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ID PMID Title PublicationDate abstract
29302207 Role of inflammasomes in inflammatory autoimmune rheumatic diseases. 2018 Jan Inflammasomes are intracellular multiprotein complexes that coordinate anti-pathogenic host defense during inflammatory responses in myeloid cells, especially macrophages. Inflammasome activation leads to activation of caspase-1, resulting in the induction of pyroptosis and the secretion of pro-inflammatory cytokines including interleukin (IL)-1β and IL-18. Although the inflammatory response is an innate host defense mechanism, chronic inflammation is the main cause of rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), and Sjögren's syndrome (SS). Since rheumatic diseases are inflammatory/autoimmune disorders, it is reasonable to hypothesize that inflammasomes activated during the inflammatory response play a pivotal role in development and progression of these diseases. Indeed, previous studies have provided important observations that inflammasomes are actively involved in the pathogenesis of inflammatory/autoimmune rheumatic diseases. In this review, we summarize the current knowledge on several types of inflammasomes during macrophage-mediated inflammatory responses and discuss recent research regarding the role of inflammasomes in the pathogenesis of inflammatory/autoimmune rheumatic diseases. This avenue of research could provide new insights for the development of promising therapeutics to treat inflammatory/autoimmune rheumatic diseases.
29265115 Chikungunya: Molecular Aspects, Clinical Outcomes and Pathogenesis. 2017 Nov The alarming worldwide emergence of the chikungunya virus began in the last decade. Since the first autochthonous transmission in Mexico in November of 2014, the virus has spread throughout the country, resulted in multiple outbreaks. This virus produces an acute and self-limiting disease characterized by fever, polyarthralgia, myalgia, exanthema, and general malaise. It is transmitted to humans by the bite of Aedes aegypti and A. albopictus mosquitoes. The fact that the clinical presentation is similar to that produced by other arboviruses complicates its clinical diagnosis. The chronic stage of the disease can cause severe consequences lasting months or years, from local arthralgia to rheumatoid arthritis. In this review, we emphasize the public health threat posed by this highly disabling emerging disease, the clinical outcomes, and its possible physiopathological process. We outline the diagnosis and the impact that this virus has had in Mexico since its introduction.
29226345 Palisading neutrophilic and granulomatous dermatitis as a presentation of Hodgkin lymphoma 2018 Feb Palisaded neutrophilic and granulomatous dermatitis (PNGD) is a histopathological diagnosis, characterized by a pattern of granulomatosis, which may be associated with leukocytoclastic vasculitis. PNGD most commonly occurs in association with systemic inflammatory disorders, typically autoimmune conditions, such as rheumatoid arthritis and systemic lupus erythromatosus. There are very rare reports of PNGD in patients with lymphoma. We report the case of a 53-year-old female with an erythematous, papular eruption occurring in association with Hodgkin lymphoma. Histopathological evaluation of the rash confirmed PNGD. To the best of our knowledge, this is the first case of PNGD occurring in association with Hodgkin lymphoma. Although extremely rare, underlying malignancy should be considered in patients with PNGD, particularly in individuals with constitutional symptoms and the absence of an obvious inflammatory etiology.
28250461 The emerging safety profile of JAK inhibitors in rheumatic disease. 2017 Apr Tofacitinib is the first Janus kinase (JAK) inhibitor commercially approved for the treatment of rheumatoid arthritis. This compound and a number of other JAK inhibitors are currently being tested in phase II and III trials for the treatment of a variety of autoimmune inflammatory diseases. Whereas a characteristic safety profile is emerging for some JAK inhibitors, differences between individual agents might emerge on the basis of distinct potency against their molecular targets. Similarly to biological therapy, JAK inhibition can lead to serious and opportunistic infections, and viral infections seem to be particularly frequent. Although no malignancy signals have been identified to date, long-term follow-up and further research are needed to understand the risk of malignancy associated with these compounds. As is the case for biologic agents, vaccination is important to mitigate the risks of these emerging therapies.
