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ID PMID Title PublicationDate abstract
31629652 Outcomes of semiconstrained total elbow arthroplasty performed for arthritis in patients u 2020 Apr BACKGROUND: Total elbow arthroplasty (TEA) is a treatment option for end-stage arthritis. Even though results are satisfactory for the elderly population, TEA surgery is subject to controversy in younger patients. The purpose of this study was to evaluate clinical and radiographic outcomes of semiconstrained TEA performed for arthritis in patients younger than 55 years. MATERIALS AND METHODS: Between 1998 and 2008, 19 TEAs were implanted in 17 patients younger than 55 years (mean age, 46 years; range, 29-54 years). We assessed the indication for further surgery; range of motion; mean Mayo Elbow Performance Score; QuickDASH (short version of the Disabilities of the Arm, Shoulder and Hand questionnaire) score; radiolucent lines; and outcome measures that included implant survival, complications, and revisions. RESULTS: The average follow-up period was 10 years (range, 2-16 years). Average range of motion significantly improved, from 120° (range, 90°-140°) to 140° (range, 130°-155°) for flexion and from 40° (range, 0°-60°) to 25° (range, 0°-90°) for extension. The average Mayo Elbow Performance Score was 85 (range, 55-100). During the study period, 11 elbows (58%) experienced complications and 8 (42%) underwent revision. Aseptic loosening (3 ulnar and 2 bipolar) was the main indication for revision. The survivorship rate without revision was 94% at 5 years and 75% at 10 years. CONCLUSIONS: TEA gave satisfactory results in a younger patient population. However, a high rate of complications and revisions was observed with follow-up. Thus, TEA should be considered with caution in young patients, and other therapeutic options must be discussed.
31629046 New Lignans from roots of Kadsura coccinea. 2019 Nov Four new dibenzocyclooctadiene lignans, named heilaohusus A-D (1-4), one new arylnaphthalene lignan named heilaohusu E (5), and seven known analogues (6-12) were isolated from the roots of Kadsura coccinea. Their structures and configurations were elucidated by a combination of HR-ESI-MS, (1)H NMR, (13)C NMR, HSQC, HMBC, NOESY and CD spectra. Among the known compounds, compounds 6 and 8-12 were isolated from this plant for the first time. All of compounds were evaluated for their cytotoxicity activities, compounds 3, 6 and 7 showed weak cytotoxicity against four human cancer cell lines (HepG-2, HCT-116, BGC-823 and Hela) with IC(50) values range from 13.04 to 21.93 μM. Compounds 1 and 7 demonstrated potential anti-RA (rheumatoid arthritis) activity against RA-FLS cell line with IC(50) values of 14.57 and 11.70 μM, respectively.
30834567 UHPLC-MS/MS analysis of sphingosine 1-phosphate in joint cavity dialysate and hemodialysis 2019 Jul Geniposide (GE) is an iridoid glycoside compound with anti-inflammatory effect. The potential of sphingosine 1-phosphate (S1P) as a plasma marker in human diseases was suggested recently in the literature, which demonstrated that, in patients with inflammatory diseases, plasma S1P was elevated. It follows that the obstructive coronary artery disease can be predicted with serum S1P. Therefore, S1P can also be potentially used as a pharmacodynamic marker to study adjuvant arthritis (AA) rats. In the current study, a UHPLC-MS/MS method combined with the microdialysis sampling technique (using FTY720 phosphate as an internal standard) was adopted and validated to measure S1P levels in the hemodialysis fluid and joint cavity dialysates of AA rats after oral administration of GE. A S1P concentration-time curve in the dialysate was established in this study. It was demonstrated that GE exerted an anti-inflammatory effect by reducing AA-induced elevated S1P levels. It is showed that changes in S1P concentrations over time can be used to monitor the pharmacodynamic effects of GE in treating AA rats in pharmacodynamic studies.
31720751 Resolution of inflammation in arthritis. 2019 Nov Rheumatoid arthritis is among the most frequent and severe chronic inflammatory diseases. The disease is characterized by ongoing synovial inflammation, which leads to the destruction of cartilage and bone. In RA, the mechanisms of resolution of inflammation, which are normally intact in the joints, are either suppressed or overruled. Little efforts have been undertaken to understand the mechanisms of resolution of arthritis until recently, when several molecular mechanisms have been identified that determine the chronicity and resolution of inflammation in the joints, respectively. This review describes the key concepts of resolution of arthritis mentioning the key mechanisms involved, such as regulatory macrophages, pro-resolving lipid, fatty acid and cytokine mediators, aggregated neutrophil extracellular trap formation, antibody glycosylation changes, and stromal cell alterations that are involved in determining the decision between chronicity and resolution of arthritis. Each of these mechanisms represents a potential therapeutic approach that allows skewing the balance of the inflammatory processes towards resolution.
