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ID PMID Title PublicationDate abstract
29781538 Relationship between autoantibody associated with rheumatoid arthritis and tooth loss. 2018 May 21 INTRODUCTION: This study evaluated the relationship between serum Rheumatoid Factor (RF) levels and tooth loss in a community-dwelling elderly Japanese women. It was hypothesised that women with high baseline RF levels would experience greater tooth loss over 10 years than age-matched women with lower baseline serum RF levels. MATERIALS AND METHODS: The study population consisted of 197 women aged 70 years with ≥12 teeth at baseline. One hundred and twenty-four participants completed a 10-year follow-up and were divided into 2 groups according to their baseline serum RF levels as follows: RF negative (<15 U/mL; n = 114) and RF positive (>15 U/mL; n = 10). Negative binomial regression was used to investigate the relationship between baseline RFs and tooth lost over the 10-year period. RF and its interaction with the baseline number of teeth were independent variables, with 9 other adjustment covariates. RESULTS: Baseline RFs were significantly associated with tooth loss (P = .035). In addition, a statistical interaction between baseline RFs and baseline number of teeth was identified (P = .023), modifying the association between RFs and tooth loss. The adjusted incidence rate ratio (IRR) for RF-positive participants with 21 baseline teeth was 1.88 (95% confidence interval (95% CI): 0.76, 4.65). IRRs obtained for participants who had 25 baseline teeth (3.02; 95% CI: 1.03, 8.83) or 30 baseline teeth (5.47; 95% CI: 1.29, 23.13) suggested that RF-positive participants with a high number of baseline teeth would exhibit greater tooth loss than RF-negative participants. CONCLUSION: High serum RF levels were associated with a greater IRR for future tooth loss in elderly Japanese women.
29403442 Lactobacillus helveticus SBT2171 Attenuates Experimental Autoimmune Encephalomyelitis in M 2017 We recently reported that Lactobacillus helveticus SBT2171 (LH2171) inhibited the proliferation and inflammatory cytokine production of primary immune cells in vitro, and alleviated collagen-induced arthritis (CIA) in mice, a model of human rheumatoid arthritis (RA). In this study, we newly investigated whether LH2171 could relieve the severity of experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS), which is an autoimmune disease, but develop the symptoms by different mechanisms from RA. In MS and EAE, main cause of the disease is the abnormality in CD4(+) T cell immunity, whereas in RA and CIA, is that in antibody-mediated immunity. The intraperitoneal administration of LH2171 significantly decreased the incidence and clinical score of EAE in mice. LH2171 also reduced the numbers of pathogenic immune cells, especially Th17 cells, in the spinal cord at the peak stage of disease severity. Interestingly, before the onset of EAE, LH2171 administration remarkably decreased the ratio of Th17 cells to CD4(+) T cells in the inguinal lymph nodes (LNs), where pathogenic immune cells are activated to infiltrate the central nervous system, including the spinal cord. Furthermore, the expression of interleukin (IL)-6, an inflammatory cytokine essential for Th17 differentiation, decreased in the LNs of LH2171-administered mice. Moreover, LH2171 significantly inhibited IL-6 production in vitro from both DC2.4 and RAW264.7 cells, model cell lines of antigen-presenting cells. These findings suggest that LH2171 might down-regulate IL-6 production and the subsequent Th17 differentiation and spinal cord infiltration, consequently alleviating EAE symptoms.
29979768 HappyTools: A software for high-throughput HPLC data processing and quantitation. 2018 High-performance liquid chromatography (HPLC) is widely used for absolute quantitation. The advent of new columns and HPLC technology has enabled higher sample throughput, and hence, larger scale studies that perform quantitation on different sample types (e.g. healthy controls vs. patients with rheumatoid arthritis) using HPLC are becoming feasible. However, there remains a lack of methods that can analyse the increased number of HPLC samples. To address this in part, the modular toolkit HappyTools has been developed for the high-throughput targeted quantitation of HPLC measurements. HappyTools enables the user to create an automated workflow that includes retention time (tr) calibration, data extraction and the calculation of several quality criteria for data curation. HappyTools has been tested on a biopharmaceutical standard and previously published clinical samples. The results show comparable accuracy between HappyTools, Waters Empower and ThermoFisher Chromeleon. However, HappyTools offered superior precision and throughput when compared with Waters Empower and ThermoFisher Chromeleon. HappyTools is released under the Apache 2.0 license, both the source code and a Windows binary can be freely downloaded from https://github.com/Tarskin/HappyTools.
