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ID PMID Title PublicationDate abstract
33795164 Necrotic Ulceration of the Hand Case Review: Think Beyond Infection. 2021 May Neutrophilic dermatosis of the dorsal hands is a rare neutrophilic dermatosis that can be associated with inflammatory bowel disease, rheumatoid arthritis, and underlying malignancies. The occurrence of trauma as an initiating factor and its early features of pain and inflammation followed by blistering or ulceration mean that it can be mistaken for necrotizing infection. Neutrophilic dermatosis of the dorsal hands should be considered in all patients who present with such features confined to the back of the hands, particularly those with negative microbiological results or lack of response to antibiotic therapy. A case review design was used to analyze the presentation of a woman aged 65 years in the United Kingdom, seeking care for a painful rash on the hand in the emergency department that was subsequently diagnosed as neutrophilic dermatosis of the dorsal hands. Emergency clinician awareness of neutrophilic dermatosis of the dorsal hands as a rare differential diagnosis for patients presenting with necrotic ulceration may prevent unnecessary antibiotic therapy and surgical intervention.
33681167 Update on Nanoparticle-Based Drug Delivery System for Anti-inflammatory Treatment. 2021 Nanobiotechnology plays an important role in drug delivery, and various kinds of nanoparticles have demonstrated new properties, which may provide opportunities in clinical treatment. Nanoparticle-mediated drug delivery systems have been used in anti-inflammatory therapies. Diseases, such as inflammatory bowel disease, rheumatoid arthritis, and osteoarthritis have been widely impacted by the pathogenesis of inflammation. Efficient delivery of anti-inflammatory drugs can reduce medical dosage and improve therapeutic effect. In this review, we discuss nanoparticles with potential anti-inflammatory activity, and we present a future perspective regarding the application of nanomedicine in inflammatory diseases.
33589100 Managing Cardiovascular Risk in Patients with Rheumatic Disease. 2021 Mar Individuals with rheumatoid arthritis, systemic lupus erythematosus, or gout have increased risk of cardiovascular disease (CVD) compared with the general population. This risk relates to a combination of traditional cardiovascular risk factors and disease-specific factors. Screening for CVD is important because CVD contributes to significant morbidity and mortality. Management includes tight control of disease activity to reduce inflammation, but with care to minimize use of nonsteroidal anti-inflammatory drugs and prolonged courses of high-dose corticosteroids. Traditional cardiovascular risk factors should be managed with a combination of lifestyle interventions and pharmacotherapy. The decision to start antihypertensive and lipid-lowering therapy should be based on individual CVD risk.
34630616 Network Pharmacology-Based Analysis on the Curative Effect of Kunxian Capsules against Rhe 2021 Kunxian capsules (KCs), a Chinese patent medicine, have been clinically proven to be effective in the treatment of rheumatoid arthritis (RA). However, the chemical profile of KC remains to be characterized, and the mechanism underlying the protective effect against RA is yet to be elucidated. Here, a network pharmacology-based approach was adopted, integrated with the chemical profiling of KC by UHPLC-Q-TOF/MS. As a result, a total of 67 compounds have been identified from KC extract, among which 43 were authenticated by comparison to the mass spectrum of standard chemicals. ADME behaviors of the chemical constituents of KC were predicted, resulting in 35 putative active ingredients. Through target prediction of both active ingredients of KC and RA and PPI analysis, core targets were screened out, followed by biological process and related pathway enrichment. Then, a TCM-herb-ingredient-target-pathway network was constructed and a multicomponent, multitarget, and multipathway synergistic mechanism was proposed, providing an information basis for further investigation. The active pharmaceutical ingredients included mainly terpenoids (such as triptolide and celastrol), sesquiterpene pyridines (such as wilforgine and wilforine), and flavonoids (such as icariin, epimedin A, B, and C, and 2″-O-rhamnosylicariside II).
