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ID PMID Title PublicationDate abstract
29138598 Familial aggregation of myasthenia gravis in affected families: a population-based study. 2017 INTRODUCTION: Myasthenia gravis (MG) is clinically heterogeneous and can be life-threatening if bulbar or respiratory muscles are involved. However, relative contributions of genetic, shared, and nonshared environmental factors to MG susceptibility remain unclear. The aim of this study was to examine the familial aggregation and heritability of MG and the relative risks (RRs) of other autoimmune diseases in the relatives of patients with MG. METHODS: A population-based family study using the Taiwan National Health Insurance (NHI) Database was conducted. Participants included all individuals (N=23,422,955) who were actively registered in the NHI Database in 2013, 15,066 of whom had at least one first-degree relative with MG. We identified 8,638 parent-child relationships, 3,279 with an affected offspring, 3,134 with affected siblings, and 26 with affected twins. Prevalence and RRs of MG and other autoimmune diseases in the relatives of patients as well as the relative contributions of heritability, shared, and nonshared environmental factors to MG susceptibility were measured. RESULTS: RRs (95% confidence intervals [CIs]) for MG were 17.85 (8.71-36.56) for patients' siblings, 5.33 (2.79-10.18) for parents, 5.82 (3.03-11.16) for offspring, and 1.42 (0.20-10.10) for spouses without genetic similarities. RRs (95% CIs) in individuals with a first-degree relative with MG were 2.18 (1.53-3.12) for systemic lupus erythematosus, 1.73 (1.09-2.74) for primary Sjögren's syndrome, 1.90 (1.66-2.18) for autoimmune thyroid disease, and 1.68 (1.22-2.30) for rheumatoid arthritis. Accountability for the phenotypic variance of MG was 82.1% for familial transmission and 17.9% for nonshared environmental factors. CONCLUSION: Individual risks of MG and other autoimmune diseases are increased in the relatives of patients with MG. Familial transmission of MG was estimated to be 82.1%.
29095837 Resveratrol downregulates inflammatory pathway activated by lymphotoxin α (TNF-β) in art 2017 While Lymphotoxin α (TNF-β), a product of lymphocytes, is known to play a pivotal role in inflammatory joint environment, resveratrol has been shown to possess anti-inflammatory and chondroprotective effects via activation of the histondeacetylase Sirt1. Whether TNF-β induction of inflammatory pathways in primary human chondrocytes (PCH) can be modulated by resveratrol, was investigated. Monolayer and alginate cultures of PCH were treated with TNF-β, anti-TNF-β, nicotinamide (NAM), antisense oligonucleotides against Sirt1 (Sirt1-ASO) and/or resveratrol and co-cultured with T-lymphocytes. We found that resveratrol suppressed, similar to anti-TNF-β, TNF-β-induced increased adhesiveness in an inflammatory microenvironment of T-lymphocytes and PCH. In contrast, knockdown of Sirt1 by mRNA abolished the inhibitory effects of resveratrol on the TNF-β-induced adhesiveness, suggesting the essential role of this enzyme for resveratrol-mediated anti-inflammatory signaling. Similar results were obtained in PCH stimulated with TNF-α. Sirt1-ASO, NAM or TNF-β, similar to T-lymphocytes induced inflammatory microenvironment by down-regulation of cartilage-specific proteins, Sox9, Ki67 and enhanced NF-κB-regulated gene products involved in inflammatory and degradative processes in cartilage (MMP-9/-13, COX-2, caspase-3), NF-κB activation and its translocation to the nucleus. Moreover, resveratrol reversed the TNF-β-, NAM-, T-lymphocytes-induced up-regulation of various NF-κB-regulated gene products. Down-regulation of Sirt1 by mRNA interference abrogated the effect of resveratrol on TNF-β-induced effects. Ultrastructural and cell viability assay investigations revealed that resveratrol revoked TNF-β-induced dose-dependent degradative/apoptotic morphological changes, cell viability and proliferation in PCH. Taken together, suppression of TNF-β-induced inflammatory microenvironment in PCH by resveratrol/Sirt1 might be a novel therapeutic approach for targeting inflammation during rheumatoid arthritis.