29083070 Breastfeeding and autoimmunity: Programing health from the beginning. 2018 Jan Breast milk is not only a completely adapted nutrition source for the newborn but also an impressive array of immune-active molecules that afford protection against infections and shape mucosal immune responses. Decisive imprinting events might be modulated during the first months of life with potential health long-term effects, enhancing the importance of breastfeeding as a major influence on the immune system correct development and modifying disease susceptibility. The aim of this review was to clarify the link between breastfeeding and autoimmune diseases, inquiring the related mechanisms, based on data available in the literature. Being breastfed was associated with a lower incidence of diabetes, celiac disease, multiple sclerosis and asthma, explained by the protection against early infections, anti-inflammatory properties, antigen-specific tolerance induction, and regulation of infant's microbiome. The protective role of human milk in idiopathic juvenile arthritis, rheumatoid arthritis, and inflammatory bowel diseases remains controversial. On the other hand, the breastfeeding mother faces a health-challenging period in life. High levels of prolactin may lead either to the development of autoimmune diseases in susceptible mothers or exacerbations of current immune-mediated disorders. These features raise the question if mothers with autoimmune diseases, mainly systemic lupus erythematosus, should avoid breastfeeding.
29543213 [Ventral decompression techniques in patients with traumatic and non-traumatic atlanto-axi 2018 Compression of the caudal medulla oblongata and ventral portions of the spinal cord is the most dangerous complication of atlanto-axial dislocation (AAD). AIM: The study objective was to improve surgical management of patients with ventral compression of the spinal cord in the setting of AAD of various genesis. MATERIAL AND METHODS: We analyzed treatment outcomes in 250 patients with C1 and C2 injuries and diseases for the period between 2002 and 2016. Persistent ventral compression of the neural structures in the setting of AAD was detected in 34 (13.6%) patients. Anterior or posterior dislocation was in 21 patients, vertical dislocation occurred in 7 patients, and mixed (anterior and vertical) occurred in 6 cases. The causes of AAD included odontoid fractures (21 patients, 61.8%), Jefferson fractures (6 patients, 17.6%), atlas transverse ligament rupture (1 patient, 2.9%), rheumatoid arthritis (4 patients, 11.8%), and nonspecific spondylitis (2 patients, 5.9%). RESULTS: All dislocations were divided into Halo-tractable and Halo-intractable ones. In 24 cases, ventral decompression was achieved due to Halo reposition. Additional resection of a compressing substrate was performed through the submandibular approach in 4 patients, through the transoral approach in 5 patients, and through the transnasal approach in 1 case. In the postoperative period, complications in the form of pharyngeal edema developed in 1 patient after transoral decompression. In the other cases, there were no postoperative complications. All patients had improvement in their condition in the form of regression of a neurological deficit. CONCLUSION: Halo reposition is a technique eliminating, completely or partially, ventral compression in certain traumatic and non-traumatic dislocations. The choice of a surgical corridor should be performed after preliminary Halo correction. If the nasopalatine line runs in the odontoid neck projection, the submandibular approach may be used in the case of a Halo-tractable dislocation, and the endonasal approach may be used in the case of a Halo-intractable dislocation.
30048820 A comparative analysis of articular bone in large cohort of patients with chronic inflamma 2018 Nov Chronic inflammatory diseases are associated with bone loss. While the occurrence of systemic bone loss is well described in chronic inflammatory diseases, the impact of these conditions on articular bone has not been systematically investigated. Recent refinements in high-resolution CT assessment of the joints now allow the accurate measure of articular bone composition. In this study 476 subjects comprising healthy individuals and patients with anticitrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA), ACPA-negative RA, Crohn's disease (CD), ulcerative colitis (UC), psoriasis (PsO) and psoriatic arthritis (PsA) were subjected to high-resolution quantitative computed tomography (HR-pQCT) of the hand. Metacarpal heads were assessed for total, trabecular and cortical volumetric bone mineral density (vBMD). Only ACPA+RA, but not the remaining inflammatory diseases (ACPA-RA, CD, UC, PsO, PsA) showed significant (p < 0.001) loss of articular bone affecting both the trabecular and the cortical compartments. Age and body mass index were also associated with articular bone changes, the former with lower, the latter with higher articular bone mass. In multivariate models, presence of ACPA+RA was an independent factor for articular bone loss. Among chronic inflammatory diseases ACPA+RA is the most potent precipitator for articular bone loss pointing out the role of autoimmunity in the development of articular bone disease in the context of chronic inflammatory disease.