34106218 Association of Granuloma Annulare With Type 2 Diabetes, Hyperlipidemia, Autoimmune Disorde 2021 Jul 1 IMPORTANCE: Although granuloma annulare (GA) has been associated with several other conditions, these studies have been limited by single-center designs and small sample sizes. OBJECTIVE: To evaluate whether there is an association between GA and type 2 diabetes, hyperlipidemia, autoimmune conditions, and hematologic malignant neoplasms, using a large population-based cohort study. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study conducted between January 1, 2016, and June 30, 2019, used deidentified data from the US Optum Clinformatics Data Mart Database. A total of 5137 patients with GA were matched by age and sex with up to 10 randomly selected controls (n = 51 169) with a diagnosis of a nevus or seborrheic keratosis. MAIN OUTCOMES AND MEASURES: Logistic regression was used to evaluate for potential associations between GA and diabetes, hyperlipidemia, autoimmune conditions, and hematologic malignant neoplasms. All analyses were adjusted for race/ethnicity, income, and educational level. RESULTS: This study included 5137 individuals with GA (3760 women [73.2%]; mean [SD] age, 57.7 [19.0] years) and 51 169 controls (37 456 women [73.2%]; mean [SD] age, 57.7 [19.0] years). Those with GA were more likely than controls to have baseline diabetes (1086 [21.1%] vs 6780 [13.3%]; adjusted odds ratio [aOR], 1.67; 95% CI, 1.55-1.80), hyperlipidemia (1669 [32.5%] vs 14 553 [28.4%]; aOR, 1.15; 95% CI, 1.08-1.23), hypothyroidism (727 [14.2%] vs 5780 [11.3%]; aOR, 1.24; 95% CI, 1.15-1.36), and rheumatoid arthritis (62 [1.2%] vs 441 [0.9%]; aOR, 1.34; 95% CI, 1.02-1.75). Those with GA were more likely to have incident diabetes (144 [2.8%] vs 1061 [2.1%]; aOR, 1.31; 95% CI, 1.10-1.57), hypothyroidism (41 [0.8%] vs 252 [0.5%]; aOR, 1.59; 95% CI, 1.14-2.22), systemic lupus erythematosus (21 [0.4%] vs 65 [0.1%]; aOR, 3.06; 95% CI, 1.86-5.01), and rheumatoid arthritis (26 [0.5%] vs 122 [0.2%]; aOR, 2.05; 95% CI, 1.34-3.13). There was no association between GA and an increased risk of hematologic malignant neoplasms. CONCLUSIONS AND RELEVANCE: This population-based cohort study identified associations between GA and baseline diabetes and hyperlipidemia as well as between GA and both baseline and incident autoimmune conditions. These findings suggest that diabetes and hyperlipidemia may be risk factors for the development of GA and that autoimmunity may be an important factor in the pathogenesis of GA.
33779079 Decreased Levels of STAT1 and Interferon-γ-Induced STAT1 Phosphorylation in Rheumatoid Ar 2021 Apr OBJECTIVE: We investigated whether a previously reported association of IFNGR expression with rheumatoid arthritis (RA) and its radiographic severity reflects differences in proximal interferon-γ (IFN-γ) signaling in T cells from patients with RA compared with healthy controls (HC). METHODS: Using phosphoflow cytometry, we compared IFN-γ-stimulated signal transducer and activator of transcription 1 (STAT1) activation in CD4(+) and CD8(+) T-cell populations from patients with RA and HC. RESULTS: Compared with controls, patients with RA had a higher proportion of CD4(+) T cells, associated with expansion of the CD4(+) effector memory subset. Several CD4(+) T-cell types exhibited reduced IFN-γ-induced phosphoSTAT1(Y701) (pSTAT1(Y701) ) in patients with RA compared with HC. Engaging the T-cell receptor (TCR) complex on CD4(+) T cells during IFN-γ stimulation abrogated the reduction in STAT1 activation in patients with RA but had no effect in HC. The phosphorylation of STAT1(S727) was similar in CD4(+) T cells from patients with RA and HC. In contrast to CD4(+) T cells, IFN-γ-induced pSTAT1(Y701) levels in CD8(+) T cells were equivalent or higher in patients with RA compared with HC. Total STAT1 levels (phosphorylated + unphosphorylated) were lower in CD4(+) and CD8(+) T cells from patients with RA compared with HC. CONCLUSION: We report diminished IFN-γ-induced pSTAT1(Y701) levels in CD4(+) T cells in patients with RA, which were restored by TCR engagement. There were lower levels of total STAT1 in patients with RA compared with HC, but this likely does not explain diminished IFN-γ-induced pSTAT1(Y701) levels in CD4(+) T cells because activation in CD8(+) T cells was higher or equivalent to that seen in HC. The enhanced IFNGR expression in patients with RA reported previously may reflect a compensatory mechanism to overcome deficiency in IFN-γ responsiveness.
