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ID PMID Title PublicationDate abstract
30632148 FoxP3(+) CXCR5(+) CD4(+) T cell frequencies are increased in peripheral blood of patients 2019 Mar We recently explored the expression of CXCR5 on T and B cells from peripheral blood of patients with primary Sjögren's syndrome (SS). Here we investigated the frequency of CD25(+) FoxP3(+) CD4(+) regulatory T cells (T(regs) ) among CXCR5(+) CD4(+) follicular cells in the same cohort of patients. We confirm that the frequency of T(regs) among follicular T cells is increased in SS patients and also provide novel data showing an increased frequency of PD-1 expressing cells among CXCR5(+) FoxP3(+) CD4(+) T cells.
31529714 Telomere erosion in Sjögren's syndrome: A multi-tissue comparative analysis. 2020 Jan BACKGROUND: Acinar progenitor cells within salivary glands have decreased regenerative capacity and exhibit shorter telomeres in primary Sjögren's syndrome (pSS) patients. We investigated whether DNA of saliva, PBMCs, and labial salivary gland (LSG) biopsy tissue have shorter telomeres in pSS compared to controls. mRNA expression of genes associated with pSS pathogenesis (ETS1, LEF1, and MMP9), telomere DNA damage response (ATM), senescence (CDKN2A), telomerase inhibition (IFN-y, TGFβ1), and the shelterin complex (TPP1, POT1) were assessed in LSG tissue by qRT-PCR to examine potential defects in telomere maintenance. METHODS: Relative telomere length in DNA of saliva, PBMCs, and LSGs from non-pSS sicca and pSS patients was measured using qPCR. Saliva DNA telomere length was further compared to healthy controls. Expression of genes affecting telomere maintenance was analyzed in LSGs using qRT-PCR. RESULTS: Primary Sjögren's syndrome patients have shorter telomeres in saliva DNA (n = 21) than healthy controls (n = 27) (P = .0035). ATM mRNA expression was higher in pSS LSG tissue (n = 16) vs non-pSS sicca patients (n = 13) (P = .0283) and strongly correlated with LEF1, TPP1, and POT1 (P < .01, r > 0.6). CONCLUSIONS: Patients with pSS exhibited significant telomere erosion in saliva DNA. Overexpression of ATM in LSGs could represent a compensatory response to telomere shortening. The role of LEF1 in telomere erosion remains to be elucidated.
31872367 Challenges in Treatment of Primary Sjögren's Syndrome and Opportunities for Chinese Medic 2020 Jul Primary Sjögren's syndrome is a chronic autoimmune disease that can lead to systemic manifestations. At present, immunomodulatory agents have not shown good efficacy, many patients in China seek Chinese medicine treatment. Chinese medicine can comprehensively improve the symptoms of patients through Chinese pattern diagnosis and individualized treatment. Fundamental researches are providing scientific bases for the therapeutic effect of Chinese medicine. Professional Chinese medicine treatment can be integrated into the conventional management of primary Sjögren's syndrome.