30413164 Juvenile idiopathic arthritis managed in the new millennium: one year outcomes of an incep 2018 Nov 9 BACKGROUND: The advent of new treatments for Juvenile Idiopathic Arthritis (JIA) has prompted interest in systematically studying the outcomes of patients treated in the 'modern era'. Such data provide both benchmarks for assessing local outcomes and important information for use in counselling families of newly diagnosed patients. While data are available for cohorts in Europe and North America, no such data exist for Australian patients. The aim was to examine the demographics, treatment and outcomes at 12 months of an inception cohort of newly diagnosed patients with JIA at a single tertiary referral paediatric rheumatology centre in Australia. METHODS: Retrospective review of prospectively collected data from patients newly diagnosed with JIA between 2010 and 2014 at the Royal Children's Hospital in Melbourne. RESULTS: One hundred thirty four patients were included (62% female). Oligoarthritis was the single largest category of JIA (36%) and rheumatoid factor positive polyarthritis the least common (2%). Undifferentiated JIA accounted for 13% of patients and was the third largest category. Across the cohort 94% received NSAIDs, 53% oral steroids, 62% methotrexate and 15% a biologic DMARD. Intra-articular steroids were used in 62%, most commonly in the oligoarticular subtype (94%). 95% of patients achieved a joint count of zero at a median of 4.1 months, however flares occurred in 42%. At 12 months 65% had no active joint disease, though more than half remained on medication. CONCLUSION: Australian children with JIA managed in the modern era have similar characteristics and achieve short term outcomes comparable to cohorts in Europe and North America, with high rates of joint remission in the first 12 months of follow-up but with a significant relapse rate and requirement for ongoing medication.
29181736 Adoptive Induced Antigen-Specific Treg Cells Reverse Inflammation in Collagen-Induced Arth 2018 Mar Rheumatoid arthritis (RA) is a systemic autoimmune disease that may cause bone damage and worsening disability. Manipulating antigen-specific Treg cells is a promising approach to treat autoimmune disease since the immune suppressive function of Treg cells has the feature of antigen specificity which could avoid overall immune suppression. It has been known that the function of Treg cells is impaired in RA, and adoptive transfer of Treg cells is effective in suppressing RA. Here, we designed a new approach to generate antigen-specific Treg cells by culturing CD4(+) T cells from mice with RA onset, and we also proved that the adoptive transfer of these antigen-specific Treg cells reversed the collagen-induced arthritis (CIA) progression by suppressing the key inflammatory cytokine TNF-α. Further analysis showed that the transferred Treg cells were stable in vivo. These findings suggest this novel approach may have clinical applications for treatment of autoimmunity, including RA and other autoimmune disorders.
30213634 Depleting the carboxy-terminus of human Wnt5a attenuates collagen-induced arthritis in DBA 2018 Oct 12 Wnt5a signalling plays pathological roles in synovial inflammation and bone destruction. In the present study, we designed four human Wnt5a-based DNA recombinants and detected their effects on immunogenicity and anti-rheumatism in a collagen-induced arthritis (CIA) model. Histomorphometry and micro-CT scanning showed that the phWnt5a-NL was superior to other recombinants because it resulted in decreased severity of arthritis, histopathological scores of synovial inflammation and bone erosion in CIA mice. In addition, ELISA and TRAP staining showed that the phWnt5a-NL-immunized CIA mice had reductions in the serum concentrations of the rheumatoid-associated cytokines IL-1β and RANKL and in osteoclastogenesis. Furthermore, flow cytometry showed that the phWnt5a-NL treatment increased the percentage of Treg cells. Finally, western blotting analysis showed that the phWnt5a-NL-immunization interrupted β-catenin and JNK expression in osteoclast precursors derived from the CIA mice. The results suggest that depleting the carboxy-terminus in hWnt5a-based DNA recombinants may be beneficial for the treatment of chronic inflammatory disorders involving bone resorption.