28525857 Industrial air emissions, and proximity to major industrial emitters, are associated with 2017 Aug OBJECTIVE: To determine the association of anti-citrullinated antibodies (ACPA) with the ambient air pollutants fine particulate matter (PM2.5) and sulfur dioxide (SO2). METHODS: The CARTaGENE first-wave cohort includes 20,000 general population subjects from Quebec (Canada). On a sample of unselected 1586 subjects, we determined serum, ACPA and performed multivariable logistic regression, for the outcome of positive ACPA, assessing for independent effects of our air pollution variables, adjusting for age, sex, smoking, and French Canadian origin. Two models assessed distance to main industrial emitters of PM(2.5), and of SO2, and two models assessed tons of SO2 and of PM(2.5) annual emissions. We also assessed associations with PM2.5 regional ambient concentrations estimated with satellite imagery. RESULTS: Adjusted analyses suggested a positive association between annual industrial PM(2.5) and SO2 emissions and the presence of ACPA antibodies (OR: 1.02, 95%CI 1.00-1.04 per 10t of PM2.5 and 100t of SO2). The data were also consistent with a negative association between the presence of ACPA, and distance to a major industrial emitter of both PM(2.5) and SO(2). We found no association with PM2.5 estimates of ambient levels. CONCLUSIONS: These analyses suggest that exposure to industrial emissions of air pollutants is related to ACPA positivity.
27859438 Position Paper from the Portuguese Association of Hospital Pharmacists for biosimilar ther 2017 Apr WHAT IS KNOWN AND OBJECTIVE: Biopharmaceuticals are an important class of drugs for the treatment of autoimmune/inflammatory and oncologic diseases. With patent expiries, biotechnological manufacturers can now develop biosimilar drugs. Due to timeliness of introducing new and more complex biosimilars, the Portuguese Association of Hospital Pharmacists gathered to develop a common positioning on the use of biosimilar monoclonal antibodies. MAIN ISSUES: The European pathway to biosimilar approval was developed to improve affordability and access to biological therapies, but it remains a work in progress because unresolved issues remain. Due to the present reality of biosimilar monoclonal antibodies, hospital pharmacists must play an important role in ensuring the safe, effective and cost-effective use of biosimilars in health systems; and educating healthcare administrators, providers, legislators, policymakers, payors and patients about these products. WHAT IS NEW AND CONCLUSION: The conclusions presented in this work focused on the proposal for optimal biosimilar prescription criteria, the preparation of original biologics and biosimilars in the pharmacy, the management and selection of suppliers, extrapolation issues, the specific role of pharmacovigilance and risk management for the optimal use of biosimilar monoclonal antibodies.
28664158 Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases. 2017 The identification of new bioactive compounds derived from medicinal plants with significant therapeutic properties has attracted considerable interest in recent years. Such is the case of the Tripterygium wilfordii (TW), an herb used in Chinese medicine. Clinical trials performed so far using its root extracts have shown impressive therapeutic properties but also revealed substantial gastrointestinal side effects. The most promising bioactive compound obtained from TW is celastrol. During the last decade, an increasing number of studies were published highlighting the medicinal usefulness of celastrol in diverse clinical areas. Here we systematically review the mechanism of action and the therapeutic properties of celastrol in inflammatory diseases, namely, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel diseases, osteoarthritis and allergy, as well as in cancer, neurodegenerative disorders and other diseases, such as diabetes, obesity, atherosclerosis, and hearing loss. We will also focus in the toxicological profile and limitations of celastrol formulation, namely, solubility, bioavailability, and dosage issues that still limit its further clinical application and usefulness.