31848493 [Clinical characteristics and treatment outcomes of macrophage activation syndrome in adul 2019 Dec 18 OBJECTIVE: To described the clinical and laboratory features and outcome of 67 macrophage activation syndrome (MAS). METHODS: A total of 67 MAS patients from three centers from January 2007 to December 2017 were enrolled. Clinical and laboratory features, and response to therapy were analyzed. Predictive factors for remission and survival were explored. RESULTS: We identified a mean age of (36.1±16.3) years at diagnosis of MAS and a median connective tissue disease (CTD) duration of 8 months prior to MAS development. Among 67 MAS patients identified, underlying diseases included adult-onset Still's disease (AOSD) in 56.7% and systemic lupus erythematosus (SLE) in 30.0%. Fever and splenomegaly were found in 100.0% and 82.1% of the patients, respectively. Ferritinemia and elevation of serum soluble interleukin-2 receptor was seen in 100.0% and 93.2% of the patients. Serum levels of alanine aminotransferase, D-dimer, ferritin and C reactive protein were significantly higher in MAS associated with the AOSD patients than in MAS associated with the SLE patients. A significant decrease of erythrocyte sedimentation rate was found in MAS associated with AOSD, as compared with MAS associated with SLE. The most commonly used therapy was corticosteroids, which were initially administered in 100.0% of the patients. Intravenous immunoglobulin (IVIG) was administered in 91.0%, cyclosporine A in 64.2%, and etoposide in 46.3% of the patients, respectively. The induction therapy yielded a complete remission (CR) at the end of week 8 in 47.8% of the MAS patients. The overall mortality rate at the end of week 16 was 22.4%. The median serum levels of gamma-glutamyltransferase, alkaline phosphatase, total bilirubin and direct bilirubin were significantly lower in the patients who achieved complete remission at the end of week 8 than in those who did not, and splenomegaly was significantly less frequent (71.9% vs.91.4%, P=0.037). Both the mean age at diagnosis of MAS and the mean age at diagnosis of underlying CTD of the deceased patients were elder than those of the survived population (P=0.014 and P=0.017, respectively). The platelet count was significantly less in the deceased population as compared with the living population (P=0.018). No addition of cyclosporine A (P=0.004) was identified as risk factors associated with death in Logistic regression analysis. CONCLUSION: MAS secondary to connective tissue disease is most common with AOSD and SLE. In terms of laboratory findings, there were considerable differences between the patients with underlying SLE and those with AOSD. Advanced age and low platelet counts are significant predictive factors for death, while treatment with cyclosporine may reduce the risk.
30827571 Dental implants in patients with Sjögren's syndrome: a case series and a systematic revie 2019 Sep The purpose of this study was to assess the clinical outcomes of dental implants in patients with Sjögren's syndrome (SS). The study consisted of two parts: report of a case series and a systematic review of the literature. The results of the clinical series revealed that 19 patients received 107 implants and were followed for a mean of 125months. Two patients lost three implants (failure rate 2.8%, 3/107). At the last follow-up, there was a mean marginal bone loss (MBL) of -2.190±1.384 mm; estimated MBL after 30 years was 4.39mm. The review identified 18 studies, resulting in 19 studies for analysis including the present clinical series. A total of 712 implants were placed in 186 patients; 705 implants were followed up for a mean of 72.5 months (failure rate 4.1%, 29/705; failed at a mean time of 12.9±31.7months). The probability of failure was 2.8% (95% confidence interval 1.6-4.1%). Primary SS patients had a lower implant failure rate (2.5%, 3/118) than secondary SS patients (6.5%, 12/184). In conclusion, dental implants should be considered by dentists as a viable treatment option for patients with SS, as the failure rate is fairly low. SS patients may, however, present a higher MBL around implants than patients from the general population.
31766755 Osteoporosis in Rheumatic Diseases. 2019 Nov 22 Osteoporosis is a chronic disease characterized by an increased risk of fragility fracture. Patients affected by rheumatic diseases are at greater risk of developing osteoporosis. The purpose of the present review is to discuss the pathogenesis, epidemiology, and treatment of osteoporosis in patients affected by rheumatic diseases with special focus for rheumatoid arthritis, psoriatic arthritis, spondyloarthritis, systemic lupus erythematosus, systemic sclerosis, vasculitides, Sjogren syndrome, and crystal-induced arthritis.
31228805 In situ hexagonal liquid crystal for intra-articular delivery of sinomenine hydrochloride. 2019 Sep The aim of this study was to investigate the release behaviors of sinomenine hydrochloride loaded via in situ hexagonal liquid crystal (ISH), and its potential to improve the local bioavailability in knee joints of sinomenine hydrochloride (SMH) after intra-articular administration. The ISH was prepared by a liquid precursor mixture containing phytantriol (PT), Vitamin E acetate (VEA), ethanol (ET), and water. The in vitro release profiles revealed a sustained release of SMH from the optimized ISH formula (PT/VEA/ET/water, 60.8:3.2:16.0:20.0, w/w/w/w), which was selected for the in vivo pharmacokinetics and preliminary pharmacodynamics studies. In both healthy and adjuvant-induced arthritis (AA) rats, the SMH loaded ISH showed significantly smaller SMH AUC(0-∞) in plasma (P <  0.01), and higher SMH concentration in synoviums (2˜168 h) than that of SMH solution, indicating that the ISH significantly reduced the leakage of SMH into systemic circulation. The t(1/2α) of SMH loaded ISH in the knee joints of AA rats, was longer (13.42 h) than that of healthy rats (1.34 h) (P < 0.05), most likely that in vivo drug release behavior of SMH loaded ISH was affected by the physiological environment of the joint. It was found that the SMH loaded ISH could benefit AA-rats by suppressing the level of IL-1β in comparison to SMH solutions. The results of the histopathology of knee joints in AA rats displayed that the SMH loaded ISH might be suitable for the development of treatment strategies for rheumatoid arthritis diseases.
