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ID PMID Title PublicationDate abstract
28042126 B Cell Depletion Therapy Normalizes Circulating Follicular Th Cells in Primary Sjögren Sy 2017 Jan OBJECTIVE: To assess the effect of B cell depletion therapy on effector CD4+ T cell homeostasis and its relation to objective measures of disease activity in patients with primary Sjögren syndrome (pSS). METHODS: Twenty-four patients with pSS treated with rituximab (RTX) and 24 healthy controls (HC) were included. Frequencies of circulating effector CD4+ T cell subsets were examined by flow cytometry at baseline and 16, 24, 36, and 48 weeks after the first RTX infusion. Th1, Th2, follicular Th (TFH), and Th17 cells were discerned based on surface marker expression patterns. Additionally, intracellular cytokine staining was performed for interferon-γ, interleukin (IL)-4, IL-21, and IL-17 and serum levels of these cytokines were analyzed. RESULTS: In patients with pSS, frequencies of circulating TFH cells and Th17 cells were increased at baseline compared with HC, whereas frequencies of Th1 and Th2 cells were unchanged. B cell depletion therapy resulted in a pronounced decrease in circulating TFH cells, whereas Th17 cells were only slightly lowered. Frequencies of IL-21-producing and IL-17-producing CD4+ T cells and serum levels of IL-21 and IL-17 were also reduced. Importantly, the decrease in circulating TFH cells was associated with lower systemic disease activity over time, as measured by the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index scores and serum IgG levels. CONCLUSION: B cell depletion therapy in patients with pSS results in normalization of the elevated levels of circulating TFH cells. This reduction is associated with improved objective clinical disease activity measures. Our observations illustrate the pivotal role of the crosstalk between B cells and TFH cells in the pathogenesis of pSS.
28648105 Abnormal distribution of AQP4 in minor salivary glands of primary Sjögren's syndrome pati 2017 Jun A decreased saliva production occurs in primary Sjögren's syndrome (pSS), an autoimmune disease characterized by oral and ocular dryness due to dysfunction of the lacrimal and salivary glands (SGs). Since water movement is involved in saliva secretion, the expression, localization, and function of the water channels aquaporins (AQPs) have been extensively studied in SGs. To date, the presence of AQP4 remains controversial and ambiguous in human SGs. We investigated by immunohistochemistry, high-resolution confocal microscopy and quantitative image analysis, Western blot and real-time RT-PCR, the presence of the AQP4 gene, and the distribution of AQP4 protein in healthy controls and pSS SG biopsies. Through the immunohistochemical analysis, we demonstrated that AQP4 presence is confined to the basal region of acini, to the lateral and apical membrane of intercalated and striated ducts in both control and pSS glands. The most striking observation was the discovery of AQP4 localization in myoepithelial cells (MECs) that surround acini lobules and intercalated ducts, and the demonstration of AQP4-downregulated immunoreactivity in pSS MECs. Our studies suggest that the capacity for water flow across the membrane of MECs may be altered in pSS, identifying AQP4 as a promising new therapeutic agent to treat xerostomia.
28507188 Cryoglobulinemia in Sjögren Syndrome: A Disease Subset that Links Higher Systemic Disease 2017 Aug OBJECTIVE: To compare systemic disease activity by validated tools, i.e., the European League Against Rheumatism Sjögren Syndrome Disease Activity Index (ESSDAI) and the Clinical ESSDAI (ClinESSDAI) scores, between primary Sjögren syndrome (pSS) with positive serum cryoglobulins and pSS without serum cryoglobulins. METHODS: There were 825 consecutive patients with pSS who were retrospectively evaluated. RESULTS: The ESSDAI and the ClinESSDAI scores were significantly higher in cryoglobulin-positive patients (p < 0.0001, for both scores). Cryoglobulinemia was significantly associated with these domains: constitutional (p = 0.003), lymphadenopathy (p = 0.007), glandular (p = 0.0002), cutaneous (p < 0.0001), peripheral nervous system (p < 0.0001), hematological (p = 0.004), and biological (p < 0.0001). CONCLUSION: Cryoglobulin-positive patients show the highest systemic activity in pSS.
