inhibited FLS and U937 cell proliferation. Cholinergic agonists reduced the expression of MMPs and VEGF. VEGF level in supernatant of U937 cells treated with cholinergic agonists was also reduced.Conclusion and implications: Our results suggest that cholinergic agonists can modulate pathological conditions related to pannus formation in in-vitro conditions. Based on these results, cholinergic agonists can be considered as novel therapeutic options in RA. Further animal studies are needed before introducing these agents into clinical uses.
32301850 Occipital Plate Fixation in the Pediatric Population. 2020 Oct BACKGROUND: Occipital plate fixation has been shown to improve outcomes in cervical spine fusion. There is a paucity of literature describing occipital plate fixation, especially in the pediatric population. The authors reviewed a case series of 34 patients at a pediatric hospital who underwent cervical spine fusion with occipital plate fixation between 2003 and 2016. This study describes how occipital plates aid the cervical spine union in a case series of diverse, complex pediatric patients. METHODS: Our orthopaedic database at our institution was queried for patients undergoing an instrumented cervical spine procedure between 2003 and 2016. Medical records were used to collect diagnoses, fusion levels, surgical technique, and length of hospitalization, neurophysiological monitoring, complications, and revision procedures. RESULTS: Thirty-four patients met the inclusion criteria. The mean age was 10.9 years (range, 3-21 y). Indications for surgery included cervical instability, basilar invagination, and os odontoideum. These indications were often secondary to a variety of diagnoses, including trisomy 21, Klippel-Feil syndrome, and rheumatoid arthritis. The mean length of hospitalization was 10 days (range, 2 to 80 d). There were no cases of intraoperative dural leak, venous sinus bleeding from occipital screw placement, or implant-related complications. Postoperative complications included 2 cases of nonunion. Eight patients (24%) had follow-up surgery, only 3 (9%) of which were instrumentation revisions. Both patients with nonunion had repeat occipitocervical fixation procedures and achieved union with revision. CONCLUSIONS: Occipital plate fixation was successful for pediatric cervical spine fusion in this diverse cohort. The only procedure-related complication demonstrated was delayed union or nonunion and implant loosening (4/34, 12%) and there were no plate-related complications. This novel case series shows that occipital plate fixation is safe and effective for pediatric patients with complex diagnoses. LEVEL OF EVIDENCE: Level IV-case series.
32240781 Neurodegenerative diseases and Withania somnifera (L.): An update. 2020 Jun 28 ETHNOPHARMACOLOGICAL RELEVANCE: Withania somnifera (L.) Dunal also known as 'Ashwaghanda' in Sanskrit and as 'Indian Winter Cherry' in english. is an important medicinal herb in India. It is widely used in Indian systems of medicine as an adaptogen, nerve tonic, anti-stress, memory enhancer and against cognitive deficits, insomnia, anxiety, infectious diseases, infertility, rheumatoid arthritis and gout over thousands of years. Its formulations are mainly used in Unani and Ayurvedic system of medicine. It is a remarkable centuries old herbal Rasayana used to treat neuronal ailments and is known as ''Sattvic Kapha Rasayana. AIM OF THE STUDY: To review neuroprotective properties of Withania somnifera (L.)extract as well as its active constituents in neurodegenerative diseases and other neurological ailments. MATERIALS AND METHODS: The sources of information used in present article include Indian system of Medicine reports on the use of natural products, Medicinal books, research articles and scientific databases like PubMed, Google Scholar, Web of Science, Science-Direct, SciFinder, ACS Publications and Wiley Online Library. RESULTS: Research reports based largely on preclinical studies as well as few clinical trials have highlighted the neuroprotective role of Ashwagandha against many neurodegenerative diseases including Alzheimer's, Huntington's and Parkinson's disease. The protective effects of Ashwagandha were accomplished by restoring mitochondrial and endothelial function, mitigation of apoptosis, inflammation and oxidative stress mechanisms. CONCLUSION: In this review, we recapitulated neuroprotective properties of Ashwagandha extracts and/or its major constituents and discussed their mechanisms of action and potential therapeutic applications. The pre-clinical as well as clinical studies suggest the use of Withania somnifera (L.) against neurodegenerative disease. However, extensive studies are warranted to validate the use of extract or its single constituents for its clinical use.