29075476 Phylogeographic and phylogenetic analysis for Tripterygium species delimitation. 2017 Oct Tripterygium wilfordii (Celastraceae) is a traditional Chinese medicine; and the dried root and rhizome constitute the main officinal parts. Tripterygium wilfordii has been identified as a potential candidate for the treatment of systemic lupus erythematosus, rheumatoid arthritis, nephritis, asthma, leprosy, and cancer. The phylogenetic relationships within the Tripterygium genus are ambiguous; thus, our aim is to clarify the relationships within this genus using phylogeographic and phylogenetic analyses. Here, we first sequenced three plastid DNA regions (i.e., psbA-trnH, rpl32-trnL, and trnL-trnF) and found that Tripterygium hypoglaucum and T. wilfordii were clustered together based on the strength of the topology in the phylogenetic analysis: T. hypoglaucum is polyphyletic, and T. wilfordii is paraphyletic. A spatial analysis of molecular variance showed that the best group value is 4, and the groups were almost consistent with the topology of in the phylogenetic analysis. The Mantel analyses of Tripterygium using IBD web showed statistically significant relationships between genetic and geographical distance distributions (r = .3479, p < .0001). The molecular dating using Fossil calibration indicated that the divergence in Tripterygium was approximately 8.13 Ma. Furthermore, we also analyzed four DNA regions (i.e., ITS2, psbA-trnH, matK, and rbcL) that were obtained from the NCBI nucleotide database; these results showed that T. wilfordii and T. hypoglaucum clustered together, while Tripterygium regelii represented a separate cluster. Tripterygium hypoglaucum and T. wilfordii were never distinct lineages, and the species circumscriptions are artificial. We propose that T. wilfordii and T. hypoglaucum are conspecific, while T. regelii likely constitutes a separate species.
29071567 Novel anti-adipogenic activity of anti-malarial amodiaquine through suppression of PPARγ 2017 Nov Amodiaquine (AQ) was developed as a selective drug against Plasmodium falciparum malaria infection and has received increasing attention as a therapeutic agent for the treatment of rheumatoid arthritis, Parkinson's disease, and cancer due to its anti-inflammatory, anti-proliferative, and autophagic-lysosomal blockade properties. As autophagy activation is involved in promoting adipogenic differentiation, we examined whether anti-autophagic AQ affected adipocyte differentiation of 3T3-L1 pre-adipocytes. AQ dose-dependently and significantly suppressed adipocyte differentiation in conjunction with decreases in lipid droplet formation and expression of adipogenic markers including adiponectin, adipocyte fatty acid-binding protein 2 (aP2), resistin, and leptin. Although peroxisome proliferator-activated receptor γ (PPARγ) decreases by inhibition of autophagy, AQ treatment did not induce PPARγ degradation despite the suppression of autophagolysosomal degradation. Instead, AQ suppressed the PPARγ activity to transcriptionally activate the aP2 gene transcription through the selective prevention of nuclear localization of PPARγ. These results demonstrated the novel anti-adipogenic activity of AQ and identified its underlying mechanism that AQ suppressed adipogenic gene expression and lipid formation by inhibiting nuclear localization of PPARγ in an autophagy-independent manner. AQ is recommended as a safe and effective anti-obesity drug for controlling overweight and obesity.
28708108 Gut-CNS-Axis as Possibility to Modulate Inflammatory Disease Activity-Implications for Mul 2017 Jul 14 In the last decade the role of environmental factors as modulators of disease activity and progression has received increasing attention. In contrast to classical environmental modulators such as exposure to sun-light or fine dust pollution, nutrition is an ideal tool for a personalized human intervention. Various studies demonstrate a key role of dietary factors in autoimmune diseases including Inflammatory Bowel Disease (IBD), rheumatoid arthritis or inflammatory central nervous system (CNS) diseases such as Multiple Sclerosis (MS). In this review we discuss the connection between diet and inflammatory processes via the gut-CNS-axis. This axis describes a bi-directional communication system and comprises neuronal signaling, neuroendocrine pathways and modulation of immune responses. Therefore, the gut-CNS-axis represents an emerging target to modify CNS inflammatory activity ultimately opening new avenues for complementary and adjunctive treatment of autoimmune diseases such as MS.