31325437 PSTPIP2 attenuates joint damage and suppresses inflammation in adjuvant-induced arthritis. 2019 Sep 15 Proline-serine-threonine-phosphatase-interacting protein 2 (PSTPIP2) is related to inflammation. In this study, we investigated the function of PSTPIP2 in adjuvant-induced arthritis (AIA) by using adeno-associated virus (AAV) to overexpress PSTPIP2 in rat. AIA rats were developed by injecting Lewis rats with complete Freund's adjuvant (CFA) on day 0. AAV-empty or AAV-PSTPIP2, or PBS was administered intraarticularly into each knee joint on day 8 postinduction. All animals were killed at day 18 after adjuvant injection. WB was used to detect the expression of PSTPIP2 in rat synovial tissues. Fluorescence microscopy showed the transduction efficiency in synovial tissue. The morphology of arthritic joints was examined by HE, safranin O/fast green, or Toluidine blue staining. The bone destruction was examined via X-ray and micro-CT analysis. Immunohistochemical analysis or TRAP staining were used to investigate the role of PSTPIP2 in osteoclasts and the expression of PSTPIP2 in synovial tissue. RT-qPCR and ELISA were used to examine the expression of pro-inflammatory cytokines in synovial tissue or serum. AIA rats were found to have decreased PSTPIP2 expression and AIA-associated bone loss and inflammatory infiltration. We showed that administration of AAV-PSTPIP2 before arthritis onset significantly reduces the severity of AIA. PSTPIP2 was highly expressed in synovial cells. In addition, inflammatory responses and the number of osteoclasts were reduced with AAV-PSTPIP2 treatment. These findings demonstrate that PSTPIP2 may improve the severity of AIA by inhibiting the function of fibroblast-like synoviocytes, suppressing inflammation and reducing the number of osteoclasts.
30922375 Consequences of bariatric surgery on outcomes in rheumatic diseases. 2019 Mar 28 Obesity is associated with numerous comorbidities including some rheumatic conditions. Through adipose-derived inflammation, obesity has been shown to induce increased initiation, progression, and worse responses on outcomes of rheumatic diseases. Bariatric surgery is being increasingly used thanks to its positive effects on major comorbidities such as type 2 diabetes mellitus and hypertension. Consequently, surgically induced weight and adipose tissue losses might play a role in the course of rheumatic conditions. The present narrative literature review aims to provide rheumatologists with an update on both the positive and negative effects of bariatric surgery on the rheumatic outcomes reported in the literature. Current evidence seems to show improved outcomes in obese populations with rheumatic disorders after bariatric surgery. However, rigorous prospective controlled studies with long follow-up are needed. Bariatric procedures have deleterious effects on bone and are associated with an increased risk of fractures.
31580326 Autoimmune diseases in Turner syndrome: an overview. 2019 Sep 6 Turner syndrome (TS) results from a sex-chromosomal anomaly characterized by presence of one normal X chromosome and the loss of the second X-chromosome in phenotypic females. Autoimmunity has been recognized as one of the more prominent characteristics of TS. The risk of autoimmune diseases in patients with TS is approximately twice as high as in the general female population. The spectrum includes, Hashimoto's thyroiditis, coeliac disease (CD), type 1 diabetes (T1DM), alopecia areata, inflammatory bowel disease, juvenile rheumatoid arthritis and some cutaneous disorders as vitiligo and Halo nevus. This review will address the autoimmune disorders associated with TS, their pathophysiologic mechanisms and clinical characteristics.