33570840 Isotemporal Substitution of Time Between Sleep and Physical Activity: Associations With Ca 2021 Mar OBJECTIVE: We aimed to determine relationships between objectively measured nightly sleep, sedentary behavior (SB), light physical activity (LPA), and moderate to vigorous physical activity (MVPA) with risk factors for cardiovascular disease (CVD) in patients with early rheumatoid arthritis (RA). Furthermore, we aimed to estimate consequences for these risk factors of theoretical displacements of 30 minutes per day in one behavior with the same duration of time in another. METHODS: This cross-sectional study included 78 patients with early RA. Nightly sleep, SB, LPA, and MVPA were assessed by a combined heart rate and accelerometer monitor. Associations with risk factors for CVD were analyzed using linear regression models and consequences of reallocating time between the behaviors by isotemporal substitution modeling. RESULTS: Median (Q1-Q3) nightly sleep duration was 4.6 (3.6-5.8) hours. Adjusted for monitor wear time, age, and sex, 30-minutes-longer sleep duration was associated with favorable changes in the values β (95% confidence interval [CI]) for waist circumference by -2.2 (-3.5, -0.9) cm, body mass index (BMI) by -0.9 (-1.4, -0.4) kg/m(2) , body fat by -1.5 (-2.3, -0.8)%, fat-free mass by 1.6 (0.8, 2.3)%, sleeping heart rate by -0.8 (-1.5, -0.1) beats per minute, and systolic blood pressure by -2.5 (-4.0, -1.0) mm Hg. Thirty-minute decreases in SB, LPA, or MVPA replaced with increased sleep was associated with decreased android fat and lower systolic blood pressure levels. Replacement of SB or LPA with MVPA yielded lower BMIs. CONCLUSION: Shorter sleep during the night is common among patients with early RA and is associated with adverse risk factors for CVD.
33932148 Testing the Effects of Disease-Modifying Antirheumatic Drugs on Vascular Inflammation in R 2021 Jun Individuals with rheumatoid arthritis (RA) are at increased risk for atherosclerotic cardiovascular disease (ASCVD) events relative to the general population, potentially mediated by atherosclerotic plaques that are more inflamed and rupture prone. We sought to address whether RA immunomodulators reduce vascular inflammation, thereby reducing ASCVD risk, and whether such reduction depends on the type of immunomodulator. The TARGET (Treatments Against RA and Effect on 18-Fluorodeoxyglucose [(18) F-FDG] Positron Emission Tomography [PET]/Computed Tomography [CT]) trial (NCT02374021) will enroll 150 patients with RA with active disease and an inadequate response to methotrexate. Participants will be randomized to add either a tumor necrosis factor (TNF) inhibitor (etanercept or adalimumab) or sulfasalazine and hydroxychloroquine to their background methotrexate. Participants will undergo full-body (18) F-FDG-labelled PET scanning at baseline and after 6 months. Efficacy and safety evaluations will occur every 6 weeks, with therapy modified in a treat-to-target approach. The primary outcome is the comparison of change in arterial inflammation in the wall of the aorta and carotid arteries between the randomized treatment groups, specifically, the change in the mean of the maximum target-to-background ratio of arterial (18) F-FDG uptake in the most diseased segment of either the aorta and carotid arteries. A secondary analysis will compare the effects of achieving low disease activity or remission with those of moderate to high disease activity on vascular inflammation. The TARGET trial will test, for the first time, whether RA treatments reduce arterial inflammation and whether such reduction differs according to treatment strategy with either TNF inhibitors or a combination of nonbiologic disease-modifying antirheumatic drugs.