32264318 Dendritic polyglycerol anions for the selective targeting of native and inflamed articular 2017 Jun 28 The destruction of articular cartilage is a critical feature in joint diseases. An approach to selectively target the damaged tissue is promising for the development of diagnostic and therapeutic agents. We herein present the interaction of dendritic polyglycerol (dPG) anions with native and inflamed cartilage. Confocal laser scanning microscopy revealed the inert character of dPG and low functionalized dPG bisphosphonate (dPGBP(7%)) toward cartilage in vitro. An enhanced binding was observed for highly functionalized dPG bisphosphonate, sulfate, and phosphate, which additionally showed a higher affinity to IL-1β treated tissue. The mixed anion containing sulfate and bisphosphonate groups exhibited an exceptionally high affinity to cartilage and strongly bound to collagen type II, as shown by a normalized fluorescence-based binding assay. All polyglycerol anions, except dPGBP(7%), were taken up by chondrocytes within 24 h and no cytotoxicity was found up to 10(-5) M. In a rheumatoid arthritis model, dPGBP(7%) accumulated in mineralized compartments of inflamed joints and showed an increasing affinity to cartilage with higher clinical scores, as evident from histological examinations. For dPGS no interaction with bone but a strong binding to cartilage, independent of the score, was demonstrated. These results make dPG anions promising candidates for the selective targeting of cartilage tissue.
28785300 Pathway-Based Kernel Boosting for the Analysis of Genome-Wide Association Studies. 2017 The analysis of genome-wide association studies (GWAS) benefits from the investigation of biologically meaningful gene sets, such as gene-interaction networks (pathways). We propose an extension to a successful kernel-based pathway analysis approach by integrating kernel functions into a powerful algorithmic framework for variable selection, to enable investigation of multiple pathways simultaneously. We employ genetic similarity kernels from the logistic kernel machine test (LKMT) as base-learners in a boosting algorithm. A model to explain case-control status is created iteratively by selecting pathways that improve its prediction ability. We evaluated our method in simulation studies adopting 50 pathways for different sample sizes and genetic effect strengths. Additionally, we included an exemplary application of kernel boosting to a rheumatoid arthritis and a lung cancer dataset. Simulations indicate that kernel boosting outperforms the LKMT in certain genetic scenarios. Applications to GWAS data on rheumatoid arthritis and lung cancer resulted in sparse models which were based on pathways interpretable in a clinical sense. Kernel boosting is highly flexible in terms of considered variables and overcomes the problem of multiple testing. Additionally, it enables the prediction of clinical outcomes. Thus, kernel boosting constitutes a new, powerful tool in the analysis of GWAS data and towards the understanding of biological processes involved in disease susceptibility.
27821451 Phase I Clinical Trial Results of Auranofin, a Novel Antiparasitic Agent. 2017 Jan Under an NIH priority to identify new drugs to treat class B parasitic agents, we performed high-throughput screens, which identified the activity of auranofin (Ridaura) against Entamoeba histolytica and Giardia intestinalis, major causes of water- and foodborne outbreaks. Auranofin, an orally administered, gold (Au)-containing compound that was approved by the FDA in 1985 for treatment of rheumatoid arthritis, was effective in vitro and in vivo against E. histolytica and both metronidazole-sensitive and -resistant strains of Giardia We now report the results of an NIH-sponsored phase I trial to characterize the pharmacokinetics (PK) and safety of auranofin in healthy volunteers using modern techniques to measure gold levels. Subjects received orally 6 mg (p.o.) of auranofin daily, the recommended dose for rheumatoid arthritis, for 7 days and were followed for 126 days. Treatment-associated adverse events were reported by 47% of the subjects, but all were mild and resolved without treatment. The mean gold maximum concentration in plasma (C(max)) at day 7 was 0.312 μg/ml and the half-life (t(1/2)) 35 days, so steady-state blood levels would not be reached in short-term therapy. The highest concentration of gold, 13 μM (auranofin equivalent), or more than 25× the 50% inhibitory concentration (IC(50)) for E. histolytica and 4× that for Giardia, was in feces at 7 days. Modeling of higher doses (9 and 21 mg/day) was performed for systemic parasitic infections, and plasma gold levels of 0.4 to 1.0 μg/ml were reached after 14 days of treatment at 21 mg/day. This phase I trial supports the idea of the safety of auranofin and provides important PK data to support its potential use as a broad-spectrum antiparasitic drug. (This study has been registered at ClinicalTrials.gov under identifier NCT02089048.).