31807958 Inflammation and the Central Nervous System in Inflammatory Rheumatic Disease. 2019 Dec 5 PURPOSE OF REVIEW: To review how peripheral inflammation in rheumatic disease influences the central nervous system. We consider recent studies of rheumatic disease that employ functional and structural neuroimaging in the context of inflammation, as well as recent studies considering how immunosuppressive therapy is associated with changes in brain function and structure. RECENT FINDINGS: The most compelling evidence thus far comes from studies of rheumatoid arthritis and indicates that higher levels of inflammation are associated with changes in cognitive, affective, and pain-processing brain regions, some of which may be rectified by anti-inflammatory treatment. Comorbid symptoms such as widespread pain and fatigue may also be associated with these changes. Inflammation may be associated with compensatory activation of brain regions to offset structural changes. This emerging line of evidence suggests that communication between the brain and immune system are an important and underappreciated aspect of inflammatory rheumatic disease.
31777782 Association of Arthritis Onset with Influenza: Analysis of the Canadian Early Inflammatory 2019 Mar OBJECTIVE: To evaluate seasonal patterns of early inflammatory arthritis (IA) onset and potential associations with IA symptom onset. METHODS: The Canadian Early Arthritis Cohort (CATCH) is an inception cohort study of adults with early (12 months or less) IA. We used patient reports of symptom onset as a proxy of IA onset and examined the seasonal distribution of IA onset over 10 years. Influenza time series was based on laboratory-confirmed influenza A and B from the Canadian FluWatch surveillance from 2010-2016. Bivariate analysis of influenza and IA was performed using cross-correlations with different time lags and Poisson regression. IA and influenza were recorded as monthly total frequencies. RESULTS: Of 2519 IA patients, 88% had confirmed rheumatoid arthritis (RA). Significantly, more IA onsets occurred in winter compared with other seasons (P = 0.03); although IA onset was more frequent in January, the difference between months was not statistically significant. Compared to months with the lowest influenza rates, months with the highest influenza rates had a statistically significant, but trivial, increase of 0.003% in the incidence of IA (incidence rate ratio (95% confidence interval): 1.00003 (1.00005; 1.000053), P = 0.02). CONCLUSION: Although IA symptom onset occurs more frequently in winter, we found that flu outbreaks were not associated with a meaningful increase in IA symptom onset in a large, well-characterized cohort of Canadian adults over 6 years.
33086964 Assessing an alpha-defensin lateral flow device for diagnosing septic arthritis: reporting 2020 Jan Alpha-defensin (αD), an antimicrobial peptide released by neutrophils in response to bacterial pathogens, was proposed as a novel diagnostic biomarker in synovial fluid. Several reports have shown that αD can serve as a reliable biomarker in the diagnosis of periprosthetic joint infection (PJI). We assessed whether αD could also serve to diagnosis of septic arthritis, a similarly difficult to diagnose PJI. To our knowledge, besides PJI, few reports exist assessing the utility of αD for septic arthritis. We have attempted to diagnose several cases of suspected septic arthritis using the Synovasure(®) αD detection lateral flow device. We report a false-positive case and a false-negative case. The false-negative case we experienced was caused by Staphylococcus capitis, which is coagulase-negative, and possibly represents a low virulence micro-organism infection. The false-positive case was ultimately diagnosed as seronegative rheumatoid arthritis and possessed calcium pyrophosphate depositions. False positives have been suggested to occur in conditions where neutrophils are mobilised. As for PJI, in cases where diagnosis is difficult, αD can be an additional diagnostic indicator. However, making a definitive diagnosis using the αD lateral flow device alone was found to be difficult. The utility of αD in assessing septic arthritis is inconclusive; therefore, larger prospective clinical studies should be considered for a better assessment.