31062502 Vasoactive intestinal peptide-induced tolerogenic dendritic cells attenuated arthritis in 2019 Jul AIM: Cumulative evidence has revealed that tolerogenic dendritic cells (tolDC) could relieve inflammation reactions in various autoimmune diseases. This study investigated the potential therapeutic application of vasoactive intestinal peptide (VIP)-induced tolDC (VIP-DC) on arthritis using collagen-induced arthritis (CIA) mice. METHODS: Bone marrow cells were differentiated into dendritic cells (DC) using granulocyte macrophage colony-stimulating factor and interleukin (IL)-4. tolDC were induced by either VIP or Bay 11-7082 in vitro. Immunophenotypes and cytokine production of VIP-DC and Bay-DC were detected by fluorescence-activated cell sorting and enzyme-linked immunosorbent assay, respectively. Bay-DC, VIP-DC and untreated DC were ip administrated to CIA mice on day 40 when arthritis was onset. The treatment effects on arthritic and pathological changes, including synovial hyperplasia, pannus formation, inflammation and bone erosion, were assessed. RESULTS: VIP-DC (40 ng/mL) and Bay-DC (0.5 µg/mL) had a lower level of major histocompatibility complex II, CD40 and CD86 expression, reduced γ-interferon and increased IL-4 production (P < 0.05 or 0.01), compared with untreated DC. The administration of VIP-DC and Bay-DC decreased the arthritis score clinically at the end of the therapy. Pathological assessments showed that bone erosion and inflammation were alleviated in the VIP-DC group compared with those in the untreated DC group (P < 0.05 and P < 0.01, respectively). CONCLUSION: VIP-DC showed reduced immunogenicity and enhanced anti-inflammatory cytokine production. Both VIP-DC and Bay-DC could ameliorate arthritis in CIA mice clinically. VIP-DC were not inferior to Bay 11-7082-induced tolDC but may exert a better preventive effect on bone destruction.
31286787 Emerging drugs for primary Sjögren's syndrome. 2019 Jun Introduction: Primary Sjögren's syndrome (pSS) is an autoimmune systemic disease characterized by a complex and not yet completely elucidated etiopathogenesis, where autoimmune manifestations coexist with different degree of lymphoproliferation, resulting in multiple possible scenarios extremely heterogeneous from patient to patient. Although considerable progress has been made in the identifications of potential novel therapeutic targets in recent years, the biological complexity of pSS, combined to such heterogeneous clinical manifestations, makes the treatment of pSS, even today, a great challenge. Areas covered: A therapy specifically approved for pSS is still lacking. In recent years, several novel promising agents are being tested in pSS. Based on a deep revision of drugs evaluated for pSS therapy, it is striking that several clinical trials, some of them testing very promising agents, failed. Expert opinion: a renewal of clinical trial design, including the definition of novel inclusion criteria and outcome measures, together with the development of a stratification model of pSS patients and the advance in the definition of pathogenetic mechanisms underlying peculiar pSS subsets, represent preliminary and crucial steps to overcome the current therapeutic impasse in pSS.
30422723 Comparison of patients with and without pre-existing lymphoma at diagnosis of primary Sjö 2019 May OBJECTIVE: In the 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren's syndrome (pSS), pre-existing lymphoma is not an exclusion criterion for pSS diagnosis, as in earlier criteria. We aimed to explore whether there are differences between pSS patients with and without pre-existing lymphoma at pSS diagnosis. METHOD: Patients with ICD-7-10 codes for Sjögren's syndrome (SS) and a diagnosis of malignant lymphoma before or after SS diagnosis were identified by linking the Swedish Patient Register 1964-2007 with the Cancer Register 1990-2007 (n = 224). Clinical data were collected from medical records. Lymphoma diagnoses were evaluated by tissue review. Characteristics of pSS patients with and without pre-existing lymphoma were compared. RESULTS: We identified 107 patients with pSS as the reason for an SS diagnosis code and a verified lymphoma. Of these, 18 (17%) had a pre-existing lymphoma at pSS diagnosis, defined as lymphoma diagnosed before or within 6 months of pSS diagnosis. Male gender (39% vs 10%, p = 0.006), enlarged lymph nodes during the pSS disease (61% vs 27%, p = 0.01), mucosa-associated lymphoid tissue (MALT) lymphoma (50% vs 22%, p = 0.02), and salivary gland lymphoma (61% vs 26%, p = 0.006) were more common in patients with a pre-existing lymphoma at pSS diagnosis. Other pSS characteristics were similar. CONCLUSION: In a substantial proportion of patients, particularly in men, pSS remains undiagnosed until after lymphoma diagnosis. The study highlights the importance of pSS investigation in patients with lymphoma, especially MALT lymphoma, in the salivary glands.