33314148 Differential Binding of Sarilumab and Tocilizumab to IL-6Rα and Effects of Receptor Occup 2021 May We evaluated interleukin-6 (IL-6) receptor-α subunit (IL-6Rα) signaling inhibition with sarilumab and tocilizumab, the association between IL-6Rα receptor occupancy (RO) and C-reactive protein (CRP), and the potential clinical relevance of any differences. For this, we measured IL-6Rα binding and signaling inhibition with sarilumab and tocilizumab in vitro, simulated soluble IL-6Rα RO over time for approved sarilumab subcutaneous (SC) and tocilizumab intravenous (IV) and SC doses, and assessed associations between calculated RO and CRP reduction, 28-joint Disease Activity Score based on CRP, and 20%/50%/70% improvement in American College of Rheumatology responses from clinical data. Sarilumab binds IL-6Rα in vitro with 15- to 22-fold higher affinity than tocilizumab, and inhibits IL-6-mediated classical and trans signaling via membrane-bound and soluble IL-6Rα. Sarilumab 200 and 150 mg SC every 2 weeks achieved >90% RO after first and second doses, respectively, maintained throughout the treatment period. At steady-state trough, RO was greater with sarilumab 200 mg (98%) and 150 mg SC every 2 weeks (94%), and tocilizumab 162 mg SC weekly (>99%) and 8 mg/kg IV every 4 weeks (99%), vs tocilizumab 162 mg SC every 2 weeks (84%) and 4 mg/kg IV every 4 weeks (60%). Higher RO was associated with greater CRP reduction and 28-joint Disease Activity Score based on CRP reduction, and more sarilumab patients achieving 20%/50%/70% improvement in American College of Rheumatology responses. The greatest reduction in CRP levels was observed with sarilumab (both doses) and tocilizumab 8 mg/kg IV every 4 weeks (reductions proportionally smaller with 4 mg/kg IV every 4 weeks). Higher IL-6Rα binding affinity translated into higher RO with sarilumab vs tocilizumab 4 mg/kg every 4 weeks or 162 mg every 2 weeks; tocilizumab required the higher dose or increased frequency to maintain the same degree of RO and CRP reduction. Higher RO was associated with clinical parameter improvements.
34887848 Association Between a History of Nontyphoidal Salmonella and the Risk of Systemic Lupus Er 2021 OBJECTIVE: We investigated the correlation between nontyphoidal Salmonella (NTS) infection and systemic lupus erythematosus (SLE) risk. METHODS: This case-control study comprised 6,517 patients with newly diagnosed SLE between 2006 and 2013. Patients without SLE were randomly selected as the control group and were matched at a case-control ratio of 1:20 by age, sex, and index year. All study individuals were traced from the index date back to their NTS exposure, other relevant covariates, or to the beginning of year 2000. Conditional logistic regression analysis was used to analyze the risk of SLE with adjusted odds ratios (aORs) and 95% confidence intervals (CIs) between the NTS and control groups. RESULTS: The mean age was 37.8 years in the case and control groups. Females accounted for 85.5%. The aOR of having NTS infection were significantly increased in SLE relative to controls (aOR, 9.20; 95% CI, 4.51-18.78) in 1:20 sex-age matching analysis and (aOR, 7.47; 95% CI=2.08-26.82) in propensity score matching analysis. Subgroup analysis indicated that the SLE risk was high among those who dwelled in rural areas; had rheumatoid arthritis, multiple sclerosis, or Sjogren's syndrome; and developed intensive and severe NTS infection during admission. CONCLUSIONS: Exposure to NTS infection is associated with the development of subsequent SLE in Taiwanese individuals. Severe NTS infection and other autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, or Sjogren's syndrome also contributed to the risk of developing SLE.