28698231 Survival benefit of statin use in ankylosing spondylitis: a general population-based cohor 2017 Oct OBJECTIVES: Recent studies have shown an increase in both cardiovascular and all-cause mortality in ankylosing spondylitis (AS). We examined the potential survival benefit of statin use in AS within a general population context. METHODS: We performed an incident user cohort study with time-stratified propensity score matching using a UK general population database between 1 January 2000 and 31 December 2014. To account for potential confounders, we compared propensity score-matched cohorts of statin initiators and non-initiators using 1-year cohort accrual blocks. The variables used to create the propensity score model included disease duration, body mass index, lifestyle factors, comorbidities and medication use. RESULTS: Using unmatched AS cohorts, statin initiators (n=1430) showed a 43% higher risk of mortality than non-initiators (n=1430) (HR=1.43; 95% CI 1.12 to 1.84). After propensity score matching, patients with AS who initiated statins (n=1108) had 96 deaths, and matched non-initiators (n=1108) had 134 deaths over a mean follow-up of 5.3 and 5.1 years, respectively. This corresponded to mortality rates of 16.5 and 23.8 per 1000 person-years (PY), respectively, resulting in an HR of 0.63 (95% CI 0.46 to 0.85) and an absolute mortality rate difference of 7.3 deaths per 1000 PY (95% CI 2.1 to 12.5). CONCLUSION: This general population-based cohort study suggests that statin initiation is associated with a substantially lower risk of mortality among patients with AS. The magnitude of the inverse association appears to be larger than that observed in randomised trials of the general population and in population-based cohort studies of patients with rheumatoid arthritis.
28666651 Restrictions of cervical flexion after laminoplasty increase in the mechanical stress at t 2017 Nov Increased range of motion (ROM) at O-C2 after cervical laminoplasty is thought to be a compensatory change due to loss of cervical ROM after surgery. Retro-odontoid pseudotumor in non-RA patients is also caused by loss of ROM at C2-C7 causing mechanical stress on upper cervical spine. The aim of this study was to measure the occipitocervical alignment before and after cervical laminoplasty, and examine the factors associated with postoperative retro-odontoid soft tissue (ROST) enlargement. The study comprised 72 non-RA patients (51 males and 21 females, mean age 65.2years) who underwent cervical laminoplasty. The cervical angles (O-C1, O-C2, C1-C2, and C2-C7) were measured and ROST thickness was evaluated on mid-sagittal T1-weighted MRI before surgery and 2years after surgery. Correlations between radiographic changes and postoperative ROST enlargement were examined. The results shows that postoperative ROM and kyphotic angle in flexion position at O-C2 significantly increased, and postoperative ROM and kyphotic angle in flexion position at C2-C7 significantly decreased compared with preoperative values. On stepwise multiple regression analysis, age (beta=0.273, p<0.01) and restriction of cervical flexion postoperatively (beta=0.235, p<0.01) were independently associated with ROST enlargement. In conclusion, occipitocervical ROM increased and C2-C7 ROM, especially C2-C7 kyphotic angle in flexion, reduced after cervical laminoplasty. The ROST enlargement was associated with reduction in cervical flexion. These results indicate that preservation of cervical ROM, especially kyphotic angle in flexion, after cervical laminoplasty contribute to reduction of mechanical stress at the occipitocervical junction.
28328217 Development of a Selective Inhibitor of Protein Arginine Deiminase 2. 2017 Apr 13 Protein arginine deiminase 2 (PAD2) plays a key role in the onset and progression of multiple sclerosis, rheumatoid arthritis, and breast cancer. To date, no PAD2-selective inhibitor has been developed. Such a compound will be critical for elucidating the biological roles of this isozyme and may ultimately be useful for treating specific diseases in which PAD2 activity is dysregulated. To achieve this goal, we synthesized a series of benzimidazole-based derivatives of Cl-amidine, hypothesizing that this scaffold would allow access to a series of PAD2-selective inhibitors with enhanced cellular efficacy. Herein, we demonstrate that substitutions at both the N-terminus and C-terminus of Cl-amidine result in >100-fold increases in PAD2 potency and selectivity (30a, 41a, and 49a) as well as cellular efficacy (30a). Notably, these compounds use the far less reactive fluoroacetamidine warhead. In total, we predict that 30a will be a critical tool for understanding cellular PAD2 function and sets the stage for treating diseases in which PAD2 activity is dysregulated.
