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ID PMID Title PublicationDate abstract
34266986 Impaired Myocardial Flow Reserve on (82)Rubidium Positron Emission Tomography/Computed Tom 2021 Oct OBJECTIVE: To investigate the association between Raynaud phenomenon (RP) and coronary microvascular dysfunction, we measured myocardial flow reserve (MFR) using positron emission tomography/computed tomography (PET/CT) in patients with primary and secondary RP and controls. METHODS: Patients with RP, patient controls, and healthy participants who underwent dynamic rest-stress 82-rubidium PET/CT were studied. Differences in heart rate-blood pressure product-corrected MFR and clinical predictors of reduced MFR (< 2.0) were determined. RESULTS: Forty-nine patients with RP (80% female; aged 65 ± 11 yrs; 11 with primary RP, 18 with systemic sclerosis [SSc], and 20 with other autoimmune rheumatic diseases [AIRDs] including 6 with systemic lupus erythematosus, 6 with rheumatoid arthritis, 4 with overlap syndrome, 2 with Sjögren syndrome, and 2 with inflammatory arthritis), 49 matched patients without RP or AIRD (78% female; 64 ± 13 yrs), and 14 healthy participants (50% female; 35 ± 5 yrs) were studied. Patients with primary RP, matched patient controls, and healthy participants had comparable MFR. Patients with SSc-RP had significantly reduced MFR (1.62 ± 0.32) compared to matched patient controls (P = 0.03, 2.06 ± 0.61) and to healthy participants (P = 0.01, 2.22 ± 0.44). In multivariable logistic regression, SSc was an independent predictor of reduced MFR. We identified a correlation between time since AIRD diagnosis and MFR (r = -0.30, 95% CI -0.63 to -0.02, P = 0.04). CONCLUSION: Our findings suggest that only secondary, not primary, RP is associated with reduced MFR, and that patients with SSc-RP have reduced MFR compared to those with primary RP and patients with other AIRDs. Larger prospective studies are warranted to fully elucidate the prognostic value of MFR in patients with secondary RP.
34155573 Antibody responses after documented COVID-19 disease in patients with autoimmune rheumatic 2021 Nov Patients with autoimmune rheumatic diseases (AIRD) are suspected to have less robust immune responses during COVID-19 due to underlying immune dysfunction and the use of immune-suppressive drugs. Fifty consecutive patients with a diagnosis of AIRD on disease-modifying drugs were included at around 30 days after a confirmatory test for COVID-19. Fifty controls matched one to one for age, sex, and severity of COVID-19 were also included at around 30 days after testing positive for COVID-19. Antibody titers for anti-spike protein IgG and anti-nucleocapsid protein IgG were estimated. Cases (mean age 45.9 ± 13; 76% females) and controls (mean age 45.9 ± 13; 76% females) had similar proportion of comorbidities. Of the cases, 4 had moderate and 1 had severe COVID-19, while 3 and 1 of controls had moderate and severe COVID-19 respectively. Positivity of anti-N IgG was similar between patients (80%) and controls (90%) (p = 0.26). Similarly, anti-S IgG was positive in 82% of patients and 86% of controls (p = 0.79). Both the antibodies were negative in seven (14%) patients and five (10%) of controls (p = 0.76, Fischer exact test). Only anti-N IgG titers were lower in patients as compared to controls. In four patients with rheumatoid arthritis, two with spondyloarthritis and one with eosinophilic fasciitis both antibodies were not detectable. They did not differ from the rest of the cohort in clinical characteristics. The patients with AIRD had adequate protective antibody responses to COVID-19 at a median of 30 days post-infection. Thus, the presence of AIRD or the use of immunosuppressants does not seem to influence the development of humoral immune response against COVID-19. Key Points • Patients with autoimmune rheumatic diseases (AIRD) are suspected to have less robust immune responses. • In our cohort of 50 patients with AIRD with confirmed COVID-19, only seven did not have detectable protective antibodies at 30 days post infection. • Patients with AIRD on immunosuppressants have adequate protective antibodies post COVID-19 disease, at rates similar to that in health controls.