28487450 Pulmonary MALT Lymphoma in Patients with Sjögren's Syndrome. 2017 Jun To describe clinical features and outcomes of seven patients with pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma in the setting of underlying primary Sjögren's syndrome from a single center, we reviewed medical records of consecutive patients with pulmonary MALT lymphoma evaluated at our facility from January 1, 1999 to December 31, 2015 for clinical features, laboratory, pathologic and radiographic findings, management, and outcomes. Out of 13 patients with pulmonary MALT lymphoma, 7 (54 %) met the criteria for Sjögren's syndrome. The mean age at lymphoma diagnosis was 66 years; male-female ratio was 1:6. One-third of patients were asymptomatic at the time lymphoma was discovered. When symptomatic, patients reported nonspecific pulmonary complaints such as cough and dyspnea. All patients had positive antinuclear antibody and anti-SSA/Ro antibody. Rheumatoid factor was positive in six cases. A monoclonal gammopathy was present in three patients; the remaining four had polyclonal hypergammaglobulinemia. The radiologic, morphologic, and immunohistochemical features of primary Sjögren's syndrome-associated pulmonary MALT lymphomas did not differ significantly from pulmonary MALT lymphoma cases in general. All treatment modalities used resulted in complete and sustained response. One patient died 11 years after initial diagnosis with no lymphoma but of another cause. The remaining six patients are still alive and disease-free to date. The present series confirms the favorable course of pulmonary MALT lymphoma in Sjögren's patients. The overall imaging and pathologic features are in accordance with pulmonary MALT lymphoma not associated with primary Sjögren's syndrome. Further studies should be carried out in order to better understand pulmonary MALT lymphomagenesis, treatment, and outcomes in Sjögren's patients.
29146737 Rheumatic disorders associated with immune checkpoint inhibitors in patients with cancer-c 2018 Mar OBJECTIVES: To evaluate the prevalence and type of rheumatic immune-related adverse events (irAEs) in patients receiving immune checkpoint inhibitors (ICIs), as well as the correlation with tumour response. METHODS: This was a single-centre prospective observational study including all cancer patients receiving ICIs. The occurrence of irAEs and tumour response was assessed on a regular basis. Patients who experienced musculoskeletal symptoms were referred to the department of rheumatology for clinical evaluation and management. RESULTS: From September 2015 to May 2017, 524 patients received ICIs and 35 were referred to the department of rheumatology (6.6%). All but one of the rheumatic irAEs occurred with anti-programmed cell death protein 1(PD-1)/PD-1 ligand 1(PD-L1) antibodies, with a median exposure time of 70 days. There were two distinct clinical presentations: (1) inflammatory arthritis (3.8%) mimicking either rheumatoid arthritis (n=7), polymyalgia rheumatica (n=11) or psoriatic arthritis (n=2) and (2) non-inflammatory musculoskeletal conditions (2.8%; n=15). One patient with rheumatoid arthritis was anti-cyclic citrullinated peptide (anti-CCP) positive. Nineteen patients required glucocorticoids, and methotrexate was started in two patients. Non-inflammatory disorders were managed with non-steroidal anti-inflammatory drugs, analgesics and/or physiotherapy. ICI treatment was pursued in all but one patient. Patients with rheumatic irAEs had a higher tumour response rate compared with patients without irAEs (85.7% vs 35.3%; P<0.0001). CONCLUSION: Since ICIs are used with increasing frequency, knowledge of rheumatic irAEs and their management is of major interest. All patients were responsive either to low-to-moderate doses of prednisone or symptomatic therapies and did not require ICI discontinuation. Furthermore, tumour response was significantly higher in patients who experienced rheumatic irAEs.