34464467 The risk of chronic diseases and congenital malformations during childhood and adolescence 2021 Oct BACKGROUND: Women with autoimmune diseases, particularly inflammatory bowel disease (IBD), often need to continue immunomodulatory therapies during pregnancy. While the evidence of birth and short-term outcomes in children exposed in utero to these medicines is reassuring, long-term safety data are lacking. AIM: To assess any association between in utero exposure to thiopurines and diagnoses of chronic diseases (type 1 diabetes, coeliac disease, thyroid disease, rheumatoid arthritis, IBD and asthma) and congenital malformations during childhood and adolescence. METHODS: This nationwide cohort study was based on information using Danish registers and comprised all live-born children from 1995 to 2015 (N = 1 308 778). Children exposed in utero to thiopurines were followed for a median of 8.9 years (25%-75% percentiles 5.5-12.4 years); children not exposed were followed for 13.9 years (25%-75% percentiles 8.7-19.0 years). Analyses were adjusted for a number of confounders including the type of maternal underlying disease. RESULTS: A total of 1047 children had been exposed to thiopurines in utero; 96 developed a chronic disease and 126 were diagnosed with congenital malformations during follow-up. The adjusted hazard ratio for rheumatoid arthritis was 0.78 (95% CI 0.35-1.73); for IBD, it was 1.45 (95% CI 0.64-3.27); for asthma 0.94 (95% CI 0.73-1.21), and for congenital malformations, it was 0.95 (95% CI 0.78-1.15). For type 1 diabetes, coeliac disease, thyroid disease and ulcerative colitis, we had insufficient data to perform adjusted analysis. CONCLUSION: We found no increased risk of seven common chronic diseases or congenital malformations during childhood and adolescence after gestational exposure to thiopurines.
34731688 Suppression of experimental autoimmune encephalomyelitis by IgG Fc fragments bearing regRF 2021 Dec Previously we identified a rheumatoid factor, the production of which provides rats with resistance to experimental autoimmune diseases. It has been named regulatory rheumatoid factor (regRF). Immunization with conformers of IgG Fc fragments carrying epitopes specific to regRF reduces rat collagen-induced arthritis. The aim of this study was to determine whether IgG Fc fragments bearing regRF epitopes suppress experimental autoimmune encephalomyelitis, and to evaluate the potential of a strategy of stimulating production of regRF to treat multiple sclerosis. Two days after myelin basic protein injection, rats were immunized with Fc fragments exhibiting regRF epitopes, as well as with Fc fragments without those epitopes. The effect of Fc immunization on clinical signs of EAE and immunological parameters was evaluated. Stimulation of regRF production by IgG Fc fragments bearing regRF epitopes diminished EAE symptoms in rats, while immunization with Fc fragments without those epitopes worsened EAE. The improvement of EAE symptoms in rats treated with Fc fragments bearing regRF epitopes was associated with regRF production and with the relatively low number of blood CD4 T lymphocytes during disease development. In experiments involving immunizing intact rats and lymph node mononuclear cell cultures, Fc fragments bearing regRF epitopes decreased the CD4 T lymphocyte population indirectly, via regRF production. RegRF is a promising biotarget in MS, and Fc fragments bearing regRF epitopes are a potential therapeutic agent for MS.
33578802 The Subgingival Plaque Microbiome, Systemic Antibodies Against Bacteria and Citrullinated 2021 Feb 10 Periodontitis (PD) shows an association with rheumatoid arthritis (RA) and systemic inflammation. Periodontal pathogens, namely Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, are proposed to be capable of inducing citrullination of peptides in the gingiva, inducing the formation of anti-citrullinated protein antibodies (ACPAs) within susceptible hosts. Here, we sought to investigate whether periodontal treatment influenced systemic inflammation and antibody titres to P. gingivalis, A. actinomycetemcomitans, Prevotella intermedia and ACPA in 42 systemically health patients with periodontal disease. Subgingival plaque and serum samples were collected from study participants before (baseline) and 90 days after treatment to analyse the abundance of specific bacteria and evaluate anti-bacterial antibodies, C-reactive protein (CRP), tumour necrosis factor α (TNF-α), interleukin 6 (IL-6) and ACPA in serum. Following treatment, all patients showed reduced periodontal inflammation. Despite observing a weak positive correlation between CRP and IL-6 with periodontal inflammation at baseline, we observed no significant reductions in any indicators of systemic inflammation 90 days after treatment. In contrast, anti-P. gingivalis IgG significantly reduced post-treatment (p < 0.001, Wilcoxon signed rank test), although no changes were observed for other antibody titres. Patients who had detectable P. gingivalis in subgingival plaques had significantly higher anti-P. gingivalis IgG and ACPA titres, suggesting a potential association between P. gingivalis colonisation and systemic antibody titres.