31763772 Prevalence, correlates, and impact of sleep disturbance in Chinese patients with primary S 2020 Mar AIM: Sleep disturbances are common in primary Sjögren's syndrome (pSS) patients and may lead to disease aggravation and decreased health-related quality of life (HRQoL). There are currently no known reported studies related to the prevalence, correlates, and impact of sleep disturbance in pSS patients from China. Therefore, this study aims to assess the sleep quality in Chinese pSS patients and evaluate its relationship with the disease activity, quality of life and mood disorders. METHODS: A self-report survey was administered to 221 pSS patients and 198 healthy individuals using the Pittsburgh Sleep Quality Index (PSQI) for sleep quality. Disease activity and damage were evaluated with the European League Against Rheumatism Sjögren's syndrome disease activity index (ESSDAI). Independent samples t tests, Chi-square analysis, logistic regression were used to analyze these data. RESULTS: Our results found that the prevalence of poor sleep (PSQI ≥ 6) was 57.5% and the mean global score of PSQI was 6.57 (SD 3.19) in patients, which were significantly higher than the controls (32.3% and 4.93 [SD 2.86], respectively). When trying to fall asleep, patients with pSS had some sleep disturbances, reduced sleep efficiency, increased number of awakenings than controls. There were significant correlations among dryness, ocular surface disease, HRQoL, pain, disease activity, anxiety/depression and sleep quality in pSS patients. Meanwhile, logistic regression models identified depression and Short Form-36 mental composite score as predictors of poor sleep quality. CONCLUSIONS: Sleep disturbances are commonly reported in pSS patients and sleep quality is lower in pSS patients than in healthy controls. The data suggested the need for holistic assessment and management of pSS patients.
31376264 Distinct clinical characteristics of anti-Ro/SSA-negative primary Sjögren's syndrome: dat 2019 May OBJECTIVES: To investigate clinical characteristics of patients with primary Sjögren's syndrome (SS) who were negative for anti-Ro/SSA antibody but positive for minor salivary gland biopsy (MSGB) compared to patients who presented positivity for anti-Ro/SSA antibody. METHODS: The data of 355 patients from the Korean Initiative of primary Sjögren's Syndrome (KISS), a nationwide prospective cohort for primary SS in Korea, were analysed. All patients fulfilled the 2016 American College of Rheumatology/European League Against Rheumatism (EULAR) classification criteria. Of these patients, 326 were positive for anti-Ro/SSA antibody and 29 were antibody-negative, although they had positive findings in MSGB. Various clinical features including all kinds of tests for evaluating secretory function, disease-related clinical indices and serological values available in the cohort were compared between the two groups. RESULTS: The anti-Ro/SSA-negative group showed less rheumatoid factor positivity (p<0.001), leucopenia (p=0.003), hyper-gammaglobulinaemia (p<0.001), lower serum β2-microglobulin level (p=0.034), more anti-centromere antibody positivity (p<0.001), higher score in dryness domain of EULAR SS patient-reported index (p=0.048) and more positivity for peripheral nervous system domain in EULAR SS disease activity index and loss of teeth in SS disease damage index (p=0.021 and 0.041, respectively) than patients who were positive for anti-Ro/ SSA antibody. CONCLUSIONS: Primary SS patients who are negative for anti-Ro/SSA antibody have different clinical characteristics compared to patients who are positive for such antibody in Korea. Therefore, clinicians should consider MSGB in patients with suspicious symptoms who are anti-Ro/SSA-negative.