28810629 Inhibition of microRNA-34a ameliorates murine collagen-induced arthritis. 2017 Aug Rheumatoid arthritis (RA) is one of the most frequently occurring autoimmne diseases, with symptoms including synovium hyperplasia, immune disorder, cartilage damage and bone resorption. It has previously been demonstrated that microRNA-34a (miR-34a) may participate in cell apoptosis, immune activation and bone metabolism, therefore the present study investigated the effects of miR-34a on RA. Collagen-induced arthritic (CIA) mice were employed as a murine model of experimental arthritis, and it was demonstrated that the level of miR-34a in the spleens, lymph nodes and synovium was increased in the CIA mice compared with normal DBA/1j mice. Administration of miR-34a antagomir, the chemically modified inhibitor, ameliorated CIA and delayed the onset of symptoms. Arthritis scores decreased and joint swelling was alleviated with the miR-34a antagomir treatment and the expression of inflammatory cytokines was decreased. miR-34a antagomir delivery significantly decreased the percentage of T cells present including T helper (Th) 1, Th2, Th17 and regulatory T cells. Furthermore miR-34a antagomir-treated CIA mice demonstrated decreased inflammatory-induced bone loss. Overall, it was observed that inhibition of miR-34a ameliorated murine arthritis, downregulated T cell percentage and cytokine expression, and suppressed bone loss. The experimental results suggest that inhibition of miR-34a may offer a novel alternative for the treatment of RA.
28589069 Looks Can Be Deceiving: A Case Report on Multicentric Reticulohistiocytosis Successfully T 2017 May 3 Multicentric reticulohistiocytosis (MRH) is an idiopathic multisystemic inflammatory disease characterized by symmetric erosive polyarthritis and typical papulonodular skin lesions. MRH can be associated with autoimmune diseases, malignancy, mycobacterial infections, and hyperlipidemia, and it is important to consider appropriate screening in this population. There is no specific diagnostic laboratory test for MRH. The gold standard for diagnosis is skin or synovial biopsy, which shows characteristic multinucleated non-Langerhans giant cells and ground glass eosinophilic cytoplasm. Although the disease spontaneously remits in approximately 10 years, MRH can rapidly progress to arthritis mutilans in the majority of cases. The diagnosis and treatment are challenging due to its low prevalence and lack of robust guidelines from major rheumatological societies. Corticosteroids and methotrexate are generally first-line treatment options. However, more recently, biologic agents have been increasingly used in refractory cases with some success. Early diagnosis is crucial in preventing disease progression. We report a case of MRH in a patient whose clinical presentation mimicked rheumatoid arthritis and was subsequently treated successfully with rituximab.
29081987 Synovial fibroblasts in 2017. 2017 Stromal cells like synovial fibroblasts gained great interest over the years, since it has become clear that they strongly influence their environment and neighbouring cells. The current review describes the role of synovial fibroblasts as cells of the innate immune system and expands on their involvement in inflammation and cartilage destruction in rheumatoid arthritis (RA). Furthermore, epigenetic changes in RA synovial fibroblasts and studies that focused on the identification of different subsets of synovial fibroblasts are discussed.
29326938 Key Triggers of Osteoclast-Related Diseases and Available Strategies for Targeted Therapie 2017 Osteoclasts, the only cells with bone resorption functions in vivo, maintain the balance of bone metabolism by cooperating with osteoblasts, which are responsible for bone formation. Excessive activity of osteoclasts causes many diseases such as osteoporosis, periprosthetic osteolysis, bone tumors, and Paget's disease. In contrast, osteopetrosis results from osteoclast deficiency. Available strategies for combating over-activated osteoclasts and the subsequently induced diseases can be categorized into three approaches: facilitating osteoclast apoptosis, inhibiting osteoclastogenesis, and impairing bone resorption. Bisphosphonates are representative molecules that function by triggering osteoclast apoptosis. New drugs, such as tumor necrosis factor and receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors (e.g., denosumab) have been developed for targeting the receptor activator of nuclear factor kappa-B /RANKL/osteoprotegerin system or CSF-1/CSF-1R axis, which play critical roles in osteoclast formation. Furthermore, vacuolar (H(+))-ATPase inhibitors, cathepsin K inhibitors, and glucagon-like peptide 2 impair different stages of the bone resorption process. Recently, significant achievements have been made in this field. The aim of this review is to provide an updated summary of the current progress in research involving osteoclast-related diseases and of the development of targeted inhibitors of osteoclast formation.