27913752 Expression and bioactivity of human α-fetoprotein in a Bac-to-Bac system. 2017 Feb 28 α-fetoprotein (AFP) is an early serum growth factor in foetal embryonic development and hepatic oncogenesis. A growing number of investigations of AFP as a tumour-specific biomarker have concluded that AFP is an important target for cancer treatment. AFP also plays an immunomodulatory role in the treatment of several autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, myasthenia gravis and thyroiditis. In an effort to support biochemical screening and drug design and discovery, we attempted to express and purify human AFP in a Bac-to-Bac system. Two key factors affecting the expression of recombinant human AFP (R-AFP), namely the infectious baculovirus inoculum volume and the culturing time post-infection, were optimized to maximize the yield. We achieved a high yield of approximately 1.5 mg/l of harvested medium with a 72-96 h incubation period after infection and an inoculum volume ratio of 1:100. We also assessed the role of R-AFP in the proliferation of the human liver cancer cell line Bel 7402, and the results indicated that R-AFP promoted the growth of hepatoma cells. We concluded that this method can produce high yields of R-AFP, which can be used for studies related to AFP.
27813112 Developmental toxicity of auranofin in zebrafish embryos. 2017 May Auranofin (AF) is used in clinic for the treatment of rheumatoid arthritis, repurposing of AF as an anticancer drug has just finished a phase I/II clinical trial, but the developmental toxicity of AF remains obscure. This study focused on its developmental toxicity by using zebrafish embryos. Zebrafish embryos were exposed to different concentrations (1, 2.5, 5, 10 μm) of AF from 2 h post-fertilization (hpf) to 72 hpf. At 72 hpf, two major developmental defects caused by AF were found, namely severe pericardial edema and hypopigmentation, when embryos were exposed to concentrations higher than 2.5 μm. Biochemical detection of oxidative stress enzyme combined with expressions of a series of genes related to oxidative stress, cardiac, metal stress and pigment formation were subsequently tested. The superoxide dismutase activity was decreased while malondialdehyde content was accumulated by AF treatment. The expression of oxidative stress-related genes (sod1, gpx1a, gst), pigment-related genes (mitfb, trp-1a) and one metal stress-related gene ctr1 were all decreased by AF exposure. The expressions of cardiac-related genes (amhc, vmhc) and one metal-related gene hsp70 were found to be significantly upregulated by AF exposure. These findings indicated the potential developmental toxicity of AF on zebrafish early development. Copyright © 2016 John Wiley & Sons, Ltd.
27309544 The correlation between miR-200c and the severity of interstitial lung disease associated 2017 Mar OBJECTIVES: To explore the correlation between microRNA (miR)-200c and the severity of interstitial lung disease (ILD) associated with connective tissue diseases (CTDs). METHOD: We recruited 218 patients with CTDs who were evaluated with high-resolution computed tomography (HRCT) and the pulmonary function test (PFT). Peripheral blood mononuclear cells (PBMCs) were acquired from 23 patients with systemic sclerosis (SSc), 29 with dermatomyositis/polymyositis (DM/PM), 30 with primary Sjögren's syndrome (pSS), 47 with rheumatoid arthritis (RA), and 23 normal controls to detect the expression level of miR-200c by quantitative reverse transcription polymerase chain reaction (QRT-PCR). miR-200c levels were compared among the different disease groups, between the group with ILD (CTD+ILD) and the group without ILD (CTD-ILD), and between mild and severe ILD groups. Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were compared among the different CTD groups and the different CTD+ILD groups. RESULTS: The miR-200c level in the SSc group was significantly higher than in the DM/PM, pSS, and RA groups, and the levels in the DM/PM and pSS groups were significantly higher than in the RA group. The level of miR-200c in the CTD+ILD group was significantly higher than in the CTD-ILD group, and the level in the severe ILD group was significantly higher than in the mild ILD group. FVC and FEV1 were significantly different among the different CTD groups, and among the different CTD+ILD groups. There was a negative correlation between the level of miR-200c and FVC and FEV1. CONCLUSIONS: The level of miR-200c was positively correlated with the severity of ILD, and miR-200c in PBMCs could be a biomarker of the severity of ILD in CTDs.