30682880 Distorted Taste and Impaired Oral Health in Patients with Sicca Complaints. 2019 Jan 24 Senses of smell and taste, saliva flow, and dental status are considered as important factors for the maintenance of a good nutritional status. Salivary secretory rates, chemosensory function, burning mouth sensation, halitosis and dental status were investigated in 58 primary Sjögren's syndrome (pSS) patients, 22 non-Sjögren's syndrome sicca (non-SS) patients, and 57 age-matched healthy controls. A significantly greater proportion of pSS and non-SS patients had ageusia, dysgeusia, burning mouth sensation, and halitosis compared to controls. Patients with pSS had significantly lower olfactory and gustatory scores, and significantly higher caries experience compared to controls. Patients with pSS and non-SS patients had significantly lower unstimulated and stimulated whole saliva secretory rates compared to controls. The findings indicated that several different aspects of oral health were compromised in both pSS and non-SS patients, and this may affect their food intake and, hence, their nutritional status. Although non-SS patients do not fulfill Sjögren's syndrome classification criteria, they have similar or, in some cases, even worse oral complaints than the pSS patients. Further studies are needed to investigate food preferences, dietary intake, and nutritional status in these two patient groups in relation to their health condition.
30273514 Effect of Rapamycin Microspheres in Sjögren Syndrome Dry Eye: Preparation and Outcomes. 2019 Purpose: To prepare a drug delivery system of rapamycin poly-3-hydroxybutyrate-co-3-hydroxyvalerate microspheres (RPM) and analyze its effect on the eyes of a Sjögren's syndrome mouse model.Methods: RPM was generated using a solvent evaporation method, and observed under light and electron microscopy. No obesity diabetes (NOD) mice with Sjögren's syndrome were randomized into normal saline, empty microspheres, and RPM groups, with healthy Kunming mice as the controls. Dry eye signs were assessed using a slit lamp. Tear secretion, corneal fluorescein, keratoconjunctival rose bengal, and conjunctival impression cytology were recorded.Results: RPM was smooth and spherical, about 20-50 μm in diameter, without agglomeration or adhesion. Mice receiving RPM secreted more tears. And they had a normal corneal histology, exhibiting reduced corneal fluorescein, rose bengal staining, and conjunctival impression cytology.Conclusion: RPM improved the signs of dry eyes, improved tear secretion, decreased corneal endothelial cell injury, and improved histological damage of the cornea in NOD mice.
31673417 Anti-RNP positivity in primary Sjögren's syndrome is associated with a more active diseas 2019 OBJECTIVES: To describe and compare the clinical and biological characteristics of subjects with primary Sjögren's syndrome (pSS) with and without anti-RNP antibodies. METHODS: Patients fulfilling the American College of Rheumatology (ACR)/EULAR 2016 criteria for pSS and having anti-RNP antibodies, without other connective tissue disease diagnosed and no anti-dsDNA antibodies were retrieved from the database from our French National Reference Center. These patients were compared with all other patients with pSS with negative anti-Sm, anti-RNP and anti-dsDNA antibodies. RESULTS: Overall, 21 patients with pSS positive for anti-RNP antibodies and 446 negative for anti-RNP antibodies were retrieved. Anti-RNP-positive patients had a lower median age at onset of pSS symptoms (41.0 vs 50.0 years, p=0.01), a higher median EULAR Sjögren's syndrome disease activity index at inclusion (8.0 vs 3.0, p<0.01), more frequently constitutional symptoms (14.3% vs 0.01%, p<0.01), myositis (19.0% vs 2.3%, p<0.01) and pulmonary (19.0% vs 5.7%, p=0.04) involvement. Moreover, anti-RNP-positive patients had higher median gammaglobulin levels (22.5 vs 13 g/L, p<0.01), more frequently anti-SSA antibodies (90.5% vs 67.1%, p=0.03), but less frequent lymphocytic sialadenitis with a focus score ≥1 (66.7% vs 85.5%, p=0.03). If the analysis is restricted to anti-SSA-positive patients, anti-RNP positivity is associated with the same clinicobiologic features except the pulmonary involvement. CONCLUSION: Patients with pSS with anti-RNP antibodies displayed a more active systemic disease, with more frequent muscular and pulmonary involvement, and increased gammaglobulin level, compared with anti-RNP-negative patients.