28303136 Expansions of Cytotoxic CD4(+)CD28(-) T Cells Drive Excess Cardiovascular Mortality in Rhe 2017 A large proportion of cardiovascular (CV) pathology results from immune-mediated damage, including systemic inflammation and cellular proliferation, which cause a narrowing of the blood vessels. Expansions of cytotoxic CD4(+) T cells characterized by loss of CD28 ("CD4(+)CD28(-) T cells" or "CD4(+)CD28(null) cells") are closely associated with cardiovascular disease (CVD), in particular coronary artery damage. Direct involvement of these cells in damaging the vasculature has been demonstrated repeatedly. Moreover, CD4(+)CD28(-) T cells are significantly increased in rheumatoid arthritis (RA) and other autoimmune conditions. It is striking that expansions of this subset beyond 1-2% occur exclusively in CMV-infected people. CMV infection itself is known to increase the severity of autoimmune diseases, in particular RA and has also been linked to increased vascular pathology. A review of the recent literature on immunological changes in CVD, RA, and CMV infection provides strong evidence that expansions of cytotoxic CD4(+)CD28(-) T cells in RA and other chronic inflammatory conditions are limited to CMV-infected patients and driven by CMV infection. They are likely to be responsible for the excess CV mortality observed in these situations. The CD4(+)CD28(-) phenotype convincingly links CMV infection to CV mortality based on a direct cellular-pathological mechanism rather than epidemiological association.
27895095 Calprotectin in rheumatic diseases. 2017 Apr Calprotectin is a heterodimer formed by two proteins, S100A8 and S100A9, which are mainly produced by activated monocytes and neutrophils in the circulation and in inflamed tissues. The implication of calprotectin in the inflammatory process has already been demonstrated, but its role in the pathogenesis, diagnosis, and monitoring of rheumatic diseases has gained great attention in recent years. Calprotectin, being stable at room temperature, is a candidate biomarker for the follow-up of disease activity in many autoimmune disorders, where it can predict response to treatment or disease relapse. There is evidence that a number of immunomodulators, including TNF-α inhibitors, may reduce calprotectin expression. S100A8 and S100A9 have a potential role as a target of treatment in murine models of autoimmune disorders, since the direct or indirect blockade of these proteins results in amelioration of the disease process. In this review, we will go over the biologic functions of calprotectin which might be involved in the etiology of rheumatic disorders. We will also report evidence of its potential use as a disease biomarker. Impact statement Calprotectin is an acute-phase protein produced by monocytes and neutrophils in the circulation and inflamed tissues. Calprotectin seems to be more sensitive than CRP, being able to detect minimal residual inflammation and is a candidate biomarker in inflammatory diseases. High serum levels are associated with some severe manifestations of rheumatic diseases, such as glomerulonephritis and lung fibrosis. Calprotectin levels in other fluids, such as saliva and synovial fluid, might be helpful in the diagnosis of rheumatic diseases. Of interest is also the potential role of calprotectin as a target of treatment.