31564885 Clinical evaluation of the safety, efficacy and tolerability of sarilumab in the treatment 2019 Rheumatoid arthritis (RA) is an autoimmune disease that is characterised by synovial inflammation and progressive joint disorder with significant pain and stiffness, which lead to functional disability and systemic complications if left untreated. Although methotrexate (MTX) is the cornerstone in the RA therapy, it is ineffective or intolerable in up to 50% of patients. In addition, tumour necrosis factor (TNF) inhibitors which are regarded as the standard of care for those patients, have not been proven a panacea creating a therapeutic gap. In this direction, other cytokines such as the interleukin (IL)-6 in combination with MTX or as monotherapy have been approved. Sarilumab has already been approved for the treatment of moderate to severe RA, but more studies are on their way including polymyalgia rheumatica, giant cell arteritis, juvenile idiopathic arthritis, and indolent systemic mastocytosis. On the other hand, a study was prematurely discontinued after approximately 1.5 years, when the ankylosing spondylitis development program was discontinued due to lack of efficacy. Regarding safety, efficacy and tolerability of the molecule, three pivotal clinical trials have established sarilumab as one of the safe and efficacious choices for the treatment of RA (mobility, target and monarch trials). Significant decreases in progression of structural damage have been demonstrated. Infections and neutropenia are two of the most common adverse events. Sarilumab is beyond any doubt another molecule that can be added to the clinicians' armamentarium for the treatment of patients with moderate to severe RA with a good safety and efficacy profile.
31355342 New onset or exacerbation of uveitis with infliximab: paradoxical effects? 2019 OBJECTIVE: To report four cases of new onset or exacerbation of uveitis following administration of infliximab. METHODS: This retrospective observational case series includes four patients who developed new onset or exacerbation of uveitis paradoxically during infliximab treatment. RESULTS: Four patients were assessed, including three women, with a mean age of 33 (14-84) years. Infliximab was introduced for the treatment of scleritis associated with rheumatoid arthritis (two cases), chronic anterior uveitis associated with juvenile idiopathic arthritis (JIA) (one case) and Crohn's disease (one case). Anterior scleritis associated with rheumatoid arthritis successfully improved following infliximab administration; however, macular oedema or dense vitritis paradoxically developed in two cases. In one case, infliximab was switched to tocilizumab. In another case, infliximab was discontinued, and additional corticosteroids and immunosuppressive medications were added. In one patient with JIA, new-onset macular oedema and exacerbation of anterior uveitis were observed during infliximab treatment, so the patient was switched to adalimumab. In the patient with Crohn's disease treated with infliximab, severe vasculitis and macular oedema occurred, requiring intravitreal triamcinolone injection. The patient was switched to adalimumab. Given that these reactions were paradoxical effects of infliximab, infliximab treatment was discontinued in all cases, and additional corticosteroids or immunosuppressive medications were added. All cases remained free of ocular inflammation at the last visit. CONCLUSION: Uveitis rarely occurs de novo or is exacerbated during infliximab treatment. Cessation of infliximab led to resolution of this paradoxical adverse effect.
35382152 Inflammatory arthritis in systemic sclerosis: What to do? 2019 Feb Musculoskeletal involvement, including arthritis and tendinopathy, is a common and important determinant of disability and impaired quality of life in systemic sclerosis. However, the treatment of arthritis in systemic sclerosis has not been studied as a primary outcome in randomized controlled trials, and arthritis-specific outcome measures for systemic sclerosis have not been sufficiently validated to date. Rheumatologists caring for patients with systemic sclerosis must address these complaints regularly despite the fact that the level of evidence for the treatment of systemic sclerosis-related inflammatory arthritis is limited. Consensus statements, based on treatments for related musculoskeletal aspects of rheumatoid arthritis, systemic lupus erythematosus, and other autoimmune diseases, support the use of methotrexate and hydroxychloroquine. Newer biologics, which have efficacy in the treatment of other autoimmune conditions, may show promise in the treatment of arthritis in systemic sclerosis. In this article, we review the current literature on the assessment and treatment of systemic sclerosis arthritis in order to address management considerations.