28552625 The current status and unmet needs in the management of psoriatic arthritis: Viewpoint fro 2018 May BACKGROUND/PURPOSE: To analyze the real-world clinical practice for the treatment of psoriatic arthritis (PsA) and to assess physicians' prescription, difficulties in diagnosis, therapeutic strategy, rationales for biologic therapies and unmet needs in Taiwan. METHODS: We conducted a nationwide cross-sectional observational study by face-to-face in depth interviews with 50 rheumatologists and 30 dermatologists who took care of patients with PsA. RESULTS: The major procedures for recognizing PsA included joint, skin and nail examinations, radiographic imaging, and medical history. More dermatologists established the diagnosis when psoriatic patients with arthritis didn't present with rheumatoid factors (p < 0.05). For milder arthritis, physicians tended to prescribe etanercept in combination with conventional disease-modifying antirheumatic drugs (DMARDs). The efficacy, safety, retention rate, and non-parenteral administration are the major concerns of physicians which are also the primary unmet needs in the current management of PsA. CONCLUSION: This survey showed the status quo in Taiwan of the clinical management for PsA including diagnostic difficulties, therapeutic consideration, rationales for biologic DMARDs selection and unmet needs in treatment. It has indicated that interdisciplinary collaboration may further improve the quality for PsA care. These results may help establish new strategy to develop next generation biologics.
29880010 Secukinumab provides rapid and sustained pain relief in psoriatic arthritis over 2 years: 2018 Jun 7 BACKGROUND: Pain is one of the most important domains affecting health-related quality of life (HRQoL) in patients with psoriatic arthritis (PsA). Secukinumab has demonstrated rapid and sustained improvements in signs and symptoms, including HRQoL, among patients with active PsA. This analysis evaluates the effect of secukinumab on patient-reported pain in PsA through 104 weeks of treatment. METHODS: Pain was assessed through week 104 using clinically relevant measures, including change from baseline in a pain visual analog scale (VAS) and Short Form-36 (SF-36) bodily domain scores; proportion of patients reporting improvements equal to or better than minimum clinically meaningful differences in the pain VAS and SF-36 bodily pain domain scores; and proportion of patients with no, moderate, or extreme pain/discomfort measured by the EuroQoL 5-Dimension 3-Level Questionnaire (EQ-5D-3 L) pain item scores. Correlations of pain measures were analyzed using Pearson's correlation coefficient. Pre-specified analyses of TNF-naïve patients and patients who stopped TNF-inhibitors (TNFis) due to inadequate responses or safety/tolerability (TNF-IR patients) were performed using "as-observed data." RESULTS: Mean improvements from baseline in pain VAS scores were greater with secukinumab versus placebo by week 3 (- 16.9; P < 0.0001 with secukinumab 300 mg and - 12.6; P < 0.05 with secukinumab 150 mg) and sustained through week 104. SF-36 bodily pain domain scores were significantly greater with 300 mg secukinumab and secukinumab 150 mg versus placebo by week 4 (16.2 and 16.3, respectively; P < 0.0001 for both), and these changes were maintained through week 104. With both secukinumab 300 mg and secukinumab 150 mg, improvements equal to or better than the minimum clinically meaningful differences in pain VAS and SF-36 bodily pain were significant versus placebo at week 3 and week 4, respectively. At week 4, 15%, 9%, and 5% of patients receiving secukinumab 300 mg, secukinumab 150 mg, and placebo, respectively, reported "no pain/discomfort" measured by EQ-5D-3 L; these proportions increased to week 104 with both secukinumab doses. Similarly, improvements in pain measures were significant in both TNF-naïve and TNF-IR patients. CONCLUSION: Secukinumab provided rapid and sustained pain relief in PsA over 2 years of treatment. Improvements in pain were reported regardless of prior exposure to TNFis. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01752634 . Registered on 19 December 2012.