27165981 Ultrasound imaging of the distal radioulnar joint: a new method to assess ulnar radial tra 2017 May A cross-sectional reliability study was conducted with 23 normal participants to establish normal values, and the repeatability and validity of distal radioulnar joint translation measurements using ultrasound imaging. Static transverse images of maximal supination, neutral and maximal pronation were examined to assess translation, using a method consistent with the rheumatoid arthritis subluxation ratio. Translation while gripping a 1 kg weight in supinated and pronated positions was then compared with non-gripping translation. There was significantly more ulnar radial translation found with pronation than supination, when compared with neutral. Gripping in pronation did not produce statistically significant changes in translation, whereas the changes produced by gripping in supination were significant. Internal consistency was deemed very high and the rheumatoid arthritis subluxation ratio values measured using ultrasound imaging were consistent with previously documented values measured by computerized tomography. This study demonstrated that translational movement of the distal radioulnar joint can be reliably detected in healthy participants using ultrasound imaging. This may reduce dependency on other imaging modalities to diagnose distal radioulnar joint instability. LEVEL OF EVIDENCE: 2.
28777803 GM-CSF in murine psoriasiform dermatitis: Redundant and pathogenic roles uncovered by anti 2017 Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic, Th17-derived cytokine thought to critically contribute to the pathogenesis of diverse autoimmune diseases, including rheumatoid arthritis and psoriasis. Treatment with monoclonal antibodies that block GM-CSF activity is associated with favorable therapeutic effects in patients with rheumatoid arthritis. We evaluated the role of GM-CSF as a potential target for therapeutic interference in psoriasis using a combined pharmacologic and genetic approach and the mouse model of imiquimod-induced psoriasiform dermatitis (IMQPD). Neutralization of murine GM-CSF by an anti-GM-CSF antibody ameliorated IMQPD. In contrast, genetic deficiency in GM-CSF did not alter the course of IMQPD, suggesting the existence of mechanisms compensating for chronic, but not acute, absence of GM-CSF. Further investigation uncovered an alternative pathogenic pathway for IMQPD in the absence of GM-CSF characterized by an expanded plasmacytoid dendritic cell population and release of IFNα and IL-22. This pathway was not activated in wild-type mice during short-term anti-GM-CSF treatment. Our investigations support the potential value of GM-CSF as a therapeutic target in psoriatic disease. The discovery of an alternative pathogenic pathway for psoriasiform dermatitis in the permanent absence of GM-CSF, however, suggests the need for monitoring during therapeutic use of long-term GM-CSF blockade.
28717403 The potential role of adult stem cells in the management of the rheumatic diseases. 2017 Jul Adult stem cells are considered as appealing therapeutic candidates for inflammatory and degenerative musculoskeletal diseases. A large body of preclinical research has contributed to describing their immune-modulating properties and regenerative potential. Additionally, increasing evidence suggests that stem cell differentiation and function are disrupted in the pathogenesis of rheumatic diseases. Clinical studies have been limited, for the most part, to the application of adult stem cell-based treatments on small numbers of patients or as a 'salvage' therapy in life-threatening disease cases. Nevertheless, these preliminary studies indicate that adult stem cells are promising tools for the long-term treatment of rheumatic diseases. This review highlights recent knowledge acquired in the fields of hematopoietic and mesenchymal stem cell therapy for the management of systemic sclerosis (SSc), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and osteoarthritis (OA) and the potential mechanisms mediating their function.
29445556 Immunotherapy for Metastatic Melanoma with Right Atrial Involvement in a Patient with Rheu 2017 Prognosis for metastatic melanoma has improved significantly with the use of immune checkpoint inhibitors. Given improvements in survival, aggressive surgical treatment may be considered in patients with life-threatening complications from their disease that would not otherwise be considered in advanced disease. Patients with preexisting autoimmune diseases or prior immune-related adverse events from therapy are largely excluded from clinical trials. Concerns exist that immunotherapy in these patients could worsen autoimmune disease or increase the risk of developing additional immune-related adverse events on therapy. We present a case of a patient with rheumatoid arthritis that presented with obstructive heart failure secondary to melanoma that had metastasized to the right atrium. After aggressive surgical resection to stabilize him from his life-threatening heart failure, he was treated with ipilimumab, which was stopped due to an immune-related adverse event. He was then started on pembrolizumab and had a durable response to therapy. Aggressive surgical treatment should be considered in patients with a cancer that may respond to immunotherapy. Furthermore, some patients with preexisting autoimmune disease may be safely treated with checkpoint inhibition therapy, and patients with a severe immune toxicity from one class may successfully be treated with an alternate class.