32194903 Y-320, a novel immune-modulator, sensitizes multidrug-resistant tumors to chemotherapy. 2020 Y-320, a novel immune-modulator, inhibits IL-17 production by CD4(+) T cells stimulated with IL-15. Its use in autoimmune diseases such as rheumatoid arthritis has been documented. However, no studies have be conducted to evaluate its application in cancer treatment either as mono or combined therapy. This study demonstrated that while Y-320 had little effect on multidrug resistance (MDR) cell lines, it induced remarkable injury to MDR tumor cells when concurrently administered with other chemotherapeutic agents. Concomitant use of Y-320 with a low dose of paclitaxel significantly sensitized MDR tumors by inducing G2/M phase arrest and apoptosis. Further analyses indicated that Y-320 was a substrate of P-glycoprotein (P-gp). It could inhibit P-gp efflux function without altering P-gp expression, and subsequently reverse P-gp mediated drug resistance in MDR cells. The co-administration of Y-320 and paclitaxel suppressed tumor growth remarkably with an inhibition rate of 77.1% compared to 6.5% in the paclitaxel monotherapy group in vivo. This co-treatment did not increase extra complications in MDR tumor xenograft models. Particularly, no significant changes in body weight and hepatorenal serology were observed with the co-treatment. In conclusion, our results confirm that Y-320 is a promising chemotherapy sensitizer for the first time. The co-administration of Y-320 and chemotherapeutic agents might be an effective and low-toxicity chemotherapeutic regime for the MDR tumor patients.
32087087 Global miRNA and mRNA expression profiles identify miRNA-26a-2-3p-dependent repression of 2020 Jul Dysregulation in type I IFN and IFN-stimulated genes (ISGs) induced by monocytes is one of the key features of systemic sclerosis (SSc) pathogenesis. Abnormalities in microRNA (miRNA) expression are related to excessive IFN production, however the role of miRNA remains largely elusive in SSc monocytes. This study explores global miRNA-mRNA profiling of SSc monocytes and functional attenuation of IFN and ISGs by specific miRNAs. Global sequencing of mRNA (mRNA-seq) and miRNA (miRNA-seq) samples were performed simultaneously on healthy controls and SSc monocytes. Following computational analysis, selected miRNAs-mRNA candidates were validated, correlated with clinical parameters, and tested by functional assays. Transcriptomics data and qPCR analysis confirmed IFN signature in SSc but not in rheumatoid arthritis monocytes. Based on miRNA-seq analysis, five miRNAs were selected for further validation. Only the expression patterns of miRNA-26a-2-3p and miRNA-485-3p were confirmed and negatively correlated with clinical parameters. Exogenous delivery of miRNA-26a-2-3p to TLR-stimulated monocytic THP-1 cells specifically inhibited ISGs but not inflammasome activity in functional assays. In conclusion, our miRNA-mRNA co-sequencing and functional analysis identify miRNA-26a-2-3p as a new candidate, which is predicated to negatively regulate ISGs. This implies that reduced expression of miRNA-26a-2-3 may be involved in pathogenic IFN signature in SSc monocytes.
32074468 Microvascular Disease and Small-Vessel Disease: The Nexus of Multiple Diseases of Women. 2020 Jun Microvascular disease, or small-vessel disease, is a multisystem disorder with a common pathophysiological basis that differentially affects various organs in some patients. The prevalence of small-vessel disease in the heart has been found to be higher in women compared with men. Additionally, other diseases prominently affecting women, including heart failure with preserved ejection fraction, Takotsubo cardiomyopathy, cerebral small-vessel disease, preeclampsia, pulmonary arterial hypertension (PAH), endothelial dysfunction in diabetes, diabetic cardiomyopathy, rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, may have a common etiologic linkage related to microvascular disease. To the best of our knowledge this is the first article to investigate this potential linkage. We sought to identify various diseases with a shared pathophysiology involving microvascular/endothelial dysfunction that primarily affect women, and their potential implications for disease management. Advanced imaging technologies, such as magnetic resonance imaging and positron-emission tomography, enable the detection and increased understanding of microvascular dysfunction in various diseases. Therapies that improve endothelial function, such as those used in PAH, may also be associated with benefits across the full spectrum of microvascular dysfunction. A shared pathology across multiple organ systems highlights the need for a collaborative, multidisciplinary approach among medical subspecialty practitioners who care for women with small-vessel disease. Such an approach may lead to accelerated research in diseases that affect women and their quality of life.
31680207 Biologic therapy in the idiopathic inflammatory myopathies. 2020 Feb The idiopathic inflammatory myopathies (IIM) are a group of autoimmune diseases resulting from inflammation of muscle and manifesting as weakness, though a range of extra-muscular manifestations are observed. These are often correlated closely with disease subtype and the presence of myositis-specific/myositis-associated antibodies. IIM are notoriously difficult to treat and often refractory to glucocorticoid therapy and synthetic immunosuppressants. Both the innate and adaptive immune systems are implicated in the pathogenesis of IIM. A growing understanding of the key cytokines as well as the cell-mediated and antibody effectors of disease has identified multiple potential targets for biologic therapy. The most widely used of these is B-cell depletion via rituximab though the tumour necrosis factor inhibitors and other biologic therapies used in diseases such as rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis have also been trialled. This review summarises the literature thus far on biologic therapy in IIM, highlighting both the significant trials that influence current treatment regimens and also the continuing need for further research to inform more effective therapies.