34787296 Polyphenols for improvement of inflammation and symptoms in rheumatic diseases: systematic 2021 BACKGROUND: Rheumatic diseases (RDs) are a group of pathological conditions characterized by inflammation and functional disability. There is evidence suggesting that regular consumption of polyphenols has therapeutic effects capable of relieving RD symptoms. OBJECTIVE: To synthesize data from randomized controlled trials on administration of polyphenols and their effects on RD activity. DESIGN AND SETTING: Systematic review conducted at Universidade Federal de Ouro Preto, Minas Gerais, Brazil. METHODS: A systematic search was conducted in the databases PubMed (Medline), LILACS (BVS), IBECS (BVS), CUMED (BVS), BINACIS (BVS), EMBASE, Web of Science and Cochrane Library and in the grey literature. The present study followed a PRISMA-P checklist. RESULTS: In total, 646 articles were considered potentially eligible, of which 33 were then subjected to complete reading. Out of these, 17 randomized controlled trials articles were selected to form the final sample. Among these 17 articles, 64.71% assessed osteoarthritis (n = 11), 23.53% rheumatoid arthritis (n = 4), 5.88% rheumatoid arthritis and fibromyalgia (n = 1) and 5.88% osteoarthritis and rheumatoid (n = 1). Intake of polyphenol showed positive effects in most of the studies assessed (94.12%): it improved pain (64.70%) and inflammation (58.82%). CONCLUSION: Polyphenols are potential allies for treating RD activity. However, the range of polyphenol sources administered was a limitation of this review, as also was the lack of information about the methodological characteristics of the studies evaluated. Thus, further primary studies are needed in order to evaluate the effects of polyphenol consumption for reducing RD activity. SYSTEMATIC REVIEW REGISTER: PROSPERO - CRD42020145349.
34078428 A case report of a boy suffering from type 1 diabetes mellitus and familial Mediterranean 2021 Jun 2 BACKGROUND: Type 1 diabetes mellitus could be associated with other autoimmune diseases, such as autoimmune thyroid disease, celiac disease, but the association with Familial Mediterranean Fever is rare, we describe a case of a boy with type 1 Diabetes Mellitus associated with Familial Mediterranean Fever (FMF). CASE PRESENTATION: A 13 year old boy already suffering from Diabetes Mellitus type 1 since the age of 4 years, came to our attention because of periodic fever associated with abdominal pain, chest pain and arthralgia. The fever appeared every 15-30 days with peaks that reached 40 °C and lasted 24-48 h. Laboratory investigation, were normal between febrile episodes, but during the attacks revealed an increase in inflammatory markers. Suspecting Familial Mediterranean Fever molecular analysis of MEFV gene, was performed. The genetic analysis showed homozygous E148Q mutation. So Familial Mediterranean Fever was diagnosed and colchicine treatment was started with good response. CONCLUSION: Familial Mediterranean Fever could be associated with other autoimmune diseases such as Ankylosing Spondylitis, Rheumatoid Arthritis, Polyarteritis Nodosa, Behcet disease, Systemic Lupus, Henoch-Schönlein Purpura, and Hashimoto's Thyroiditis. Association of type 1 Diabetes Mellitus and Familial Mediterranean Fever has been newly reported in the medical literature, this is the third association of these two diseases described in the medical literature so far.