30282561 The blood-brain barrier, TWEAK, and neuropsychiatric involvement in human systemic lupus e 2018 Nov OBJECTIVE: A prevailing hypothesis for neuropsychiatric involvement in systemic lupus erythematosus (SLE) and primary Sjögren's syndrome is that brain reactive autoantibodies enter the brain through a disrupted blood-brain barrier. Our aim was to investigate whether TNF-like weak inducer of apoptosis (TWEAK) plays a role in cerebral involvement in human SLE and primary Sjögren's syndrome, and whether an impaired blood-brain barrier is a prerequisite for neuropsychiatric manifestations. METHODS: TWEAK was measured in the cerebrospinal fluid and serum and compared with markers of blood-brain barrier permeability (Q-albumin and MRI contrast-enhanced lesions) and S100B, an astrocyte activation marker in 50 SLE and 52 primary Sjögren's syndrome patients. Furthermore, we estimated the general intrathecal B-cell activation (IgG index), measured anti-NR2 antibodies in cerebrospinal fluid, and explored whether these variables were associated with neuropsychiatric manifestations. RESULTS: No associations were found between TWEAK in the cerebrospinal fluid or serum and neuropsychiatric manifestations in SLE nor in primary Sjögren's syndrome patients. Furthermore, no associations were found between neuropsychiatric manifestations and indicators of blood-brain barrier integrity or astroglial activity. Anti-NR2 antibodies were associated with impaired visuospatial processing (odds ratio 4.9, P = 0.03) and motor functioning (odds ratio 6.0, P = 0.006). CONCLUSION: No clinical neuropsychiatric manifestations could be attributed to impaired integrity of the blood-brain barrier, or to TWEAK levels in cerebrospinal fluid or serum in either patient group. The TWEAK concentration was considerably higher in the cerebrospinal fluid than in blood, which indicates intrathecal production. We hypothesize that increased TWEAK and S100B result from immunological stress caused by brain-reactive antibodies produced by brain residing immune cells.
29922285 Autoantibodies to Cytosolic 5'-Nucleotidase 1A in Primary Sjögren's Syndrome and Systemic 2018 INTRODUCTION: Autoantibodies to cytosolic 5'-nucleotidase 1A (cN-1A; NT5C1A) have a high specificity when differentiating sporadic inclusion body myositis from polymyositis and dermatomyositis. In primary Sjögren's syndrome (pSS) and systemic lupus erythematosus (SLE) anti-cN-1A autoantibodies can be detected as well. However, various frequencies of anti-cN-1A reactivity have been reported in SLE and pSS, which may at least in part be explained by the different assays used. Here, we determined the occurrence of anti-cN-1A reactivity in a large number of patients with pSS and SLE using one standardized ELISA. METHODS: Sera from pSS (n = 193) and SLE patients (n = 252) were collected in five European centers. Anti-cN-1A, anti-Ro52, anti-nucleosome, and anti-dsDNA reactivities were tested by ELISA (Euroimmun AG) in a single laboratory. Correlations of anti-cN-1A reactivity with demographic data and clinical data (duration of disease at the moment of serum sampling, autoimmune comorbidity and presence of muscular symptoms) were analyzed using SPSS software. RESULTS: Anti-cN-1A autoantibodies were found on average in 12% of pSS patients, with varying frequencies among the different cohorts (range: 7-19%). In SLE patients, the anti-cN-1A positivity on average was 10% (range: 6-21%). No relationship was found between anti-cN-1A reactivity and the presence or absence of anti-Ro52, anti-nucleosome, and anti-dsDNA reactivity in both pSS and SLE. No relationship between anti-cN-1A reactivity and duration of disease at the moment of serum sampling and the duration of serum storage was observed. The frequency of muscular symptoms or viral infections did not differ between anti-cN-1A-positive and -negative patients. In both disease groups anti-cN-1A-positive patients suffered more often from other autoimmune diseases than the anti-cN-1A-negative patients (15 versus 5% (p = 0.05) in pSS and 50 versus 30% (p = 0.02) in SLE). CONCLUSION: Our results confirm the relatively frequent occurrence of anti-cN-1A in pSS and SLE patients and the variation in anti-cN-1A reactivity between independent groups of these patients. The explanation for this variation remains elusive. The correlation between anti-cN-1A reactivity and polyautoimmunity should be evaluated in future studies. We conclude that anti-cN-1A should be classified as a myositis-associated-, not as a myositis-specific-autoantibody based on its frequent presence in SLE and pSS.