31615316 Should isoniazid prophylaxis be prescribed to the patients under tumor necrosis factor-alp 2020 Dec INTRODUCTION: The aim of this study was to present the follow-up results of 110 patients who were given anti-tumor necrosis factor alpha (TNF-α) therapy for rheumatic and dermatologic diseases in a country with a high rates of active and latent tuberculosis bacillus infection. MATERIAL AND METHODS: Between February 2008 and January 2015, 110 cases in the age range of 23-77 who are using anti-TNF-α were included in the study retro-prospectively. RESULTS: 52.7% of them (n = 58) were male. The most common diagnoses were rheumatoid arthritis (42.7%) and ankylosing spondylitis (38.2%). Most frequently given treatment were infliximab 37.3% and etanercept 30.9%, respectively. The 65 patients whose first tuberculin skin test (TST) value "5 mm and above" was started daily 300 mg INH prophylaxis for 9 months but 3 patients had not been started because of refusing treatment. In only one case chemoprophylaxis has had to be interrupted because of high liver function test due to the INH prophylaxis. TST conversion was observed in 14 patients. Further follow-up, it was observed that 4 patients had TST's positivity. Isoniazide (INH) prophylaxis was started these 18 patients (42.9%). Although INH prophylaxis has been given in two patients, they developed active tuberculosis in follow-up. CONCLUSION: Considering the INH resistance in our country, all patients especially the ones with residual lesion and history of previous exposure, should be followed up closely during the anti-TNF-α treatment.
31955068 Alleviating effect of paeoniflorin-6'-O-benzene sulfonate in antigen-induced experimental 2020 Mar Primary Sjögren's syndrome (pSS) is an autoimmune disease of unresolved aetiology that affects the exocrine glands. Clinical symptoms frequently also involve skin, liver, kidney and neurovascular components. The pathogenesis of pSS is still unclear but B cell hyperactivity has been identified as a hallmark of pSS. Currently, a curative therapeutic agent is lacking. In this study, we explored whether paeoniflorin-6'-O-benzene (CP-25) exerted therapeutic effects through regulating B lymphocyte migration via CXCR5-GRK2-MAPK mediated signaling pathways in a mouse model of antigen-induced, experimental Sjögren's syndrome (ESS). We found that CP-25 increased the salivary flow and alleviated the histopathology of ESS. Furthermore, CP-25 reduced the viability of B lymphocyte and limited the target organs index. In the peripheral blood and salivary gland of ESS mice, CP-25 down-regulated the proportion of total B cells, CXCR5+ B cells and PDCA1 + CD19- and limited the presence of phosphorylated (p-) p38 and ERK (p-ERK). Besides, CP-25 increased the percentage of memory B cells in the peripheral blood and reduced it in salivary gland. Furthermore, in vitro, CP-25 down-regulated p-p38, p-ERK, CXCR5 and membrane GRK2, and increased cytoplasm GRK2 in Maver-1 cells, a mantle cell lymphoma cell line, causing a lower migration ability of Maver-1 cells. Thus, we define CP-25 as a novel compound that is a potent therapeutic agent for pSS which modulates B lymphocyte subsets and impacts the migration of B lymphocytes through regulating the CXCR5-GRK2-ERK/p38 signaling pathway.