34511099 Patients' risk factors for periprosthetic joint infection in primary total hip arthroplast 2021 Sep 12 BACKGROUND: Periprosthetic joint infection (PJI) is a catastrophic complication after total hip arthroplasty (THA). Our meta-analysis aimed to identify the individual-related risk factors that predispose patients to PJI following primary THA. METHODS: Comprehensive literature retrieval from Pubmed, Web of Science, and the Cochrane Library was performed from inception to Feb 20th, 2021. Patient-related risk factors were compared as per the modifiable factors (BMI, smoke and alcohol abuse), non-modifiable factors (gender, age), and medical history characteristics, such as diabetes mellitus (DM), avascular necrosis (AVN) of femoral head, femoral neck fracture, rheumatoid arthritis (RA), cardiovascular disease (CVD), and osteoarthritis (OA) etc. The meta-analysis was applied by using risk ratios with 95% corresponding intervals. Sensitivity analysis and publication bias were performed to further assess the credibility of the results. RESULTS: Overall, 40 studies with 3,561,446 hips were enrolled in our study. By implementing cumulative meta-analysis, higher BMI was found associated with markedly increased PJI risk after primary THA [2.40 (2.01-2.85)]. Meanwhile, medical characteristics including DM [1.64 (1.25-2.21)], AVN [1.65 (1.07-2.56)], femoral neck fracture [1.75 (1.39-2.20)], RA [1.37 (1.23-1.54)], CVD [1.34 (1.03-1.74)], chronic pulmonary disease (CPD) [1.22 (1.08-1.37)], neurological disease [1.19 (1.05-1.35)], opioid use [1.53 (1.35-1.73)] and iron-deficiency anemia (IDA) [1.15 (1.13-1.17)] were also significantly correlated with higher rate of PJI. Conversely, dysplasia or dislocation [0.65 (0.45-0.93)], and OA [0.70 (0.62-0.79)] were protective factors. Of Note, female gender was protective for PJI only after longer follow-up. Besides, age, smoking, alcohol abuse, previous joint surgery, renal disease, hypertension, cancer, steroid use and liver disease were not closely related with PJI risk. CONCLUSION: Our finding suggested that the individual-related risk factors for PJI after primary THA included high BMI, DM, AVN, femoral neck fracture, RA, CVD, CPD, neurological disease, opioid use and IDA, while protective factors were female gender, dysplasia/ dislocation and OA.
33087256 Natural Killer Cell Transcript 4 promotes the development of Sjӧgren's syndrome via activ 2021 Jan Autoimmune disorders are the third most common diseases in the United States, and affect the daily lives of millions of people. In this study, we analyzed patient samples, utilized a transgenic mouse model and human B cells to reveal Natural Killer Cell Transcript 4 (NK4) as a novel regulator that promotes the development of autoimmune disorders. NK4 was significantly elevated in samples from patients with Sjӧgren's Syndrome (SS). SS patients show elevated NK4 levels. There is a strong and positive correlation between the increased levels of NK4 and the duration of SS. Interestingly, transgenic expression of NK4 in a mouse model led to the development of autoantibodies and lymphocytic infiltration in salivary glands similar to those in SS patients. Those phenotypes were associated with increased B1a cells in the peritoneum, plasma cells in the spleen, and increased IgM, IgA, and IgG2a in serum of the NK4 transgenic mice. The autoimmune phenotypes became more severe in older mice. Moreover, after NK4 transfection, human naïve B cells were activated and memory B cells differentiation into IgG and IgA-plasmablasts, resulting in an increased production of autoantibodies.NK4 regulated the differentiation and activation of B cells through activating Rap1 activity. NK4 also promoted B cell migration in a paracrine fashion through an induction of CXCL13 in endothelial cells. Collectively, these findings identify NK4 as a promoter of the development of autoimmune disorders through its roles on B cells. Therefore, NK4 may be a novel therapeutic target for the treatment of autoimmune diseases.