27480610 A novel approach to cricoarytenoid joint injections: An anatomic study. 2017 Jan OBJECTIVES: To demonstrate a novel approach to cricoarytenoid joint (CAJ) injections. STUDY DESIGN: Anatomic feasibility study. METHODS: Five human cadaveric larynges providing 10 CAJ s were used to obtain trajectory measurements of a 27-gauge 1½-inch needle placed between the CAJ capsule and the contralateral cricothyroid membrane. Ten additional larynges providing 20 CAJ s were then used to assess the efficacy of applying the previously obtained measurements to guide 0.2-cc methylene blue injections of the CAJ using a 27-gauge 1½-inch needle. Successful injection was confirmed by direct visualization of methylene blue within the CAJ capsule. RESULTS: The tip of the needle made a 70 ± 1.87 degree (confidence interval [CI] 95%) angle relative to the plane parallel to the anterior lamella of the cricoid cartilage; the needle was within the cricothyroid membrane 5 ± 0.77 mm (CI 95%) lateral to the midsagittal plane; the needle was 4 ± 0.80 mm (CI 95%) anteroinferior from the vocal process of the arytenoid cartilage as measured within the airway; and the distance from the point of airway entry and the CAJ capsule was 17 ± 2.42 mm (CI 95%). Twenty CAJ injections were attempted using the guidelines established here with an 85% success rate. CONCLUSION: The current approach to CAJ injection utilizes microlaryngoscopy in an operative setting. This study is the first to describe the accessibility of the CAJ through percutaneous injection using reliable landmarks, potentially allowing access to the joint in an office-based setting. LEVEL OF EVIDENCE: NA Laryngoscope, 127:199-203, 2017.
29065914 Seroprevalence of Toxoplasma gondii infection in arthritis patients in eastern China. 2017 Oct 25 BACKGROUND: There is accumulating evidence for an increased susceptibility to infection in patients with arthritis. We sought to understand the epidemiology of Toxoplasma gondii infection in arthritis patients in eastern China, given the paucity of data on the magnitude of T. gondii infection in these patients. METHODS: Seroprevalence of T. gondii infection was assessed by enzyme-linked immunosorbent assay using a crude antigen of the parasite in 820 arthritic patients, and an equal number of healthy controls, from Qingdao and Weihai cities, eastern China. Sociodemographic, clinical and lifestyle information on the study participants were also obtained. RESULTS: The prevalence of anti-T. gondii IgG was significantly higher in arthritic patients (18.8%) compared with 12% in healthy controls (P < 0.001). Twelve patients with arthritis had anti-T. gondii IgM antibodies - comparable with 10 control patients (1.5% vs 1.2%). Demographic factors did not significantly influence these seroprevalence frequencies. The highest T. gondii infection seropositivity rate was detected in patients with rheumatoid arthritis (24.8%), followed by reactive arthritis (23.8%), osteoarthritis (19%), infectious arthritis (18.4%) and gouty arthritis (14.8%). Seroprevalence rates of rheumatoid arthritis and reactive arthritis were significantly higher when compared with controls (P < 0.001 and P = 0.002, respectively). A significant association was detected between T. gondii infection and cats being present in the home in arthritic patients (odds ratio [OR], 1.68; 95% confidence interval [CI]: 1.24 - 2.28; P = 0.001). CONCLUSIONS: These findings are consistent with and extend previous results, providing further evidence to support a link between contact with cats and an increased risk of T. gondii infection. Our study is also the first to confirm an association between T. gondii infection and arthritis patients in China. Implications for better prevention and control of T. gondii infection in arthritis patients are discussed. TRIAL REGISTRATION: This is an epidemiological survey, therefore trial registration was not required.