32586320 Alterations in the chondrocyte surfaceome in response to pro-inflammatory cytokines. 2020 Jun 26 BACKGROUND: Chondrocytes are exposed to an inflammatory micro-environment in the extracellular matrix (ECM) of articular cartilage in joint diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA). In OA, degenerative changes and low-grade inflammation within the joint transform the behaviour and metabolism of chondrocytes, disturb the balance between ECM synthesis and degradation, and alter the osmolality and ionic composition of the micro-environment. We hypothesize that chondrocytes adjust their physiology to the inflammatory microenvironment by modulating the expression of cell surface proteins, collectively referred to as the 'surfaceome'. Therefore, the aim of this study was to characterize the surfaceome of primary equine chondrocytes isolated from healthy joints following exposure to the pro-inflammatory cytokines interleukin-1-beta (IL-1β) and tumour necrosis factor-alpha (TNF-α). We employed combined methodology that we recently developed for investigating the surfaceome in stem cells. Membrane proteins were isolated using an aminooxy-biotinylation technique and analysed by mass spectrometry using high throughput shotgun proteomics. Selected proteins were validated by western blotting. RESULTS: Amongst the 431 unique cell surface proteins identified, a high percentage of low-abundance proteins, such as ion channels, receptors and transporter molecules were detected. Data are available via ProteomeXchange with identifier PXD014773. A high number of proteins exhibited different expression patterns following chondrocyte stimulation with pro-inflammatory cytokines. Low density lipoprotein related protein 1 (LPR-1), thrombospondin-1 (TSP-1), voltage dependent anion channel (VDAC) 1-2 and annexin A1 were considered to be of special interest and were analysed further by western blotting. CONCLUSIONS: Our results provide, for the first time, a repository for proteomic data on differentially expressed low-abundance membrane proteins on the surface of chondrocytes in response to pro-inflammatory stimuli.
30863888 Assessing acrolein for determination of the severity of brain stroke, dementia, renal fail 2020 Feb It was found recently that acrolein (CH(2)=CH-CHO), mainly produced from spermine, is more toxic than ROS (reactive oxygen species, O(2)(-·), H(2)O(2), and ·OH). In this review, we describe how the seriousness of brain infarction, dementia, renal failure, and Sjӧgren's syndrome is correlated with acrolein. In brain infarction and dementia, it was possible to identify incipient patients with high sensitivity and specificity by measuring protein-conjugated acrolein (PC-Acro) in plasma together with IL-6 and CRP in brain infarction and Aβ(40/42) in dementia. The level of PC-Acro in plasma and saliva correlated with the seriousness of renal failure and Sjӧgren's syndrome, respectively. Thus, development of acrolein scavenger medicines containing SH-group such as N-acetylcysteine derivatives is important to maintain QOL (quality of life) of the elderly.
32503658 Prevalence of co-existing autoimmune disease in juvenile idiopathic arthritis: a cross-sec 2020 Jun 5 BACKGROUND: Many autoimmune diseases share common pathogenic mechanisms, cytokine pathways and systemic inflammatory cascades; however, large studies quantifying the co-existence of autoimmune diseases in patients with juvenile idiopathic arthritis (JIA) have not been conducted. METHODS: We performed a cross-sectional study using two United States administrative healthcare claims databases (Truven Health MarketScan® Commercial Database and IMS PharMetrics database) to screen for the prevalence of multiple autoimmune diseases in patients with JIA and in a control group with attention deficit hyperactivity disorder (ADHD). Patients with a diagnosis code for JIA or ADHD between January 1, 2006 and September 30, 2017 were separated into two age cohorts (< 18 and ≥ 18 years) and matched (maximum 1:5) based on age, sex, number of medical encounters, and calendar year of diagnosis. The prevalence rates of 30 pre-specified autoimmune diseases during the 12-month periods before and after diagnosis were compared. RESULTS: Overall, 29,215 patients with JIA and 134,625 matched control patients with ADHD were evaluated. Among patients in the MarketScan database, 28/30 autoimmune diseases were more prevalent in patients with JIA aged < 18 years and 29/30 were more prevalent in patients aged ≥ 18 years when compared with a matched cohort of patients with ADHD. In the PharMetrics database, 29/30 and 30/30 autoimmune diseases were more prevalent in patients with JIA aged < 18 and ≥ 18 years, respectively, compared with a matched cohort of patients with ADHD. Among patients with JIA aged < 18 years, the greatest odds ratios (ORs) were seen for Sjögren's syndrome/sicca syndrome and uveitis. Among patients aged ≥ 18 years in the MarketScan database, the greatest ORs were recorded for uveitis. Data from the PharMetrics database indicated that the greatest ORs were for uveitis and chronic glomerulonephritis. CONCLUSIONS: Patients with JIA are more likely to have concurrent autoimmune diseases than matched patients with ADHD. Having an awareness of the co-existence of autoimmune diseases among patients with JIA may play an important role in patient management, treatment decisions, and outcomes. TRIAL REGISTRATION: Not applicable.