28362980 Role of Th1/Th2 cytokines in the diagnosis and prognostic evaluation of ankylosing spondyl 2017 Mar 16 Ankylosing spondylitis (AS), a progressive disease of the spine, manifests as peripheral arthritis with tendon and ligament inflammation that restricts activity. AS is a rheumatoid autoimmune disease although the rheumatoid factor is absent in patients with AS. It is characterized by inflammatory changes such as elevated levels of serum inflammatory factors. The roles of Th1 and Th2 cytokines in autoimmune diseases are well known. However, the roles of these cytokines in the diagnosis and prognosis of AS is poorly understood. The aim of this study was to investigate the roles of Th1/Th2 cytokines in the diagnosis and prognosis of AS. The BASDAI activity, BASFI functional index, BASMI measurement score, and the levels of CRP and ESR were measured during the treatment of patients with active AS. The levels of IFN-γ and TNF-α (Th1 cytokines) and IL-4 and IL-10 (Th2 cytokines) were quantified. The levels of IL-4 and IL-10 were significantly low in the serum of patients with active AS, who also had high IFN-γ and TNF-α levels compared to those in the control individuals (P < 0.05). After treatment, the levels of IL-4 and IL-10 increased while those of IFN-γ and TNF-α decreased compared to those in individuals with active AS (P < 0.05). The disease activity index correlated positively with levels of IFN-γ and TNF-α and negatively with levels of IL-4 and IL-10, but not with that of CRP or ESR. Changes in the levels of Th1/2 cytokines in patients with AS may reflect disease activity and prognosis.
28369296 The Not-So-Good Prognosis of Streptococcal Periprosthetic Joint Infection Managed by Impla 2017 Jun 15 BACKGROUND. Streptococci are not an infrequent cause of periprosthetic joint infection (PJI). Management by debridement, antibiotics, and implant retention (DAIR) is thought to produce a good prognosis, but little is known about the real likelihood of success. METHODS. A retrospective, observational, multicenter, international study was performed during 2003-2012. Eligible patients had a streptococcal PJI that was managed with DAIR. The primary endpoint was failure, defined as death related to infection, relapse/persistence of infection, or the need for salvage therapy. RESULTS. Overall, 462 cases were included (median age 72 years, 50% men). The most frequent species was Streptococcus agalactiae (34%), and 52% of all cases were hematogenous. Antibiotic treatment was primarily using β-lactams, and 37% of patients received rifampin. Outcomes were evaluable in 444 patients: failure occurred in 187 (42.1%; 95% confidence interval, 37.5%-46.7%) after a median of 62 days from debridement; patients without failure were followed up for a median of 802 days. Independent predictors (hazard ratios) of failure were rheumatoid arthritis (2.36), late post-surgical infection (2.20), and bacteremia (1.69). Independent predictors of success were exchange of removable components (0.60), early use of rifampin (0.98 per day of treatment within the first 30 days), and long treatments (≥21 days) with β-lactams, either as monotherapy (0.48) or in combination with rifampin (0.34). CONCLUSIONS. This is the largest series to our knowledge of streptococcal PJI managed by DAIR, showing a worse prognosis than previously reported. The beneficial effects of exchanging the removable components and of β-lactams are confirmed and maybe also a potential benefit from adding rifampin.
28150184 Thrombotic thrombocytopenic purpura in a new onset lupus patient? 2017 Apr We are presenting a case of TTP with undetectable levels of ADAMTS 13 in a 39-year-old woman. Diagnosis of systemic lupus was evoked in the setting of thrombotic microangiopathy. The patient presented normal renal function but important neurological impairment. Treatment with daily plasmapheresis as well as Rituximab, cyclophosphamide as steroids was required to achieve clinical improvement.
28816552 The role of biopsy in lacrimal gland inflammation: A clinicopathologic study. 2017 Dec PURPOSE: To determine the causes of lacrimal gland inflammation based on histopathology and systemic evaluation. METHODS: This is a retrospective case series study. From the University of British Columbia Orbit Clinic between January 1976 and December 2008, we reviewed the medical records of 60 patients who presented with inflammatory features of the lacrimal gland (i.e., erythema, edema, or tenderness) in which the diagnoses were not possible clinically and on imaging alone. As was our routine practice, all these patients underwent lacrimal gland biopsy before starting any treatment. RESULTS: The histopathologic findings of the 60 patients showed that 37 (61.7%) had identifiable types of lacrimal inflammation including 10 with Sjogren's syndrome, seven with sarcoidal reaction, six with feature of granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis), five with lymphoma, two with sclerosing inflammation, two with IgG4-related dacryoadenitis, and one patient each with infectious dacryoadenitis, myoepithelial carcinoma, xanthogranuloma, eosinophilic angiocentric fibrosis, and eosinophilic allergic granulomatous nodule. The histopathologic findings of the remaining 23 (38.3%) patients showed nonspecific inflammation of the lacrimal gland. 23 patients (38.3%) had associated systemic diseases. 48 patients (80%) were treated successfully and 10 (16.7%) had recurrence of inflammation. CONCLUSIONS: We recommend that in patients presenting with lacrimal gland inflammation (i.e., erythema, edema, tenderness) in which the specific diagnosis cannot be made clinically and on imaging, biopsy is warranted for accurate diagnosis and appropriate treatment. We found that the majority of these patients (61.7%) had specific histopathology, and 38% had systemic diseases.