33441481 Outcomes of atrial fibrillation hospitalizations in patients with systemic lupus erythemat 2021 Jan 13 This study compares outcomes of patients admitted for atrial fibrillation (AF) with and without coexisting systemic lupus erythematosus (SLE). The primary outcome was inpatient mortality. Hospital length of stay (LOS), total hospital charges, odds of undergoing ablation, pharmacologic cardioversion and electrical cardioversion were secondary outcomes of interest. Data were abstracted from the National Inpatient Sample (NIS) 2016 and 2017 database. The NIS was searched for adult hospitalizations with AF as principal diagnosis with and without SLE as secondary diagnosis using International Classification of Diseases, Tenth Revision, Clinical Modification codes. Multivariate logistic and linear regression analysis was used accordingly to adjust for confounders. There were over 71 million discharges included in the combined 2016 and 2017 NIS database. 821,630 hospitalizations were for adult patients, who had a principal diagnosis of AF, out of which, 2645 (0.3%) had SLE as secondary diagnosis. Hospitalizations for AF with SLE had similar inpatient mortality (1.5% vs 0.91%, adjusted OR (AOR): 1.0, 95% CI 0.47 to 2.14, p=0.991), LOS (4.2 vs 3.4 days, p=0.525), total hospital charges ($51,351 vs $39,121, p=0.056), odds of undergoing pharmacologic cardioversion (0.38% vs 0.38%, AOR: 0.90, 95% CI 0.22 to 3.69, p=0.880) and electrical cardioversion (12.9% vs 17.5%, AOR 0.87, 95% CI 0.66 to 1.15, p=0.324) compared with those without SLE. However, SLE group had increased odds of undergoing ablation (6.8% vs 4.2%, AOR: 1.9, 95% CI 1.3 to 2.7, p<0.0001). Patients admitted for AF with SLE had similar inpatient mortality, LOS, total hospital charges, likelihood of undergoing pharmacologic and electrical cardioversion compared with those without SLE. However, SLE group had greater odds of undergoing ablation.
33508522 Acute Seymour fractures in children/adolescents overlooked as a simple nail injury: Reduct 2021 Apr We retrospectively report the outcomes of several cases in which acute Seymour fractures were treated by open reduction of displaced distal bony fragments with concurrent nail repair, following complete incision and drainage without K-wire fixation. Among 21 patients surgically treated between March 2004 and December 2018, the final 12 were evaluated after at least 2 years of follow-up. All children/adolescents presented more than 24 h after the injury. All injuries were unreduced in the emergency department, with typical features of skin disruption around the eponychium/perionychium. Reduction was maintained without a K-wire after repairing the bone-periosteum-nail bed-nail plate of the distal fragment and the corresponding physis-periosteum-germinal matrix-proximal nail-fold of the proximal stump. Dorsal angulation, finger length, postoperative pain on visual analog scale (VAS), Disabilities of the Arm, Shoulder, and Hand (DASH) score, and active range of motion (ROM) were evaluated at the final follow-up. The mean patient age was 9.3 years (range, 3-13 years) and the mean time from injury to surgery was 35 h (range, 28-44 h). Only one child suffered a superficial infection; however, it resolved with 1 week of oral antibiotic treatment. At the final follow-up, mean dorsal angulation was 0.50° ± 1.24°; the length ratio compared with the corresponding contralateral phalanx was 98% (both, P >  0.05). The final pain on VAS, DASH score, and ROM ratio were 0.25 ± 0.45, 0.83 ± 1.34, and 99 ± 2%, respectively. Unreduced Seymour fractures presenting more than 24 h after the injury were treated by proper debridement and reduction of the fracture without the use of a K-wire. However, to determine whether the infection rate is definitively lower, this procedure should be compared with the conventional procedure using a K-wire. Level of Evidence: Therapeutic level IV.
33268076 Factors predictive for union of basal fracture of the ulnar styloid process after distal r 2021 Mar BACKGROUND: Some basal ulnar styloid fractures (USFs) achieve union without surgical fixation when accompanying distal radius fractures (DRFs) are treated via placement of volar locking plates (VLPs). The purpose of this study was to seek factors predictive of such healing through the retrospective case-control study. METHODS: We evaluated 203 patients who received VLPs to treat DRFs in our institute from March 2010 to February 2018; Group 1 contained "union" patients and Group 2 contained "nonunion" patients. Basic demographic, radiological, and operative variables were compared. At the final follow-up (at least 2 years postoperatively), pain was scored using a visual analog scale (VAS). Scores on the Disabilities of the Arm, Shoulder, and Hand (DASH) instrument; grip strengths; and demerit points of the Gartland and Werley system were compared between groups. RESULTS: Group 1 consisted of 58 patients and Group 2 consisted of 147 patients. Univariate analysis showed that age, bone mineral density (BMD), and Gaulke USF classification significantly differed between groups (all p < 0.05). Multivariate analysis showed that BMD (p < 0.001, odds ratio [OR] = 0.214, 95% confidence interval [95% CI] = 0.126-0.363) and Gaulke classification (p < .001, OR = 0.092, 95% CI = 0.034-0.250) were significantly associated with USF union, which was significantly higher in patients with mean BMD ≥ -0.12 (the cutoff value) and type IIC USFs. However, postoperative clinical outcomes at the final follow-up did not differ significantly between groups (all p > 0.05). CONCLUSIONS: Approximately 30% (58/205) of basal USFs associated with DRFs united after VLPs alone were placed to treat the DRFs. BMD ≥ -0.12 independently predicted union. Type IIC USFs exhibited more union than other fracture types. Additional surgical fixation of a basal USF accompanied by a DRF treated via VLP placement may be unnecessary, especially if BMD is good and fracture type is IIC. LEVEL OF EVIDENCE: Level III, Case-control study.