31763801 Osteoclasts in Health and Disease. 2019 Dec Osteoclasts are multinucleated, giant cells originating from myeloid hematopoetic stem cells. These are the only cells in nature which can resorb bone. Differentiation of mononucleated osteoclast progenitor cells requires stimulation with M-CSF (macrophage colony-stimulating factor) for the cells to proliferate and survive and with RANKL (receptor activator of nuclear factor kappa B ligand) for differentiation along the osteoclastic lineage to cells which eventually fuse to the mature, multinucleated osteoclasts. Therefore, most hormones and cytokines stimulating osteoclastogenesis do so indirectly by regulating the expression in osteoblasts of RANKL and its inhibitory decoy receptor OPG. Antibodies neutralizing RANKL is a common therapy to inhibit excessive osteoclast formation in diseases such as osteoporosis and malignant tumors with skeletal metastasis. Mature osteoclasts resorb bone by stimulating acid release into the resorption lacunae, followed by proteolytic degradation of bone matrix proteins. Loss-of-function mutations of proteins involved in acidification and proteolysis cause osteopetrosis, a disease with sclerotic bone due to non-functional osteoclasts. Osteoclasts are important for a healthy skeleton by removing damaged bone during remodeling of the skeleton, but are also important for modeling of bone, calcium homeostasis and tooth eruption, and possibly also for glucose and fat metabolism. Loss of bone in inflammatory disease, metastasizing tumors and osteoporosis is due to increased RANKL expression and enhanced osteoclast formation. The present overview aims to summarize how osteoclasts are formed and resorb bone in health and disease.
31161663 Epidemiology of uveitis in a region of southern Sweden. 2020 Feb PURPOSE: To analyse the distribution and treatment of uveitis in a region of southern Sweden and compare the results with previously reported European data. METHODS: Anonymized data for all individuals in the region with an ICD-10 diagnosis that indicated uveitis between 2013 and 2017 were extracted from a computerized healthcare register. RESULTS: In total, 2483 patients were diagnosed with uveitis during 2013-2017. Anterior uveitis was diagnosed in 93%, intermediate in 1%, posterior in 5% and panuveitis in 1% of cases. An associated diagnosis was found in 14%, and the five most common associated diseases were herpes simplex/zoster (4.9%), inflammatory bowel disease (2.2%), rheumatic arthritis (1.9%), ankylosing spondylitis (1.8%) and sarcoidosis (1.8%). Systemic treatment was used in 14% of the cases. The period prevalence of uveitis was 700 cases per 100 000 individuals, and the yearly incidence was estimated to 108 cases/year/100 000 individuals. CONCLUSIONS: Compared with studies from referral clinics, this community-based study had a large proportion of anterior uveitis (93%) and uveitis without associated diagnosis (86%). Uveitis was also much more common among elderly than shown in previous research. The distribution of possible associated diagnosis conformed to several previous European studies.
31134204 Clinical Applications of Synovial Biopsy. 2019 The synovial tissue is a primary target of multiple diseases characterized by different pathogenic mechanisms, including infective, deposition, neoplastic, and chronic immune-inflammatory pathologies. Synovial biopsy can have a relevant role in differential diagnosis of specific conditions in clinical practice, although its exploitation remains relatively limited. In particular, no validated synovial-tissue-derived biomarkers are currently available in the clinic to aid in the diagnosis and management in most frequent forms of chronic inflammatory arthropathies, namely rheumatoid arthritis (RA) and the spondyloarthritides (SpA). In this brief review, we will discuss the current spectrum of clinical applications of synovial biopsy in routine rheumatologic care and will provide an analysis of the perspectives for its potential exploitation in patients with chronic inflammatory arthritides.
30389690 Tolerising cellular therapies: what is their promise for autoimmune disease? 2019 Mar The current management of autoimmunity involves the administration of immunosuppressive drugs coupled to symptomatic and functional interventions such as anti-inflammatory therapies and hormone replacement. Given the chronic nature of autoimmunity, however, the ideal therapeutic strategy would be to reinduce self-tolerance before significant tissue damage has accrued. Defects in, or defective regulation of, key immune cells such as regulatory T cells have been documented in several types of human autoimmunity. Consequently, it has been suggested that the administration of ex vivo generated, tolerogenic immune cell populations could provide a tractable therapeutic strategy. Several potentially tolerogenic cellular therapies have been developed in recent years; concurrent advances in cell manufacturing technologies promise scalable, affordable interventions if safety and efficacy can be demonstrated. These therapies include mesenchymal stromal cells, tolerogenic dendritic cells and regulatory T cells. Each has advantages and disadvantages, particularly in terms of the requirement for a bespoke versus an 'off-the-shelf' treatment but also their suitability in particular clinical scenarios. In this review, we examine the current evidence for these three types of cellular therapy, in the context of a broader discussion around potential development pathway(s) and their likely future role. A brief overview of preclinical data is followed by a comprehensive discussion of human data.