32277856 Sex-mediated elevation of the specialized pro-resolving lipid mediator levels in a Sjögre 2020 Jun Our previous results showed that the specialized pro-resolving mediator (SPM) Resolvin D1 (RvD1) promotes resolution of inflammation in salivary glands in non-obese diabetic (NOD)/ShiLtJ, a mouse model for Sjögren's syndrome (SS). Additionally, mice lacking the RvD1 receptor ALX/FPR2 show defective innate and adaptive immune responses in salivary glands. Particularly, ALX/FPR2 KO mice exhibit exacerbated inflammation in their salivary glands in response to systemic LPS treatment. Moreover, female ALX/FPR2 KO mice show increased autoantibody production and loss of salivary gland function with age. Together, these studies suggest that an underlying SPM dysregulation could be contributing to SS progression. Therefore, we investigated whether SPM production is altered in NOD/ShiLtJ using metabololipidomics and enzyme-linked immunosorbent assay (ELISA). Our results demonstrate that SPM levels were broadly elevated in plasma collected from NOD/ShiLtJ female mice after disease onset, whereas these drastic changes did not occur in male mice. Moreover, gene expression of enzymes involved in SPM biosynthesis were altered in submandibular glands (SMG) from NOD/ShiLtJ female mice after disease onset, with 5-LOX and 12/15-LOX being downregulated and upregulated, respectively. Despite this dysregulation, the abundances of the SPM products of these enzymes (ie, RvD1 and RvD2) were unaltered in freshly isolated SMG cells suggesting that other cell populations (eg, lymphocytes) may be responsible for the overabundance of SPMs that we observed. The elevation of SPMs noted here appeared to be sex mediated, meaning that it was observed only in one sex (females). Given that SS primarily affects females (roughly 90% of diagnosed cases), these results may provide some insights into the mechanisms underlying the observed sexual dimorphism.
31642912 The quantitative assessment of interstitial lung disease with positron emission tomography 2020 Jun 1 OBJECTIVES: The reversibility of interstitial lung disease (ILD) in SSc is difficult to assess by current diagnostic modalities and there is clinical need for imaging techniques that allow for treatment stratification and monitoring. 18F-Fluorodeoxyglucose (FDG) PET/CT scanning may be of interest for this purpose by detection of metabolic activity in lung tissue. This study aimed to investigate the potential role of 18F-FDG PET/CT scanning for the quantitative assessment of SSc-related active ILD. METHODS: 18F-FDG PET/CT scans and high resolution CT scans of eight SSc patients, including five with ILD, were analysed. For comparison, reference groups were included: eight SLE patients and four primary Sjögren's syndrome (pSS) patients, all without ILD. A total of 22 regions of interest were drawn in each patient at apical, medial and dorsobasal lung levels. 18F-FDG uptake was measured as mean standardized uptake value (SUVmean) in each region of interest. Subsequently, basal/apical (B/A) and medial/apical (M/A) ratios were calculated at patient level (B/A-p and M/A-p) and at tissue level (B/A-t and M/A-t). RESULTS: SUVmean values in dorsobasal ROIs and B/A-p ratios were increased in SSc with ILD compared with SSc without ILD (P = 0.04 and P = 0.07, respectively), SLE (P = 0.003 and P = 0.002, respectively) and pSS (P = 0.03 and P = 0.02, respectively). Increased uptake in the dorsobasal lungs and increased B/A-t ratios corresponded to both ground glass and reticulation on high resolution CT. CONCLUSION: Semi-quantitative assessment of 18F-FDG PET/CT is able to distinguish ILD from non-affected lung tissue in SSc, suggesting that it may be used as a new biomarker for SSc-ILD disease activity.
33162932 Unusual Presentation of Polyautoimmunity and Renal Tubular Acidosis in an Adolescent With 2020 Background: Hashimoto's thyroiditis is frequently associated with other autoimmune diseases and may include renal involvement. Case description: A 17-year-old female with previously diagnosed Hashimoto's thyroiditis and vitiligo was admitted to a pediatric intensive care unit with hypokalemic paralysis and acidosis, after having suffered from recurrent muscular weakness for approximately one year. A few days later she developed central pontine myelinolysis. After initial stabilization she was also diagnosed with distal renal tubular acidosis (dRTA) and tubular proteinuria which can occur in Sjögren's syndrome. Extended screening for autoimmune diseases additionally revealed celiac disease. Treatment with Prednisone and substitution of potassium quickly lead to the resolution of proteinuria and dRTA, but unilateral paralysis of the sixth nerve as a result of central pontine myelinolysis was irreversible. Conclusions: This is the rare case of polyautoimmunity including autoimmune thyroiditis, Sjögren's syndrome, vitiligo and celiac disease in an adolescent with few disease-specific symptoms. The diagnoses were made via a complicating nephritis causing dRTA and proteinuria. Delay in diagnosis lead to permanent neurological damage. This case highlights the need for pediatricians to be aware of rare accompanying diseases and their complications in "common" pediatric autoimmune diseases like Hashimoto's thyroiditis and celiac disease.