33446013 MicroRNA-146a-5p enhances T helper 17 cell differentiation via decreasing a disintegrin an 2021 Dec In clinical practice, we found that microRNA (miR)-146a-5p is significantly up-regulated in peripheral blood mononuclear cells (PBMCs) of primary sjögren's syndrome (pSS) patients. In vitro experiments confirmed that miR-146a-5p promotes T helper 17 (Th17) cell differentiation, but the specific mechanism is still unknown. To solve this problem, 20 pSS patients and 20 healthy subjects were enrolled in this study and PBMCs were isolated from their blood. The expression of the membrane IL-23 R (mIL-23 R) in PBMCs was determined. CD3(+) T cells were also isolated and used to further analyze the relationship between the ectodomain shedding of mIL-23 R and a disintegrin and metalloprotease 17 (ADAM17). Finally, miR-146a-5p inhibitor and mimics were transfected into PBMCs to evaluate the relationship between ADAM17 and mIL-23 R, and explore the role of mIL-23 R and ADAM17 in Th17 cell differentiation. Our results revealed a significantly increased expression of miR-146a-5p in PBMCs from pSS patients and significantly increased percentage of Th17 cells compared to PBMCs from healthy controls. Under polarization culture conditions, pSS patient-derived PBMCs can more easily differentiate into Th17 cells, which was, to a great extent, attributable to the increased expression of mIL-23 R. Moreover, ADAM17, an ectodomain sheddase of mIL-23 R, was targeted and negatively regulated by miR-146a-5p, which reduced the ectodomain shedding of mIL-23 R. Overall, our results suggested that miR-146a-5p could promote Th17 cell differentiation through targeting and negatively regulating ADAM17. Thus, these results might offer a new approach in the treatment of pSS.
34936548 Real-life golimumab persitence in patients with axial spondyloarthritis: post-hoc results 2021 Dec 22 OBJECTIVES: To evaluate in clinical practice the persistence and safety of golimumab, together with the evolution of disease activity and patient reported outcomes, in adult patients with rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis (axSpA). This article focuses on the outcomes of golimumab treatment in axSpA patients. METHODS: Golimumab persistence 24 months after initial prescription (primary outcome) was assessed using Kaplan-Meier estimates. Secondary outcomes included evaluations of disease activity evolution (ASDAS and BASDAI), patient-reported outcomes (EQ-5D, SF-12 and HAQ), and golimumab's safety profile. RESULTS: Of 478 axSpA patients, 60.9% were biologic-naïve. Mean age and proportion of females were higher in biologics-pretreated patients (46.8 vs. 40.2 years, p<0.001 and 62.0% vs. 49.8%, p=0.009, respectively). Golimumab persistence at 24 months was 52.6% [95% CI 47.9-57.1%] in the axSpA cohort. It was 59.2% [95% CI 53.1-64.8%] and 42.7% [95% CI 35.3-49.8%] respectively, for biologics-naïve and biologics-pretreated patients (p<0.01), and 65.9% [95% CI 58.9-72.0%] and 41.5% [95% CI 35.2-47.6%], respectively for males and females (p<0.01). Reasons for golimumab discontinuation were primary non-response (37.4%), secondary non-response (24.8%) and intolerance (21.5%). Disease activity and patient reported outcomes improved significantly for those who persisted at 24 months and were higher for biologics-naïve patients. CONCLUSIONS: Golimumab persistence at 2 years in axSpA patients was 52.6%. Previous treatment with another biologic and female gender were associated with earlier discontinuation. Golimumab was a well-tolerated therapy for axSpA, with no new safety signals observed.