28948983 Scoring ultrasound synovitis in rheumatoid arthritis: a EULAR-OMERACT ultrasound taskforce 2017 OBJECTIVES: To develop a consensus-based ultrasound (US) definition and quantification system for synovitis in rheumatoid arthritis (RA). METHODS: A multistep, iterative approach was used to: (1) evaluate the baseline agreement on defining and scoring synovitis according to the usual practice of different sonographers, using both grey-scale (GS) (synovial hypertrophy (SH) and effusion) and power Doppler (PD), by reading static images and scanning patients with RA and (2) evaluate the influence of both the definition and acquisition technique on reliability followed by a Delphi exercise to obtain consensus definitions for synovitis, elementary components and scoring system. RESULTS: Baseline reliability was highly variable but better for static than dynamic images that were directly acquired and immediately scored. Using static images, intrareader and inter-reader reliability for scoring PD were excellent for both binary and semiquantitative (SQ) grading but GS showed greater variability for both scoring systems (κ ranges: -0.05 to 1 and 0.59 to 0.92, respectively). In patient-based exercise, both intraobserver and interobserver reliability were variable and the mean κ coefficients did not reach 0.50 for any of the components. The second step resulted in refinement of the preliminary Outcome Measures in Rheumatology synovitis definition by including the presence of both hypoechoic SH and PD signal and the development of a SQ severity score, depending on both the amount of PD and the volume and appearance of SH. CONCLUSION: A multistep consensus-based process has produced a standardised US definition and quantification system for RA synovitis including combined and individual SH and PD components. Further evaluation is required to understand its performance before application in clinical trials.
28814432 Minimal to no transfer of certolizumab pegol into breast milk: results from CRADLE, a pros 2017 Nov BACKGROUND: Women with chronic inflammatory diseases face uncertainty regarding the safety of biologics during breast feeding. CRADLE was the first industry-sponsored study to evaluate certolizumab pegol (CZP) concentrations in human breast milk and estimate average daily infant dose (ADID) of maternal CZP. METHODS: CRADLE (NCT02154425) was a pharmacokinetic study of lactating mothers receiving CZP. After ≥3 CZP doses, breast milk samples were collected across one dosing period (14 days for 200 mg every 2 weeks [Q2W]; 28 days for 400 mg every 4 weeks [Q4W]). Optimal analytical methods were developed to determine CZP and polyethylene glycol (PEG) levels in breast milk. ADID and relative infant dose (RID) were estimated. Safety events in mothers and infants were assessed. RESULTS: 19 CZP-treated mothers were screened; 17 entered the sampling period: 16 on 200 mg Q2W, 1 on 400 mg Q4W. 77/137 (56%) breast milk samples had no measurable CZP. For 4/17 mothers, all samples were below the lower limit of quantification (LLOQ). Estimated ADID was 0-0.0104 mg/kg/day; median RID: 0.15%. PEG was undetectable in 134/137 samples (results could not be determined in three samples). Infants of CZP-exposed mothers had a safety profile consistent with that of unexposed similar-age infants. CONCLUSION: When quantifiable, CZP concentrations were <3× LLOQ (<1% plasma concentration observed with therapeutic dose), indicating no/minimal CZP transfer from plasma to breast milk. RID was 0.15% of maternal dose; <10% is considered unlikely to be of clinical concern. No PEG transfer was observed. CZP absorption by infants via breast milk is unlikely due to its low oral bioavailability and Fc--free molecular structure. These findings are reassuring and support continuation of CZP treatment during breast feeding. TRIAL REGISTRATION NUMBER: NCT02154425; Results.