28142222 Flagellar filament structural protein induces Sjögren's syndrome-like sialadenitis in mic 2017 Jul OBJECTIVE: Sjögren's syndrome (SS) is a systemic autoimmune disease that primarily affects lacrimal and salivary glands. We previously reported that FliC derived from Escherichia coli could induce autoimmune pancreatitis-like lesions. From these results, we speculated that FliC could also induce SS-like exocrinopathy. In this study, we investigated the effects of chronic exposure to FliC on lacrimal and salivary glands and the possibility that it might lead to an autoimmune response. METHODS: C57BL/6 mice were repeatedly injected with FliC and histological changes, serum levels of cytokine/chemokines and autoantibodies were evaluated at different time points after the final injection. The presence of sialadenitis was diagnosed by histological methods. RESULTS: In FliC-treated groups, 57% of subjects developed inflammatory cell infiltrates around ducts in mandibular salivary glands, but not lacrimal glands. In addition, serum levels of total IgG, IgG1, and IgG2a were significantly higher in FliC-treated groups. Intriguingly, serum anti-SSA/Ro levels were also significantly higher in FliC-treated groups. Cytokine analysis revealed that serum levels of IL-1β, IL-12p70, IL-13, IFN-γ, IL-15, and IL-23 seemed to be higher in FliC-treated mice. CONCLUSIONS: Our data suggest that FliC-treated mice develop an SS-like phenotype. Our model may elucidate the relationship between commensal bacteria and SS.
28779847 Efficacy of intralesional sodium thiosulfate injections for disabling tumoral calcinosis: 2017 Dec INTRODUCTION: Tumoral calcinosis (TC) is a difficult-to-treat complication that can occur during several diseases such as dermatomyositis or genetic hyperphosphatemia. It is a painful and disabling condition that can lead to local complications including joint mobility reduction, cutaneous ulceration and superinfection. For the largest lesions, the treatment relies essentially on surgery. Intravenous sodium thiosulfate (STS) is efficient to treat calciphylaxis in patients undergoing hemodialysis. Local injections of STS seem efficient in superficial calcifications. OBJECTIVE: To report the efficacy and safety of intra-lesional injections of STS in tumoral calcinosis. RESULTS: We report two cases of successful intra-lesional injections of STS. A 44-year-old woman, with a history of dermatomyositis, presenting large subcutaneous calcifications in the right elbow, and a 42-year-old man, with a history of familial tumoral calcinosis, presenting large intramuscular calcifications in the right buttock, received weekly intra-lesional of 1-3g STS injections for 12 and 21 months, respectively. In both cases, the treatment relieved pain and greatly reduced the tumoral calcinosis with a very significant functional improvement without specific adverse effects. In case 1, TC size decreased from 28.7*56.0mm at baseline to 21.5*30.6mm at M12 treatment (59% reduction). In case 2, TC reduced from 167.5*204.3mm at baseline to 86.2*85.2mm at M21 treatment (79% reduction). CONCLUSION: Local injection of STS could be a promising therapeutic strategy for large and deep TC lesions and could therefore be an alternative to surgery.