31361930 Urticarial rash, fever, and arthritis: A case of refractory Adult-onset Still's disease wi 2019 Sep Adult-onset Still's disease (AOSD) is a rare, systemic inflammatory disorder of not completely understood etiology. Aberrant activation of the innate immune system and overproduction of several pro-inflammatory mediators are considered a critical component in disease pathogenesis. AOSD still poses a challenge due to the broad range of differential diagnoses and no specific biomarkers. Four cardinal symptoms are quotidian spiking fever, joint involvement, evanescent salmon pink-rash rash, and leukocytosis with neutrophilia. We present a case of a 61-year-old female with a recurrent urticarial rash accompanied by attacks of high fever, tender joints, sore throat, enlarged liver, elevated inflammatory reactants, and hyperferritinemia. After an extensive workup, the patient fulfilled the criteria of AOSD. She was refractory to the glucocorticosteroids and disease-modifying anti-rheumatic drugs (DMARDs). Finally, after several unsuccessful attempts to achieve disease control with traditional DMAR's administration of Tocilizumab (TCZ), a humanized anti-IL-6 receptor antagonist resulted in substantial disease improvement. Since skin manifestations are a common feature of AOSD, it should be among differential diagnoses in patients with skin lesions and constitutional symptoms. Biologic agents represent a significant therapeutic advance in patients with AOSD refractory to conventional therapy.
31263993 Prescribing motivations and patients' characteristics related to the use of biologic drugs 2020 Jan A growing body of evidence suggests the usability of biologic disease-modifying anti-rheumatic drugs (bDMARDs) in treating adult-onset Still's disease (AOSD). In a multicentre "real-life" cohort, the physicians' prescribing motivations and patients' predictive characteristics of being treated with bDMARDs were assessed. Patients with AOSD, who were included in GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) cohort and treated with bDMARDs, were retrospectively assessed. Relevant data were collected by a review of clinical charts. Forty-four patients treated with bDMARDs were analysed, with slight male preponderance (52.3%) and a mean age of 39.3 ± 15.2 years. All patients were treated with corticosteroids (CCSs) (38.6% with low dosage) and 93.2% were treated with synthetic DMARDs (sDMARDs). Regarding the effectiveness of the first-line bDMARD, 65.6% of patients experienced a complete remission, defined as complete disappearance of both systemic and joint symptoms and normalisation of laboratory evidence of disease. The physicians' prescribing motivations for bDMARDs were inadequate response to CCSs and/or sDMARDs, CCS-sparing effect and occurrence of macrophage activation syndrome (MAS). Analysing patients' characteristics, chronic disease course (OR 3.09; 95%CI 1.22-7.80, p = 0.017), defined as disease with persistent symptoms, was predictive of being treated with bDMARDs, whereas age (OR 0.97, 95%CI 0.93-0.99, p = 0.048) was negatively associated, suggesting younger age as a further predictive factor. Patients with AOSD were treated with bDMARDs for inadequate response to CCSs and/or sDMARDs, CCS-sparing effect and MAS occurrence. Younger age and chronic disease course were patients' predictive characteristics of being treated with bDMARDs.
30920100 Oral epithelial membrane-associated mucins and transcriptional changes with Sjögren's syn 2019 Jul OBJECTIVES: To determine expression and localization of membrane-associated mucins within human keratinized and non-keratinized oral epithelia, and to explore transcriptional changes associated with primary Sjögren's syndrome. SUBJECTS AND METHODS: Mucin transcripts and glycoproteins were determined by RT-PCR and immunohistochemistry, respectively, in oral keratinized (hard palate) and non-keratinized (buccal) epithelia obtained from three cadavers. Mucin transcripts assessed by quantitative PCR were compared between cells harvested by brushing buccal and palatal epithelia of 25 female primary Sjögren's syndrome patients vs 25 healthy age-matched female control subjects. RESULTS: In hard palate, MUC4 is absent and MUC1 localized to deeper cell layers. Both mucins are within the apical layers of buccal epithelium. MUC15 is localized throughout all palatal cell layers and in all but the basal layer of buccal epithelia. MUC16, MUC20, and MUC21 glycoproteins are localized within all but the basal cell layer of both tissue types. In buccal cells of primary Sjögren's patients, MUC21 transcripts are down-regulated 3.4-fold and MUC20 2.6-fold. Dysregulation of select epithelial mucins may therefore contribute to xerostomia. CONCLUSIONS: Differential expression of multiple mucins and down-regulation in Sjögren's syndrome support further study of oral epithelial mucin physiology and pathophysiology, including their functions in hydration and lubrication of the oral mucosal pellicle.