29105349 Cost-effectiveness of bisphosphonates for prevention of fracture related to glucocorticoid 2018 Mar INTRODUCTION: Glucocorticoid therapy is associated with an appreciable risk of bone loss leading to fractures that require expensive treatments. This study aimed to evaluate the cost-effectiveness of bisphosphonates for prevention of hip fracture in glucocorticoid-induced osteoporosis (GIOP) in Malaysia. METHOD: Retrospective data were collected from GIOP patients referred to the Universiti Kebangsaan Malaysia Medical Centre. Fracture events and direct medical costs were compared between bisphosphonates and calcium/vitamin D combination. RESULTS: Fracture events were reported in 28 out of 93 included patients, with hip and vertebral fractures representing 42.9% and 35.7%, respectively. Overall, the use of bisphosphonates could not be considered cost-effective for treatment of all GIOP patients. The presence of certain fracture risk factors was able to modify the cost-effectiveness of bisphosphonates. Bisphosphonates was considered cost-effective if started in patients more than 60 years old. However, the use of bisphosphonates was not cost-effective in GIOP patients with secondary osteoporosis. The incremental cost-effectiveness ratios (ICER) of bisphosphonates in patients with risk factors of previous fracture or rheumatoid arthritis were Malaysian Ringgits (MYR) 108 603.40 and MYR 25 699.21, respectively. CONCLUSION: Fracture risk factors of age, previous fracture, rheumatoid arthritis and secondary osteoporosis may modify the cost-effectiveness outcomes of bisphosphonates. Bisphosphonates would be considered cost-effective in patients more than 60 years old as compared to calcium/vitamin D treatments. Further evaluation of the impact of fracture risk factors in larger populations would provide more precise information to better assist rational and economical use of anti-osteoporosis treatment in GIOP patients.
29179258 Increased risk of autoimmune disorders in infertile men: analysis of US claims data. 2018 Jan Aberrations in reproductive fitness may be a harbinger of medical diseases in men. Existing data suggest that female infertility is associated with autoimmune disorders; however, this has not been examined in men. As immune surveillance and hormonal factors can impact male fertility and autoimmunity, we sought to determine the association between male infertility and incident autoimmune disorders. We analyzed subjects from the Truven Health MarketScan claims database from 2001 to 2008. Infertile men were identified through diagnosis and treatment codes. We examined the most common immune disorders, which were identified by ICD9 diagnosis codes. Men diagnosed with an immune disorder at baseline or within 1 year of follow-up were excluded. Infertile men were compared to vasectomized men (i.e., men who are likely fertile) and to age-matched control (10 : 1) group using Cox regression analysis. A total of 33,077 infertile men (mean age of 33 years), 77,693 vasectomized men (mean age 35), and 330,770 age-matched control men (mean age 33) were assembled with a total follow-up of 1.49 M person-years. Overall, immune disorders were rare in the group with the individual conditions occurring in <0.1% of men. However, infertile men displayed the highest risk of many conditions. Infertile men had a higher risk of developing rheumatoid arthritis compared to both vasectomized men (HR 1.56, 95% CI 1.19-2.05) and age-matched controls (HR 1.29, 95% CI 1.02-1.62). Additionally, this higher risk was seen in general immune disorders (under which systemic lupus erythematosus is categorized) compared to vasectomized men (HR 3.11, 95% CI 2.00-4.86) and age-matched men (HR 2.12, 95% CI 1.52-2.96). This same risk trend was seen in psoriasis, when compared to vasectomized men (HR 1.28, 95% CI 1.09-1.50) and age-matched controls (HR 1.20, 95% CI 1.04-1.37). A similar trend was seen in the analysis comparing infertile men and vasectomized men in developing multiple sclerosis (HR 1.91, 95% CI 1.10-3.31) and Grave's disease (HR 1.46, 95% CI 1.10-1.92), as well as the higher risk of infertile men compared to the age-matched group at developing thyroiditis (HR 1.60, 95% CI 1.02-2.52). The current analysis shows that infertile men have a higher risk of developing certain autoimmune disorders in the years following an infertility evaluation. Specifically, infertile men had higher rates of developing rheumatoid arthritis, multiple sclerosis, psoriasis, thyroiditis, and Grave's disease. Given these findings, further research should focus on confirmation of these associations and elucidation of the pathways between fertility and immunity.