28057714 Elevated IL-37, IL-18 and IL-18BP serum concentrations in patients with primary Sjögren's 2017 Mar The objectives of this study were to examine the serum levels of interleukin (IL)-37 and its clinical association in patients with primary Sjögren's syndrome (pSS) and to investigate whether or not IL-37 participates in the regulation of the pathogenesis of pSS. ELISA was used to analyse the serum levels of IL-37, total IL-18 and IL-18 binding protein (IL-18BP). The level of free IL-18 was calculated based on the mass action law. The correlations between the IL-37 serum levels with the laboratory values and the total IL-18 and IL-18BP serum levels were analyzed by a Spearman's correlation test. The serum levels of IL-37 in the patients with pSS were significantly increased compared with the healthy controls (HCs). The levels were especially elevated in the patients with pSS with positive anti-Ro/SSA and/or anti-La/SSB antibodies. Furthermore, the patients with pSS showed high serum levels of total IL-18, free IL-18 and IL-18BP compared with the HCs. Strikingly, the IL-37 levels were significantly positively correlated with the antibody levels in the patients with pSS, including rheumatoid factor, anti-Ro/SSA, and anti-La/SSB and the total IL-18 and IL-18BP serum levels. The serum levels of IL-37, which were correlated with antibody production and the serum levels of total IL-18 and IL-18BP, were elevated in the patients with pSS. IL-37, an important anti-inflammatory cytokine, may participate in the regulation of the pathogenesis of pSS.
29057505 Ductal cells of minor salivary glands in Sjögren's syndrome express LINE-1 ORF2p and APOB 2018 Feb BACKGROUND: Type I interferon activation is a hallmark event in Sjögren's syndrome. L1 retroelements stimulate plasmacytoid dendritic cells, activating the type I interferons, and are regulated by various mechanisms, including the APOBEC3 deaminases. As L1s are potential trigger factors in autoimmunity, we aimed to investigate the immunohistochemical localization of L1 ORF2p and its inhibitor APOBEC3B protein in minor salivary glands of Sjögren's syndrome patients. METHODS: Twenty minor salivary gland-tissue samples from 20 Sjögren's syndrome patients, classified according to Tarpley's histological criteria, and 10 controls were evaluated for L1 ORF2p and APOBEC3B expression via immunohistochemistry. RESULTS: L1 ORF2p was expressed in 17/20 SS patients and all controls. APOBEC3B expression was observed in 15/20 Sjögren's syndrome patients, 5/5 chronic sialadenitis, and 3/5 normal minor salivary glands. Both antibodies stained the cytoplasm of the ductal epithelial cells. Negative staining was observed in the acinar cells. L1 ORF2p-positive immunostaining was significantly lower in Tarpley IV Sjögren's syndrome patients than controls (P = .039), and APOBEC3B-positive staining was significantly lower in Tarpley I compared to Tarpley II Sjögren's syndrome patients (P = .008) and controls (P = .035). CONCLUSIONS: L1 ORF2p and APOBEC3B are expressed in the ductal epithelial cells of minor salivary glands that are among the key targets in Sjögren's syndrome. L1 ORF2p expression may promote the L1 ability to act as an intrinsic antigen in Sjögren's syndrome. The potential future use of L1 ORF2-reverse transcriptase inhibitors in autoimmunity supports further investigation of L1 epigenetic regulation by APOBEC3 enzymes.
28379971 Analysis of Th17-associated cytokines and clinical correlations in patients with dry eye d 2017 We aimed to investigate the expressions of three Th17-associated cytokines, interleukin (IL)-17A, IL-6 and IL-23, in protein and mRNA levels and their correlations with ocular surface parameters in patients with dry eye disease (DED) through a small sample size case control study. A total of 45 female subjects were divided into Sjögren's syndrome (SS) DED group, non-Sjögren's syndrome (non-SS) DED group and control group. Ocular surface disease index (OSDI) was self-answered and clinical tests including tear-film breakup time (BUT), Schirmer I test, cornea fluorescein staining (CFS) were performed. The conjunctival mRNA expressions of these cytokines were investigated by real-time polymerase chain reaction (PCR) and the levels of protein in tears were measured by mutiplex bead analysis. The correlations between cytokines and ocular surface parameters were analyzed. Results show that the expressions of IL-17A and IL-6 in protein and mRNA levels were both significantly increased in the DED group (P<0.05), and also higher in SS group comparing to the non-SS group (P<0.05). Moreover, IL-17A and IL-6 correlated well with ocular surface parameters (all P<0.05, R values range from 0.5-0.8). Despite the expression of IL-23 was significantly increased in the DED group (P<0.05), there was no significant difference found between the expressions of IL-23 in SS group and non-SS group (P>0.05) and no correlation found between the IL-23 and any ocular surface parameter (P>0.05). These findings indicates that the three Th17-associated cytokines, IL-17A, IL-6 and IL-23, play roles in the pathogenesis of DED and the expressions of IL-17A and IL-6 in tears have potential to be diagnostic biomarkers for DED.