34539627 Mitochondria in Injury, Inflammation and Disease of Articular Skeletal Joints. 2021 Inflammation is an important biological response to tissue damage caused by injury, with a crucial role in initiating and controlling the healing process. However, dysregulation of the process can also be a major contributor to tissue damage. Related to this, although mitochondria are typically thought of in terms of energy production, it has recently become clear that these important organelles also orchestrate the inflammatory response via multiple mechanisms. Dysregulated inflammation is a well-recognised problem in skeletal joint diseases, such as rheumatoid arthritis. Interestingly osteoarthritis (OA), despite traditionally being known as a 'non-inflammatory arthritis', now appears to involve an element of chronic inflammation. OA is considered an umbrella term for a family of diseases stemming from a range of aetiologies (age, obesity etc.), but all with a common presentation. One particular OA sub-set called Post-Traumatic OA (PTOA) results from acute mechanical injury to the joint. Whether the initial mechanical tissue damage, or the subsequent inflammatory response drives disease, is currently unclear. In the former case; mechanobiological properties of cells/tissues in the joint are a crucial consideration. Many such cell-types have been shown to be exquisitely sensitive to their mechanical environment, which can alter their mitochondrial and cellular function. For example, in bone and cartilage cells fluid-flow induced shear stresses can modulate cytoskeletal dynamics and gene expression profiles. More recently, immune cells were shown to be highly sensitive to hydrostatic pressure. In each of these cases mitochondria were central to these responses. In terms of acute inflammation, mitochondria may have a pivotal role in linking joint tissue injury with chronic disease. These processes could involve the immune cells recruited to the joint, native/resident joint cells that have been damaged, or both. Taken together, these observations suggest that mitochondria are likely to play an important role in linking acute joint tissue injury, inflammation, and long-term chronic joint degeneration - and that the process involves mechanobiological factors. In this review, we will explore the links between mechanobiology, mitochondrial function, inflammation/tissue-damage in joint injury and disease. We will also explore some emerging mitochondrial therapeutics and their potential for application in PTOA.
33616791 Sexual and mental health of woman suffering from selected connective tissue diseases: an o 2021 Aug OBJECTIVES: The aim of the study was to assess the sexual and mental health of women suffering from connective tissue diseases and to determine the potential interrelationships between the studied clinical variables and sexual and mental health. METHODS: The study was conducted in a group of women with connective tissue diseases. To assess somatic health, we used The Health Assessment Questionnaire (HAQ-DI), and to assess sexual health, we used the Female Sexual Function Index (FSFI) and Sexual Satisfaction Questionnaire (KSS). The mental health was assessed by using the Hospital Anxiety and Depression Scale (HADS-M) and the PERMA-Profiler (PL). RESULTS: The study involved 81 women suffering from connective tissue diseases, especially rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS) and juvenile idiopathic arthritis (JIA). Clinical symptoms of sexual dysfunction were observed in 54% women. The biggest difficulties occur in sexual desire, orgasm and arousal. Patients had symptoms of anxiety and depressive disorders. Higher levels of anxiety and depression are associated with poorer overall sexual functioning and better overall sexual functioning, and all its dimensions are associated with a higher level of mental well-being. There was also an observed relationship with the functional limitation due to pain and duration of the disease. CONCLUSION: The study confirms the existence of difficulties in the sexual functioning of women suffering from connective tissue diseases and shows the relationship between sexual and mental health and basic disease. The observed relationships are important information in the treatment and medical care of people with this group of rheumatic diseases. Key Points • The article presents one of the few studies about sexual functioning of Polish population women with connective tissue diseases. • The aim was to assess the sexual and mental health of women with various connective tissue diseases and determine the potential interrelationships between the clinical variables and sexual and mental health. • The study confirms difficulties in the sexual functioning of women with connective tissue diseases. The biggest difficulties occur in sexual desire, orgasm and arousal. Patients also had mental disorders symptoms. • The study presents conclusions and indications which may be important and help specialists approach the treatment process in an interdisciplinary way.