29116541 A cross-sectional study of vitamin D levels in a large cohort of patients with rheumatic d 2018 Mar The objective of this study is to examine 25-hydroxyvitamin D [25(OH)D] (D-25) levels and associations with patient- and disease-related factors in rheumatic diseases. This is a register-based study of D-25 levels in adult patients seen at the Central Finland Hospital rheumatology clinic (January 2011-April 2015). Demographic, clinical, laboratory, and patient-reported outcomes (PROs) were collected as part of the normal infrastructure of the outpatient clinic and examined for their association with D-25 level. Statistical analysis included descriptive statistics and univariable and multivariable regression analyses adjusting for age and gender. D-25 was measured in 3203 patients (age range 15-91 years, mean 54; 68% female) with diagnoses including RA (n = 1386), unspecified arthralgia/myalgia (n = 413), and connective tissues diseases (n = 213). The overall D-25 mean (SD) level was 78 (31) and median (IQR) 75 (55, 97). At baseline, 17.8% had D-25 deficiency, and only 1.6% severe deficiency  (< 25 nmol/l); 34%/49% had sufficient/optimal D-25 levels. Higher D-25 levels were associated with older age, lower BMI, and regular exercise (all p < 0.001) among other factors. In multivariable analyses, younger age, non-white background, higher BMI, smoking, less frequent exercise (p < 0.001), and first visit to the clinic (p = 0.033) remained significantly associated with D-25 deficiency. Among those with sub-optimal D-25 levels, 64% had improved to sufficient/optimal levels after a median (IQR) of 13 (7.8, 22) months. The proportion of patients with D-25 deficiency in this study was generally low. Older patients had considerably higher D-25 levels compared to younger patients. Lower physical exercise and higher BMI were associated with higher risk of deficiency. The study supports the benefit of strategies to help minimize the risk of D-25 deficiency.
29183861 Bilateral striopallidodentate calcinosis associated with Sjögren's syndrome and IgDλ mon 2018 Mar We presented the first case of bilateral striopallidodentate calcinosis secondary to Sjögren's syndrome. Further consideration should be given to the association between Sjögren's syndrome and bilateral striopallidodentate calcinosis, because Sjögren's syndrome is latent, but more frequent than other autoimmune diseases.
29148412 Psychological comorbidities associated with subclinical atherosclerosis in Greek patients 2018 May OBJECTIVES: Impaired sleep and psychological disorders are increasingly recognised as prevalent comorbidities in patients with primary Sjögren's syndrome (pSS), as well as important contributors of atherosclerosis in the general population. In the current study we sought to explore a potential role of psychological comorbidities in the pronounced atherosclerotic risk of pSS patients. METHODS: Fifty-nine pSS patients fulfilling the ACR/EULAR criteria completed specific validated questionnaires assessing fatigue, depression, anxiety and sleep disturbances. Clinical, laboratory and histopathological characteristics together with traditional risk factors for atherosclerosis were documented in all enrolled patients. Subclinical atherosclerosis defined either as carotid and/or femoral plaque formation or increased intima media thickness (IMT) levels were assessed by Doppler ultrasound. Univariate and multivariate analysis were performed. RESULTS: Plaque formation and high IMT levels were detected by ultrasound in 41(69.5%) out of the 59 pSS patients. In univariate analysis, age and higher triglyceride serum levels were associated with both plaque formation and high IMT levels. Hypertension was associated only with high IMT levels. While increased rates of both state anxiety and impaired sleep were detected in pSS patients with plaque formation in a univariate model, only impaired sleep proved to be independently associated with plaque formation among pSS patients (OR = 4.2, 95% CI =1.1-15.6, p=0.03). CONCLUSIONS: This is the first study showing impaired sleep to confer a significantly higher risk of subclinical atherosclerosis in patients with pSS. Clinicians should take psychological disturbances into account when trying to assess and manage the cardiovascular disease risk of pSS patients.