35128333 Radial tunnel syndrome in psoriatic enthesitis: Complication or coincidence? 2021 Dec Radial tunnel syndrome (RTS) is a rare condition resulting from posterior interosseous nerve (a branch of radial nerve) compression, within the radial tunnel. Lateral epicondylitis as a possible aetiology for RTS has been previously described. Here we report a 64-year-old female, with history of scalp psoriasis, who presented with pain over the lateral aspect of the left elbow and proximal forearm for one year, and decreased sensation over the lateral aspect of distal left forearm including the hand for 20 days. Examination revealed enthesitis at left lateral epicondyle, which was confirmed on magnetic resonance imaging. Touch and pain sensations were reduced over the left thumb, index finger, lateral aspect of the hand and distal forearm, and forearm pain was exaggerated with restricted extension of the wrist and third finger. Rheumatoid factor, anti-nuclear and anti-neutrophil cytoplasmic antibody were negative, and nerve conduction study were normal. A diagnosis of RTS as a possible complication of psoriatic enthesitis was suggested, and patient showed good response to non-steroidal anti-inflammatory drugs.
33823920 Stimulation of regulatory T cells with Lactococcus lactis expressing enterotoxigenic E. co 2021 Apr 6 BACKGROUND: Sjögren's syndrome (SjS), one of the most common autoimmune diseases, impacts millions of people annually. SjS results from autoimmune attack on exocrine (salivary and lacrimal) glands, and women are nine times more likely to be affected than men. To date, no vaccine or therapeutic exists to treat SjS, and patients must rely on lifelong therapies to alleviate symptoms. METHODS: Oral treatment with the adhesin from enterotoxigenic Escherichia coli colonization factor antigen I (CFA/I) fimbriae protects against several autoimmune diseases in an antigen (Ag)-independent manner. Lactococcus lactis, which was recently adapted to express CFA/I fimbriae (LL-CFA/I), effectively suppresses inflammation by the induction of infectious tolerance via Ag-specific regulatory T cells (Tregs), that produce IL-10 and TGF-β. To test the hypothesis that CFA/I fimbriae can offset the development of inflammatory T cells via Treg induction, oral treatments with LL-CFA/I were performed on the spontaneous, genetically defined model for SjS, C57BL/6.NOD-Aec1Aec2 mice to maintain salivary flow. RESULTS: Six-week (wk)-old C57BL/6.NOD-Aec1Aec2 mice were orally dosed with LL-CFA/I and treated every 3 wks; control groups were given L. lactis vector or PBS. LL-CFA/I-treated mice retained salivary flow up to 28 wks of age and showed significantly reduced incidence of inflammatory infiltration into the submandibular and lacrimal glands relative to PBS-treated mice. A significant increase in Foxp3(+) and IL-10- and TGF-β-producing Tregs was observed. Moreover, LL-CFA/I significantly reduced the expression of proinflammatory cytokines, IL-6, IL-17, GM-CSF, and IFN-γ. Adoptive transfer of CD4(+) T cells from LL-CFA/I-treated, not LL vector-treated mice, restored salivary flow in diseased SjS mice. CONCLUSION: These data demonstrate that oral LL-CFA/I reduce or halts SjS progression, and these studies will provide the basis for future testing in SjS patients.