30598637 The TGF-β1 Signaling Pathway as an Attractive Target in the Fibrosis Pathogenesis of Sjö 2018 Transforming growth factor β1 (TGF-β1) plays a crucial role in the induction of fibrosis, often associated with chronic phases of inflammatory diseases contributing to marked fibrotic changes that compromise normal organ function. The TGF-β1 signal exerts its biological effects via the TGF-β/SMAD/Snail signaling pathway, playing an important pathogenic role in several fibrotic diseases. It has as yet been poorly investigated in the chronic autoimmune disease Sjögren's syndrome (SS). Here, we firstly tested, by immunohistochemistry, whether the TGF-β1/SMAD/Snail signaling pathway is triggered in human pSS salivary glands (SGs). Next, healthy salivary gland epithelial cell (SGEC) cultures derived from healthy donors were exposed to TGF-β1 treatment, and the relative gene and protein levels of SMAD2/3/4, Snail, E-cadherin, vimentin, and collagen type I were compared by semiquantitative RT-PCR, quantitative real-time PCR, and Western blot analysis. We observed, both at gene and protein levels, higher expression of SMAD2, 3, and 4 and Snail in the SGEC exposed by TGF-β1 compared to untreated healthy SGEC. Additionally, in TGF-β1-treated samples, we found a significant reduction in the epithelial phenotype marker E-cadherin and an increase in the mesenchymal phenotype markers vimentin and collagen type I compared to those in untreated SGEC, indicating that TGF-β1 induces the EMT via the TGF-β1/SMAD/Snail signaling pathway. Therefore, by using the specific TGF-β receptor 1 inhibitor SB-431542 in healthy SGEC treated with TGF-β1, we showed a significant reduction of the fibrosis markers vimentin and collagen type I while the epithelial marker E-cadherin returns to levels similar to untreated healthy SGEC. These data demonstrate that TGF-β1 is an important key factor in the transition phase from SG chronic inflammation to fibrotic disease. Characteristic changes in the morphology and function of TGF-β1-treated healthy SGEC further confirm that TGF-β1 plays a significant role in EMT-dependent fibrosis.
30472652 Phosphatidylinositol 3-kinase delta pathway: a novel therapeutic target for Sjögren's syn 2019 Feb BACKGROUND: The phosphatidylinositol 3-kinase delta isoform (PI3Kδ) belongs to an intracellular lipid kinase family that regulate lymphocyte metabolism, survival, proliferation, apoptosis and migration and has been successfully targeted in B-cell malignancies. Primary Sjögren's syndrome (pSS) is a chronic immune-mediated inflammatory disease characterised by exocrine gland lymphocytic infiltration and B-cell hyperactivation which results in systemic manifestations, autoantibody production and loss of glandular function. Given the central role of B cells in pSS pathogenesis, we investigated PI3Kδ pathway activation in pSS and the functional consequences of blocking PI3Kδ in a murine model of focal sialoadenitis that mimics some features of pSS. METHODS AND RESULTS: Target validation assays showed significant expression of phosphorylated ribosomal protein S6 (pS6), a downstream mediator of the phosphatidylinositol 3-kinase delta (PI3Kδ) pathway, within pSS salivary glands. pS6 distribution was found to co-localise with T/B cell markers within pSS aggregates and the CD138+ plasma cells infiltrating the glands. In vivo blockade of PI3Kδ activity with seletalisib, a PI3Kδ-selective inhibitor, in a murine model of focal sialoadenitis decreased accumulation of lymphocytes and plasma cells within the glands of treated mice in the prophylactic and therapeutic regimes. Additionally, production of lymphoid chemokines and cytokines associated with ectopic lymphoneogenesis and, remarkably, saliva flow and autoantibody production, were significantly affected by treatment with seletalisib. CONCLUSION: These data demonstrate activation of PI3Kδ pathway within the glands of patients with pSS and its contribution to disease pathogenesis in a model of disease, supporting the exploration of the therapeutic potential of PI3Kδ pathway inhibition in this condition.