28080954 Sjögren Syndrome and Pregnancy: A Literature Review. 2017 OBJECTIVES: Autoimmune diseases do not impair fertility, and women with autoimmune diseases who become pregnant are likely to experience more complicated pregnancies than are women without the disease. Pregnancies complicated by these disorders have a high clinical impact on both the pregnancy and the disease. The effect of autoimmune disease on pregnancy differs according to the type of maternal disease, disease activity, severity of organ damage, antibody profile, and drug treatment. Sjögren syndrome is an autoimmune disease with a high prevalence of anti-SS-A (anti-Ro) and anti-SS-B (anti-La) antibodies. Anti-SS-A antibodies are associated with congenital heart block. Data on pregnancy outcomes in primary Sjögren syndrome are scarce. METHODS: We performed a review of the literature regarding pregnancy outcomes in women with Sjögren syndrome. RESULTS: Women with Sjögren syndrome are likely to experience more complications during pregnancy than women without an autoimmune disease. Studies show a high incidence of poor fetal outcomes for these patients. CONCLUSION: Women with Sjögren syndrome require prenatal counseling explaining the risks involved and the need to control the disease well before conception. High-risk pregnancies can be optimally managed by a multidisciplinary team.
28587293 Pathological Analysis of Ocular Lesions in a Murine Model of Sjögren's Syndrome. 2017 Jun 6 Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by severe inflammation of exocrine glands such as the salivary and lacrimal glands. When it affects the lacrimal glands, many patients experience keratoconjunctivitis due to severely dry eyes. This study investigated the pathological and immunological characteristics of ocular lesions in a mouse model of SS. Corneal epithelial injury and hyperplasia were confirmed pathologically. The number of conjunctival mucin-producing goblet cells was significantly decreased in the SS model mice compared with control mice. Expression levels of transforming growth factor (TGF)-β, interleukin (IL)-6, tumor necrosis factor (TNF)-α, and C-X-C motif chemokine (CXCL) 12 were significantly higher in the corneal epithelium of the SS model mice than in control mice. Inflammatory lesions were observed in the Harderian, intraorbital, and extraorbital lacrimal glands in the SS model mice, suggesting that the ocular glands were targeted by an autoimmune response. The lacrimal glands of the SS model mice were infiltrated by cluster of differentiation (CD)4⁺ T cells. Real-time reverse transcription-polymerase chain reaction (RT-PCR) revealed significantly increased mRNA expression of TNF-α, TGF-β, CXCL9, and lysozyme in the extraorbital lacrimal glands of the SS model mice compared with control mice. These results add to the understanding of the complex pathogenesis of SS and may facilitate development of new therapeutic strategies.
27943374 Expression of Toll-Like Receptors in Peripheral Blood Mononuclear Cells of Patients with P 2017 Mar Toll-like receptors (TLRs) are pattern recognition receptors important for the detection of pathogen-associated molecular patterns. They are localized on cellular membranes, on either the cell surface or the endosomes. Primary Sjögren's syndrome (pSS) is a systemic rheumatic autoimmune disease characterized by lymphocytic infiltrations in exocrine glands resulting in dryness in eyes and mouth. In a majority of patients, autoantibodies against Ro/SSA and/or La/SSB are present. Here we analysed mRNA levels of TLR1-10 and protein expression levels of most of them in human peripheral blood mononuclear cells from 20 patients with pSS and 20 healthy controls. Patients with pSS showed significantly higher mRNA levels of TLR8 than controls, while transcript levels of TLR9 were significantly lower. At the protein level, patients with pSS expressed significantly less TLR5 and significantly more TLR7 compared with healthy controls. TLR7 and 8 are encoded by genes localized on the X chromosome, which is especially interesting regarding the gender imbalance of pSS. The differential expression of various TLR in PBMC of patients with pSS might contribute to an altered recognition of nucleic acids, eventually resulting in the development of autoimmune disease.