34118806 1,25-dihydroxyvitamin D3 regulates t helper and b lymphocyte responses substantially in dr 2021 Oct 21 BACKGROUND/AIM: A correlation between vitamin D deficiency and primary Sjögren’s syndrome (pSS) has already been described. The limited data has been reported regarding the pathological relevance of vitamin D in primary Sjögren’s syndrome. In this study, the peripheral blood mononuclear cells were cocultured with 1,25-dihydroxyvitamin D3 to determine the modulatory effect of vitamin D3 on T and B lymphocyte phenotypes in pSS. MATERIALS AND METHODS: Venous blood samples were collected from 11 patients in the treatment phase and 9 drug-naive pSS patients. Peripheral blood mononuclear cells (PBMC) were isolated and separately cultured in the presence and absence of 1,25-dihydroxyvitamin D3 (10 mM) for 5 days of culture period. Lymphocyte proliferation was analyzed for CFSE signaling via flow cytometry. CD3+CD4+ cells were analyzed for intracellular IFN- and IL-17 expressions. CD19+IgD cells were analyzed for CD38 and CD27 expressions to evaluate naive and total memory B cell subsets. Culture supernatants were analyzed for the IFN-, IL-17, and IL-10 cytokine secretions via flow cytometry. RESULTS: 1,25-dihydroxyvitamin D3 significantly decreased Th lymphocyte proliferative responses in drug-naive (p < 0.005) and treated pSS patients (p < 0.05), and B lymphocyte proliferation in drug-naive pSS PBMC cultures (p < 0.01) compared to mononuclear cell cultures alone. 1,25-dihydroxyvitamin D3 significantly decreased IFN- and IL-17 secreting Th cells in both drug naive (p < 0.005 and p < 0.01, respectively) and treated subjects (p < 0.05 and p < 0.05, respectively) by increasing FoxP3 expressing CD4+CD25+ Treg cell frequency. Plasma B lymphocytes significantly reduced in the presence of 1,25-dihydroxyvitamin D3 in drug naive pSS (p < 0.001) and treated patients (p < 0.05) mononuclear cell cultures compared to PBMC cultures alone. Total memory B cell subsets significantly increased with 1,25-dihydroxyvitamin D3 in drug naive pSS when compared with PBMC cultures alone (p < 0.005). IFN- and IL-17 cytokine levels in culture supernatants significantly reduced (p < 0.05 and p < 0.01, respectively) in drug naive pSS patients’ PBMC cultures with 1,25-dihydroxyvitamin D3, and IL-10 levels significantly enhanced in both drug-naive (p < 0.01) and treated pSS patients’ PBMC cultures (p < 0.01) in the presence of 1,25-dihydroxyvitamin D3. CONCLUSION: In conclusion, 1,25-dihydroxyvitamin D3 regulated immune responses in both treated and drug-naive pSS patients, but have a more pronounced modulatory effect on mononuclear cell responses in drug-naive pSS patients.
33853628 Neuropsychological functioning and academic abilities in patients with juvenile idiopathic 2021 Apr 14 BACKGROUND: The involvement of the central nervous system is not rare in rheumatoid diseases. Even though children with juvenile idiopathic arthritis (JIA) may face academic difficulties until adulthood, very few studies have evaluated potential cognitive disorders in these patients. The present research aims to thoroughly investigate the cognitive and neuropsychological functioning of these patients. METHODS: We measured the cognitive profile of JIA patients via their neuropsychological profile, implicit memory and social cognition skills, and estimated their academic performance using reading and mathematics tests. We recruited 21 children with JIA aged 6 to 17 years-old (M = 11.01, SD = 3.30) and 21 healthy children matched in age, gender, academic level (same school class) and socioeconomic status. RESULTS: Our results showed that the cognitive profile and estimated academic ability of JIA patients are similar to those of their peers. These results support the hypothesis that children with JIA have the same cognitive predispositions to succeed at school as any other pupil. CONCLUSION: Comparing our results with the existing literature, we propose complementary hypotheses for further research. Longitudinal studies seem to be necessary to understand the psychosocial and cognitive processes involved in the development of children with JIA.
33464755 Unusual Case of Progressive Multifocal Leukoencephalopathy in a Patient With Sjögren Synd 2021 Jun 1 Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease caused by reactivation of John Cunningham virus affecting typically subcortical and periventricular white matter of immunocompromised hosts (human immunodeficiency virus infection, hematologic malignancies). Cerebral hemispheric white matter is most commonly affected by lytic infections, leading to progressive damage to oligodendrocytes in the central nervous system. Neuroimaging usually highlights scattered foci of white matter hypodensity not attributable to contrast enhancement or mass effect. In contrast, we present an unusual case of PML predominantly affecting cervical spinal cord and brainstem in an immunocompetent host. This is a rare subset of PML case that can occur in association with connective tissue disorders (Sjögren Syndrome in this case), systemic lupus erythematosus being the most common. Progressive multifocal leukoencephalopathy should be considered in the differential diagnosis of spinal cord or brainstem lesions, particularly in the patients with connective tissue disorders.