33420722 The impact of autoimmune systemic inflammation and associated medications on male reproduc 2021 May Autoimmune disorders currently affect 5%-8% of the global population, characterized by an aberrant chronic inflammatory response to self-antigens. The aim of this study was to systematically review the current available evidence investigating the impact of systemic autoimmune diseases and associated immunosuppressive treatment on fertility parameters of adult men. Clinical trials, observational studies, and case reports written in English and reporting semen analysis, evaluation of seminal oxidative stress, and/or sperm DNA fragmentation in patients affected by psoriasis and psoriatic arthritis, celiac disease, inflammatory bowel diseases, systemic lupus erythematosus, ankylosing spondylitis, hidradenitis suppurativa, uveitis, dermatomyositis, and rheumatoid arthritis were collected by searching on PubMed, EMBASE, OVID, Scopus, and Cochrane Library databases, with no limit of time. The study quality and the extent of bias in design, methods, and outcome assessment were evaluated by applying the Joanna Briggs Institute Critical Appraisal tools. Evidence suggested that various autoimmune diseases or relevant medications can adversely affect male fertility parameters and that patients may benefit of counseling and sperm cryopreservation. Clinical trials further investigating any adverse effect of autoimmunity and related thereby on male infertility are warranted, to develop appropriate guidelines for males diagnosed and treated for autoimmune disorders.
33319166 Transcriptional response modules characterize IL-1β and IL-6 activity in COVID-19. 2021 Jan 22 Dysregulated IL-1β and IL-6 responses have been implicated in the pathogenesis of severe Coronavirus Disease 2019 (COVID-19). Innovative approaches for evaluating the biological activity of these cytokines in vivo are urgently needed to complement clinical trials of therapeutic targeting of IL-1β and IL-6 in COVID-19. We show that the expression of IL-1β or IL-6 inducible transcriptional signatures (modules) reflects the bioactivity of these cytokines in immunopathology modelled by juvenile idiopathic arthritis (JIA) and rheumatoid arthritis. In COVID-19, elevated expression of IL-1β and IL-6 response modules, but not the cytokine transcripts themselves, is a feature of infection in the nasopharynx and blood but is not associated with severity of COVID-19 disease, length of stay, or mortality. We propose that IL-1β and IL-6 transcriptional response modules provide a dynamic readout of functional cytokine activity in vivo, aiding quantification of the biological effects of immunomodulatory therapies in COVID-19.
33208344 Anti-centromere antibodies target centromere-kinetochore macrocomplex: a comprehensive aut 2021 May OBJECTIVES: Anti-centromere antibodies (ACAs) are detected in patients with various autoimmune diseases such as Sjögren's syndrome (SS), systemic sclerosis (SSc) and primary biliary cholangitis (PBC). However, the targeted antigens of ACAs are not fully elucidated despite the accumulating understanding of the molecular structure of the centromere. The aim of this study was to comprehensively reveal the autoantigenicity of centromere proteins. METHODS: A centromere antigen library including 16 principal subcomplexes composed of 41 centromere proteins was constructed. Centromere protein/complex binding beads were used to detect serum ACAs in patients with SS, SSc and PBC. ACA-secreting cells in salivary glands obtained from patients with SS were detected with green fluorescent protein-fusion centromere antigens and semiquantified with confocal microscopy. RESULTS: A total of 241 individuals with SS, SSc or PBC and healthy controls were recruited for serum ACA profiling. A broad spectrum of serum autoantibodies was observed, and some of them had comparative frequency as anti-CENP-B antibody, which is the known major ACA. The prevalence of each antibody was shared across the three diseases. Immunostaining of SS salivary glands showed the accumulation of antibody-secreting cells (ASCs) specific for kinetochore, which is a part of the centromere, whereas little reactivity against CENP-B was seen. CONCLUSIONS: We demonstrated that serum autoantibodies target the centromere-kinetochore macrocomplex in patients with SS, SSc and PBC. The specificity of ASCs in SS salivary glands suggests kinetochore complex-driven autoantibody selection, providing insight into the underlying mechanism of ACA acquisition.