29648677 Excess Productivity Costs of Systemic Lupus Erythematosus, Systemic Sclerosis, and Sjögre 2019 Jan OBJECTIVE: To determine excess productivity losses and costs of systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and Sjögren's syndrome (SS) at the population level. METHODS: Administrative databases from the province of British Columbia, Canada, were used to establish population-based cohorts of SLE, SSc, and SS, and matched comparison cohorts were selected from the general population. Random samples from these cohorts were surveyed about time absent from paid and unpaid work and working at reduced levels/efficiency (presenteeism), using validated labor questionnaires. We estimated excess productivity losses and costs of each diagnosis (over and above nonsystemic autoimmune rheumatic diseases [non-SARDs]), using 2-part models and work disability rates (not employed due to health). RESULTS: Surveys were completed by 167 SLE, 42 SSc, and 90 SS patients, and by 375 non-SARDs (comparison group) participants. Altogether, predicted excess hours of paid and unpaid work loss were 3.5, 3.2, and 3.4 hours per week for SLE, SSc, and SS patients, respectively. Excess costs were $86, $69, and $84 (calculated as 2015 Canadian dollars) per week, or $4,494, $3,582, and $4,357 per person annually, respectively. Costs for productivity losses from paid work stemmed mainly from presenteeism (SLE = 69% of costs, SSc = 67%, SS = 64%, and non-SARDs = 53%), not from absenteeism. However, many working-age patients were not employed at all, due to health (SLE = 36%, SSc = 32%, SS = 30%, and non-SARDs = 18%), and the majority of total productivity costs were from unpaid work loss (SLE = 73% of costs, SSc = 74%, SS = 60%, and non-SARDs = 47%). Adjusted excess costs from these unpaid production losses were $127, $100, and $82 per week, respectively, among SLE, SSc, and SS patients. CONCLUSION: In this population-based sample of prevalent SLE, SSc, and SS, lost productivity costs were substantial, mainly from presenteeism and unpaid work impairments.
31507125 Rheumatoid Factors in Hepatitis B and C Infections: Connecting Viruses, Autoimmunity, and 2019 Jul Serum rheumatoid factors are autoantibodies of different isotypes directed against the Fc fraction of immunoglobulin G (IgG) and represent paradigmatic autoantibodies that have been largely used in clinical practice for decades. Traditionally IgG has been associated with rheumatoid arthritis and more recently included also in the classification criteria for SjÓ§gren's syndrome. Researchers have established that rheumatoid factors are positive in a variety of infectious, autoimmune, and neoplastic disorders, thus requiring a comprehensive evaluation of seropositive patients. Of note, hepatitis B and C viruses represent a crossroad that includes the high rheumatoid factor seroprevalence and chronic inflammatory disease, as well as progression to non-Hodgkin's lymphomas. Chronic antigen stimulation is the likely common ground of these processes and rheumatoid factors may represent mere bystanders or drivers of pathology. Mixed cryoglobulinemia and lymphoproliferative disease are prime examples of the deleterious effects of rheumatoid factor-B cell activity, possibly associated with hepatitis B and C. More importantly, they show a clear association in a physiological host response to infection, chronic inflammation, and the slide toward autoimmunity and malignancy. The association between hepatitis B and C infections and the appearance of serum rheumatoid factors is further supported by prevalence data, which support a coexistence of these markers in a significant proportion of cases, with viral infections being frequent causes of rheumatoid factors in patients without a rheumatic condition. We provide a comprehensive overview of the known connections between hepatitis B and C infections and rheumatoid factors.