28740368 Impact of adherence to biological agents on health care resource utilization for patients 2017 OBJECTIVE: Poor adherence to therapy increases the patient and societal burden and complexity of chronic diseases such as rheumatoid arthritis (RA). In the past 15 years, biologic disease-modifying anti-rheumatic drugs (DMARDs) have revolutionized the treatment of RA. However, little data are available on the impact of adherence to biologics on health care resources. The objective of the study was to determine the long-term health care resource utilization patterns of RA patients who were adherent to biologic DMARD therapy compared to RA patients who were non-adherent to biologic DMARD therapy in an Ontario population and to determine factors influencing adherence. METHODS: Patients were identified from the Ontario RA Database that contains all RA patients in Ontario, Canada, identified since 1991. The study population included RA patients, aged 65+ years, with a prescription for a biologic DMARD between 2003 and 2013. Exclusion criteria included diagnosis of inflammatory bowel disease, psoriatic arthritis or psoriasis in the 5 years prior to the index date and discontinuation of biologic DMARD, defined as no subsequent prescription during the 12 months after the index date. Adherence was defined as a medication possession ratio of ≥0.8 measured as the proportion of days for which a patient had biologic treatment(s) over a defined follow-up period. Adherent patients were matched to non-adherent patients by propensity score matching. RESULTS: A total of 4,666 RA patients were identified, of whom 2,749 were deemed adherent and 1,917 non-adherent. The age (standard deviation) was 69.9 (5.46) years and 75% were female. Relative rates for resource use (physician visits, emergency visits, hospitalization, home care and rehabilitation) for the matched cohort were significantly lower (P⩽0.0001) in adherent patients. Non-adherent patients' use of oral prednisone (67%) was significantly higher (P⩽0.001) than that of the adherent cohort (56%). CONCLUSION: RA patients adherent to biologic therapy have lower health care resource use and lower steroid use compared to non-adherent patients.
28063059 Experimental Arthritis Mouse Models Driven by Adaptive and/or Innate Inflammation. 2017 Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease mainly affecting synovial joints. The clinical presentation of RA shows the heterogeneity of this disease with its underlying complex interactions between the innate and adaptive immune system and flare-ups of disease. Different disease models such as collagen induced arthritis, antigen induced arthritis, and Streptococcal cell wall induced arthritis can be exploited to investigate different aspects of the pathogenesis of arthritis. The disease can be monitored macroscopically over time via scoring systems. For histological examination, paraffin embedded knee sections can be used for hematoxylin and eosin staining to visualize cellular infiltration as well as for tartrate-resistant acid phosphatase (TRAP) staining to identify osteoclast-like cells. Cellular infiltration of the synovium by different myeloid cells such as tissue resident macrophages, dendritic cells and neutrophils can be monitored using flow cytometry. Here, we describe the methods for inducing the different mouse models for arthritis, including scoring systems per model, histological and flow cytometric analysis.
28093613 Recent trends in the distribution of causative diseases of fever of unknown origin. 2017 Mar Fever of unknown origin is a challenging diagnostic problem and the aim of this research was to analyze trends in the distribution of its causative diseases. This retrospective study makes a comparison between two different clinical series of patients from two different periods: 227 from period 1 (1998-2002) and 602 from period 2 (2008-2012). There were fewer infections (31.72% vs.16.45%) and more miscellaneous causes (5.29% vs. 13.12%) in the period 2 series, whereas no significant differences in autoimmune diseases, malignancies and undiagnosed cases were found. Adult onset Still's disease and lymphoma occupied the largest proportion in autoimmune diseases (75.00%) and malignancies (89.81%), respectively. Interestingly, the autoimmune diseases group, instead of infections, was found to be the leading category of the causative diseases in fever of unknown origin, which is contrary to previous reports. Further, adult onset Still's disease and lymphoma were suggested to be valued more highly in view of the large and rising proportions found in this study. These trends could support the diagnosis and treatment of fever of unknown origin better in the future.