34763722 No increased risk of Alzheimer's disease among people with immune-mediated inflammatory di 2021 Nov 12 OBJECTIVE: Immune-mediated inflammatory diseases (IMID) are characterized by systemic inflammation affecting the joints and bodily organs. Studies examining the association between individual IMIDs and the risk of Alzheimer's disease (AD) have yielded inconsistent findings. This study examines AD risk across a group of IMIDs in a large population-based sample of older adults. METHODS: Data on a national sample of US adults over age 50 was drawn from the Health and Retirement Study (HRS) and linked Medicare claims from 2006 to 2014. IMIDs include rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, and related conditions. We identified IMIDs from 2006 to 2009 Medicare claims using International Classification of Diseases (ICD9-CM) codes. The date of incident AD was derived from Chronic Conditions Warehouse (CCW) identifiers. We examined the risk of AD from 2009 to 2014 using Cox proportional hazards models, both unadjusted and adjusted for age, gender, education, race, and the genetic risk factor APOE-e4. RESULTS: One hundred seventy-one (6.02%) of the 2842 total HRS respondents with Medicare coverage and genetic data were classified with IMIDs. Over the subsequent 6 years, 9.36% of IMID patients developed AD compared to 8.57% of controls (unadjusted hazard ratio (HR): 1.09, 95% CI .66-1.81, p = 0.74). Adjusted HR 1.27 (95% CI 0.76-2.12, p = 0.35). Age (HR for 10-year increment 3.56, p < .001), less than high school education (HR 1.70, p = .007), and APOE-e4 (HR 2.61, p < .001 for one or two copies), were also statistically significant predictors of AD. CONCLUSION: HRS respondents with common IMIDs do not have increased risk of Alzheimer's disease over a 6-year period.
33556668 Leflunomide ameliorates experimental autoimmune myasthenia gravis by regulating humoral an 2021 Apr Leflunomide, an immunosuppressive disease-modifying anti-rheumatic drug (DMARD), is widely used in the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PA) as well as multiple sclerosis. However, its role in myasthenia gravis (MG) has not yet been clearly explored. Here, we investigated the effect of leflunomide on experimental autoimmune myasthenia gravis (EAMG) in vivo and in vitro. The results demonstrated that leflunomide alleviated the severity of EAMG associated with reduced serum total anti-acetylcholine receptor (AChR) IgG levels. During the development of EAMG, the increase of follicular helper T cells (Tfh) 1, Tfh 17 cells and decrease of follicular regulatory T cells (Tfr) were reversely altered after leflunomide administration. Our work further found that leflunomide might inhibit Tfh cells through the IL-21/STAT3 pathway to reduce the secretion of antibodies by B cells. In addition, leflunomide rebuilt the balance of Th1/Th2/Th17/Treg subsets. These results suggested that leflunomide ameliorated EAMG severity by regulating humoral immune responses and Th cell profiles thereby providing a novel effective treatment strategy for MG.
35056521 Analyzing the Role of Gut Microbiota on the Onset of Autoimmune Diseases Using TNF(ΔARE) 2021 Dec 30 Very little is known about disease transmission via the gut microbiome. We hypothesized that certain inflammatory features could be transmitted via the gut microbiome and tested this hypothesis using an animal model of inflammatory diseases. Twelve-week-old healthy C57 Bl/6 and Germ-Free (GF) female and male mice were fecal matter transplanted (FMT) under anaerobic conditions with TNF(ΔARE-/+) donors exhibiting spontaneous Rheumatoid Arthritis (RA) and Inflammatory Bowel Disease (IBD) or with conventional healthy mice control donors. The gut microbiome analysis was performed using 16S rRNA sequencing amplification and bioinformatics analysis with the HIVE bioinformatics platform. Histology, immunohistochemistry, ELISA Multiplex analysis, and flow cytometry were conducted to confirm the inflammatory transmission status. We observed RA and IBD features transmitted in the GF mice cohort, with gut tissue disruption, cartilage alteration, elevated inflammatory mediators in the tissues, activation of CD4/CD8+ T cells, and colonization and transmission of the gut microbiome similar to the donors' profile. We did not observe a change or transmission when conventional healthy mice were FMT with TNF(ΔARE-/+) donors, suggesting that a healthy microbiome might withstand an unhealthy transplant. These findings show the potential involvement of the gut microbiome in inflammatory diseases. We identified a cluster of bacteria playing a role in this mechanism.