31413548 Preferences of patients with rheumatoid arthritis regarding disease-modifying antirheumati 2019 BACKGROUND: Although patients have different treatment preferences, these individual preferences could often be grouped in subgroups with shared preferences. Knowledge of these subgroups as well as factors associated with subgroup membership supports health care professionals in the understanding of what matters to patients in clinical decision-making. OBJECTIVES: To identify subgroups of patients with rheumatoid arthritis (RA) based on their shared preferences toward disease-modifying antirheumatic drugs (DMARDs), and to identify factors associated with subgroup membership. METHODS: A discrete choice experiment to determine DMARD preferences of adult patients with RA was designed based on a literature review, expert recommendations, and focus groups. In this multicenter study, patients were asked to state their preferred choice between two different hypothetical treatment options, described by seven DMARD characteristics with three levels within each characteristic. Latent class analyses and multinomial logistic regressions were used to identify subgroups and the characteristics (patient characteristics, disease-related variables, and beliefs about medicines) associated with subgroup membership. RESULTS: Among 325 participating patients with RA, three subgroups were identified: an administration-driven subgroup (45.6%), a benefit-driven subgroup (29.7%), and a balanced subgroup (24.7%). Patients who were currently using biologic DMARDs were significantly more likely to belong to the balanced subgroup than the administration-driven subgroup (relative risk ratio (RRR): 0.50, 95% CI: 0.28-0.89). Highly educated patients were significantly more likely to belong to the benefit-driven subgroup than the balanced subgroup (RRR: 11.4, 95% CI: 0.97-133.6). Patients' medication-related concerns did not contribute significantly to subgroup membership, whereas a near-significant association was found between patients' beliefs about medication necessity and their membership of the benefit-driven subgroup (RRR: 1.12, 95% CI: 1.00-1.23). CONCLUSION: Three subgroups with shared preferences were identified. Only biologic DMARD use and educational level were associated with subgroup membership. Integrating patient's medication preferences in pharmacotherapy decisions may improve the quality of decisions and possibly medication adherence.
31043551 Neutrophil Extracellular Traps May Contribute to the Pathogenesis in Adult-onset Still Dis 2019 Dec OBJECTIVE: Release of neutrophil extracellular traps (NET) has been described as an effector mechanism of polymorphonuclear neutrophils in several inflammatory diseases. Thus, this study was performed to evaluate the role of NET in the pathogenesis of adult-onset Still disease (AOSD). METHODS: We determined the serum levels of NET molecules and investigated their associations with clinical disease activities in patients with AOSD. Further, we analyzed the differences in the NETosis response in AOSD patients compared to healthy controls (HC). To explore the in vivo involvement of NET in AOSD, we performed immunohistochemical analysis of skin and lymph node (LN) biopsies for proteins related to NET in patients with active AOSD. RESULTS: Serum levels of cell-free DNA, myeloperoxidase (MPO)-DNA complex, and α-defensin were significantly increased in patients with AOSD compared to HC. Serum levels of the NET molecules, cell-free DNA, MPO-DNA, and α-defensin were correlated with several disease activity markers for AOSD. In followup of patients with AOSD after treatment with corticosteroid, the levels of cell-free DNA and α-defensin decreased significantly. On immunohistochemistry, neutrophil elastase-positive and MPO-positive inflammatory cells were detected in skin and LN of patients with AOSD, and were expressed in fiber form in the lesions. The serum from patients with active AOSD induced NETosis in neutrophils from HC. NET molecules induced interleukin 1β production in monocytes, representing a novel mechanism in the pathogenesis of AOSD. CONCLUSION: The findings presented here suggest that NET may contribute to the inflammatory response and pathogenesis in AOSD.
30416033 Shared gut, but distinct oral microbiota composition in primary Sjögren's syndrome and sy 2019 Feb OBJECTIVE: Alterations in the microbiota composition of the gastro-intestinal tract are suspected to be involved in the etiopathogenesis of two closely related systemic inflammatory autoimmune diseases: primary Sjögren's syndrome (pSS) and systemic lupus erythematosus (SLE). Our objective was to assess whether alterations in gut and oral microbiota compositions are specific for pSS and SLE. METHODS: 16S ribosomal RNA gene sequencing was performed on fecal samples from 39 pSS patients, 30 SLE patients and 965 individuals from the general population, as well as on buccal swab and oral washing samples from the same pSS and SLE patients. Alpha-diversity, beta-diversity and relative abundance of individual bacteria were used as outcome measures. Multivariate analyses were performed to test associations between individual bacteria and disease phenotype, taking age, sex, body-mass index, proton-pump inhibitor use and sequencing-depth into account as possible confounding factors. RESULTS: Fecal microbiota composition from pSS and SLE patients differed significantly from population controls, but not between pSS and SLE. pSS and SLE patients were characterized by lower bacterial richness, lower Firmicutes/Bacteroidetes ratio and higher relative abundance of Bacteroides species in fecal samples compared with population controls. Oral microbiota composition differed significantly between pSS patients and SLE patients, which could partially be explained by oral dryness in pSS patients. CONCLUSIONS: pSS and SLE patients share similar alterations in gut microbiota composition, distinguishing patients from individuals in the general population, while oral microbiota composition shows disease-specific differences between pSS and SLE patients.