29953016 IgG4-related retroperitoneal fibrosis overlapping with primary biliary cirrhosis and prima 2018 Jun RATIONALE: IgG4-related disease (IgG4-RD) is a chronic fibro-inflammatory disorder which is characterized by elevated levels of serum IgG4 and infiltration of IgG4-bearing plasma cells in the involved organs. Primary biliary cirrhosis (PBC) and Primary Sjögren's syndrome (pSS) are both distinct from IgG4-related disease. We herein describe a Chinese patient with IgG4-related RPF overlapping with PBC and pSS. PATIENT CONCERNS: We report a case of 69-year-old male with recurrent lower abdominal pain for 10 months. Laboratory data showed elevated erythrocyte sedimentation rate and hepatobiliary enzymes, renal dysfunction, high titers of antinuclear antibody, anti-SS-A antibody and anti-mitochondrial type 2, high immunoglobulin (Ig) G levels and elevated serum IgG4 (9 g/L). Contrast-enhanced computed tomography and magnetic resonance imaging were suggestive of retroperitoneal fibrosis and unilateral ureteral occlusion. Immunohistochemical staining for IgG4 did not demonstrate infiltration of IgG4-positive plasma cells in the retroperitoneal mass, but revealed significant infiltration of lymphocytoplasma cells as well as fibrosis and fibrin accumulation. DIAGNOSES: The patient was diagnosed with IgG4-related retroperitoneal fibrosis based on the International Consensus Diagnostic Criteria. He was also diagnosed with primary biliary cirrhosis and primary Sjögren's syndrome. INTERVENTIONS: 250 mg ursodeoxycholic acid was administered twice daily, and prednisolone was initiated at a dose of 40 mg/day and then tapered to 25 mg after 45 days. OUTCOMES: The size of the retroperitoneal soft tissue mass gradually reduced and the abnormal laboratory parameters were restored to normal. LESSONS: This rare clinical condition has seldom been reported in the literature, which suggests that common immunogenetic factors may be involved in the development of IgG-related RPF, PBC and pSS.
29217121 Diagnostic and treatment effects of sialendoscopy for patients with swelling of the paroti 2018 Aug Between August 2009 and May 2016, 74 patients underwent sialoendoscopic surgery. 32 patients had parotid gland disease and 9 patients had intermittent swelling of the parotid gland and sialoliths were not detected with CT imaging. 4 patients were diagnosed with idiopathic Stensen's duct stenosis. Sialendoscopy directly confirmed Stensen's duct stenosis in 2 patients. However, the sialendoscope was unable to be inserted in the other 2 patients, who had stenosis of the orifice of the Stensen's duct. Balloon expansion of the duct was performed in these 2 patients and a steroid drug was injected into the duct in one patient. Complete remission was archived in one patient treated with sialendoscopy. Three patients had sialolithiasis. Microsialoliths and/or white floating matter was observed and removed using sialendoscopy. All patients experienced complete remission. In cases of Sjögren syndrome and recurrent parotitis, sialendoscopic surgery was performed, but the symptoms showed no improvement. For patients with microsialoliths, sialendoscopy may be most useful for diagnosis and treatment when the sialoliths are not detected with CT imaging. At present, sialendoscopic surgery have limitation in the treatment of Stensen's duct stenosis and may similarly have limitation in the treatment of Sjögren's syndrome and recurrent parotitis.
29926992 Inverse correlation between the number of CXCR3(+) macrophages and the severity of inflamm 2018 Aug BACKGROUND: Mechanisms underlying immune cells' recruitment and activation into the inflammatory lesions of lip salivary glands (LSGs) from primary Sjögren's syndrome (pSS) patients are incompletely understood. Chemokines play pivotal roles in these processes, so we investigated the clinical significance of chemokine receptor CXCR3 and its ligands in the autoimmune lesions of pSS. METHODS: We histologically determined the grade of LSG samples from 22 patients with pSS and subjected the samples to immunofluorescence analysis to determine the expressions of CXCR3 and its ligands: CXCL9, CXCL10, and CXCL11. To identify the immune cells expressing CXCR3 in the LSGs, we performed double immunofluorescence analysis using antibodies against CD3 (pan-T cells), CD80 (M1 macrophages), CD163 (M2 macrophages), and CD123 (plasmacytoid dendritic cells: pDCs). The relationship between the grade of lymphocytic infiltration and the number of positively stained cells was analyzed by Spearman's rank correlation test. RESULTS: The expressions of CXCL9 and CXCL10 showed particularly intense staining in the LSG samples' ductal cells. The CXCR3 expression was detected mainly in CD80(+) and CD163(+) macrophages. The number of CXCR3(+) CD163(+) macrophages inversely correlated with the LSG inflammatory lesions' severity (rs = -0.777, P < 0.001). CONCLUSIONS: Our results suggest that the enhanced production of CXCL9 and CXCL10 from ductal cells results in the CXCR3(+) macrophages' migration. There was an inverse correlation between these two parameters: that is, the number of CXCR3(+) CD163(+) macrophages decreased as the lymphocytic infiltration grade increased. Although CXCR3 is expressed in all of the innate immune cells, CXCR3(+) CD163(+) M2 macrophages may contribute to the anti-inflammatory functions in pSS lesions.