34335573 Targeting Tristetraprolin Expression or Functional Activity Regulates Inflammatory Respons 2021 The RNA-binding protein tristetraprolin (TTP) is an anti-inflammatory factor that prompts the mRNA decay of target mRNAs and is involved in inflammatory diseases such as rheumatoid arthritis (RA). TTP is regulated by phosphorylation, and protein phosphatase 2A (PP2A) can dephosphorylate TTP to activate its mRNA-degrading function. Some small molecules can enhance PP2A activation. Short interfering RNA (siRNA) targeting TTP expression or PP2A agonist (Arctigenin) was administered to monosodium urate (MSU) crystal-induced J774A.1 cells, and the expression of inflammatory related genes was detected by RT-PCR and Western blot assays. The effects of Arctigenin in mouse models of acute inflammation induced by MSU crystals, including peritonitis and arthritis, were evaluated. The data indicated that TTP expression levels and endogenous PP2A activity were increased in MSU-crystal treated J774A.1 cells. TTP knockdown exacerbated inflammation-related genes expression and NLRP3 inflammasome activation. However, PP2A agonist treatment (Arctigenin) suppressed MSU crystal-induced inflammation in J774A.1 cells. Arctigenin also relieved mitochondrial reactive oxygen species (mtROS) production and improved lysosomal membrane permeability in MSU crystal-treated J774A.1 cells. Moreover, TTP knockdown reversed the anti-inflammatory and antioxidant effects of Arctigenin. Oral administration of Arctigenin significantly alleviated foot pad swelling, the number of inflammatory cells in peritoneal lavage fluids and the production of IL-1β in the mouse model of inflammation induced by MSU crystals. Collectively, these data imply that targeting TTP expression or functional activity may provide a potential therapeutic strategy for inflammation caused by MSU crystals.
34224936 New developments implicating IL-21 in autoimmune disease. 2021 Aug Elevated interleukin (IL)-21 is a common finding in the tissues and/or sera of patients with autoimmune disease. CD4 T cells are the primary producers of IL-21; often the IL-21 producing CD4 T cells will express molecules associated with follicular helper cells (T(FH)). Recent work has shown that the CD4 T cell-derived IL-21 is able to promote effector functions and memory differentiation of CD8 T cells in chronic infections and cancer. Autoimmunity has similarities to chronic infections and cancer. However, CD4 T cell-derived IL-21:IL21R signaling in CD8 T cells has not been fully appreciated in the context of autoimmunity. In this review, we assess the current knowledge regarding CD4 T cell-derived IL-21 and IL21R signaling within CD8 T cells and evaluate what implications it has within several autoimmune diseases including systemic lupus erythematous, rheumatoid arthritis, juvenile idiopathic arthritis, type 1 diabetes mellitus, psoriasis, Sjögren's syndrome, vitiligo, antiphospholipid syndrome, pemphigus, and giant cell arteritis.
33323531 Improving Pneumococcal Vaccination Rates in Rheumatology Patients by Using Best Practice A 2021 Sep OBJECTIVE: To improve pneumococcal vaccination (PV) rates among rheumatology clinic patients on immunosuppressive therapy in the outpatient settings. METHODS: This quality improvement project was based on the pre-post intervention design. Phase I of the project targeted patients with rheumatoid arthritis from 13 rheumatology clinics (January 2013-July 2015) on immunosuppressive therapy to receive the pneumococcal polysaccharide vaccine (PPSV23). In the Phase II study (January 2016-October 2017), all patients on immunosuppressive medications regardless of diagnosis were targeted to receive PPSV23 and the pneumococcal conjugate vaccine (PCV13). The best practice alerts (BPAs) for both PVs were developed based on the Centers for Disease Control and Prevention guidelines, which appeared on electronic medical records for eligible patients at the time of assessment by the medical assistant. The BPA was designed to inform the vaccination status and enable the physician to order the PV, or to document refusal or deferral reasons. Education regarding vaccine guidelines, BPAs, vaccination process, and regular feedback of results were important project interventions. The vaccination rates during pre-post intervention for each study phase were compared using chi-square test. RESULTS: During phase I, PPSV23 vaccination rates improved from a 28% preintervention rate to 61.5% (P < 0.0001). During phase II, 77.4% of patients had received either PPSV23, PCV13, or both, compared to 49.6% of patients in the preintervention period (P < 0.0001). The documentation rates (vaccine received, ordered, patient refusal and deferral reasons) increased significantly in both phases. CONCLUSION: Electronic identification of vaccine eligibility and implementation of BPAs with capabilities to order and document resulted in significantly improved PV rates. The process has potential for self-sustainability and generalizability.