29505322 Activation of Stimulator of Interferon Genes (STING) and Sjögren Syndrome. 2018 Jul Sjögren syndrome (SS), a chronic autoimmune disorder causing dry mouth, adversely affects the overall oral health in patients. Activation of innate immune responses and excessive production of type I interferons (IFNs) play a critical role in the pathogenesis of this disorder. Recognition of nucleic acids by cytosolic nucleic acid sensors is a major trigger for the induction of type I IFNs. Upon activation, cytosolic DNA sensors can interact with the stimulator of interferon genes (STING) protein, and activation of STING causes increased expression of type I IFNs. The role of STING activation in SS is not known. In this study, to investigate whether the cytosolic DNA sensing pathway influences SS development, female C57BL/6 mice were injected with a STING agonist, dimethylxanthenone-4-acetic acid (DMXAA). Salivary glands (SGs) were studied for gene expression and inflammatory cell infiltration. SG function was evaluated by measuring pilocarpine-induced salivation. Sera were analyzed for cytokines and autoantibodies. Primary SG cells were used to study the expression and activation of STING. Our data show that systemic DMXAA treatment rapidly induced the expression of Ifnb1, Il6, and Tnfa in the SGs, and these cytokines were also elevated in circulation. In contrast, increased Ifng gene expression was dominantly detected in the SGs. The type I innate lymphoid cells present within the SGs were the major source of IFN-γ, and their numbers increased significantly within 3 d of treatment. STING expression in SGs was mainly observed in ductal and interstitial cells. In primary SG cells, DMXAA activated STING and induced IFN-β production. The DMXAA-treated mice developed autoantibodies, sialoadenitis, and glandular hypofunction. Our study demonstrates that activation of the STING pathway holds the potential to initiate SS. Thus, apart from viral infections, conditions that cause cellular perturbations and accumulation of host DNA within the cytosol should also be considered as possible triggers for SS.
28771678 Lymphocytic hidradenitis: A distinctive histopathological finding of annular erythema of S 2018 Aug BACKGROUND/OBJECTIVES: Lymphocytic hidradenitis is a non-specific histopathological feature observed in many dermatoses such as lupus erythematosus, morphea or scleroderma. When it occurs it is usually accompanied by the other distinctive histological features of those conditions. Isolated lymphocytic hidradenitis is uncommon and its clinical features and associated underlying medical conditions are still undetermined. METHODS: We performed a retrospective review of patients who clinically presented with annular erythema between 2000 and 2016. Altogether, 30 patients with a histopathological presentation of isolated lymphocytic hidradenitis were identified. Their following characteristics were recorded: clinical features, number and localisation of lesions, serology and other associated medical conditions. RESULTS: Isolated lymphocytic hidradenitis was found most frequently in middle-aged women. Most patients (n = 28, 93%) presented with many annular erythematous patches and plaques with mild pruritus; 22 (73%) had the SS-A antibody and 17 (57%) met the diagnostic criteria of Sjögren syndrome. Among these patients, 11 had primary and six had secondary Sjögren syndrome associated with systemic lupus erythematosus. Altogether 15 (50%) patients tested positive for a high titre of the antinuclear autoantibody. Other underlying diseases identified during the follow-up period include cryoglobulinaemia, angioimmunoblastic T-cell lymphoma, autoimmune hepatitis, hepatitis C infection and toxic thyroid goitre. CONCLUSIONS: Lymphocytic hidradenitis is a microscopic finding associated with annular erythemas of Sjögren syndrome. Systemic survey for sicca symptoms and work up for autoimmune diseases, including antinuclear antibodies, SS-A, SS-B antibodies, cryoglobulin, lymphoma, viral and autoimmune hepatitis should be performed to facilitate the correct diagnosis.