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ID PMID Title PublicationDate abstract
33603736 Single-Cell RNA Sequencing Reveals the Expansion of Cytotoxic CD4(+) T Lymphocytes and a L 2020 OBJECTIVE: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease, and its pathogenetic mechanism is far from being understood. In this study, we aimed to explore the cellular and molecular mechanisms that lead to pathogenesis of this disease. METHODS: We applied single-cell RNA sequencing (scRNA-seq) to 57,288 peripheral blood mononuclear cells (PBMCs) from five patients with pSS and five healthy controls. The immune cell subsets and susceptibility genes involved in the pathogenesis of pSS were analyzed. Flow cytometry was preformed to verify the result of scRNA-seq. RESULTS: We identified two subpopulations significantly expand in pSS patients. The one highly expressing cytotoxicity genes is named as CD4(+) CTLs cytotoxic T lymphocyte, and another highly expressing T cell receptor (TCR) variable gene is named as CD4(+) TRAV13-2+ T cell. Flow cytometry results showed the percentages of CD4(+) CTLs, which were profiled with CD4(+) and GZMB(+) staining; the total T cells of 10 patients with pSS were significantly higher than those of 10 healthy controls (P= 0.008). The expression level of IL-1β in macrophages, TCL1A in B cells, as well as interferon (IFN) response genes in most cell subsets was upregulated in the patients with pSS. Susceptibility genes including HLA-DRB5, CTLA4, and AQP3 were highly expressed in patients with pSS. CONCLUSIONS: Our data revealed disease-specific immune cell subsets and provided some potential new targets of pSS. Specific expansion of CD4(+) CTLs may be involved in the pathogenesis of pSS, which might give valuable insights for therapeutic interventions of pSS.
34912329 Transcriptomic and Single-Cell Analysis Reveals Regulatory Networks and Cellular Heterogen 2021 Sjögren's Syndrome (SS) is a chronic autoimmune disease of unknown etiology which primarily affects the salivary and lacrimal glands resulting in the loss of secretory function. Treatment options for SS have been hampered due to the lack of a better understanding of the underlying gene regulatory circuitry and the interplay between the myriad pathological cellular states that contribute to salivary gland dysfunction. To better elucidate the molecular nature of SS, we have performed RNA-sequencing analysis of the submandibular glands (SMG) of a well-established primary Sjögren's Syndrome (pSS) mouse model. Our comprehensive examination of global gene expression and comparative analyses with additional SS mouse models and human datasets, have identified a number of important pathways and regulatory networks that are relevant in SS pathobiology. To complement these studies, we have performed single-cell RNA sequencing to examine and identify the molecular and cellular heterogeneity of the diseased cell populations of the mouse SMG. Interrogation of the single-cell transcriptomes has shed light on the diversity of immune cells that are dysregulated in SS and importantly, revealed an activated state of the salivary gland epithelial cells that contribute to the global immune mediated responses. Overall, our broad studies have not only revealed key pathways, mediators and new biomarkers, but have also uncovered the complex nature of the cellular populations in the SMG that are likely to drive the progression of SS. These newly discovered insights into the underlying molecular mechanisms and cellular states of SS will better inform targeted therapeutic discoveries.
34925316 Perceptions of Rheumatologists on Diagnosis of Psoriatic Arthritis in China. 2021 OBJECTIVE: High prevalence of undiagnosed psoriatic arthritis (PsA) and prolonged diagnostic delay are key troubles in the appropriate management of PsA. To analyze the possible causes for this phenomenon, a web-based nationwide survey was conducted to investigate rheumatologists' perceptions on PsA diagnosis in China. METHODS: The electronic questionnaire consisting of 38 questions were designed by an expert panel and distributed with the online survey tool Sojump, which is a professional online survey platform. The completed questionnaires by real-name rheumatologists were collected. RESULTS: A total of 1594 valid questionnaires were included. More than half of Chinese rheumatologists reported it was challenging to make a diagnosis of PsA. The four major challenges were "Difficulties in identification of atypical or hidden psoriasis", "Absence of diagnostic biomarkers", "No active self-report of history or family history of psoriasis" and "Various musculoskeletal manifestations". In diagnosing PsA, minor participants had incorrect knowledge of inflammatory arthropathy (13.7%), acute phase reactant (23.8%), and rheumatoid factor (28.7%). There were no significant differences in the knowledge of PsA and practice habits in diagnosing PsA between modern western medicine (WM)- and traditional Chinese medicine (TCM)-rheumatologists. The part-time rheumatologists were not as good as full-time rheumatologists in diagnosing PsA. CONCLUSIONS: About three quarters of Chinese rheumatologists are familiar with the elements in PsA diagnosis and have good practice habits in diagnosing PsA. Four main challenges in making PsA diagnosis are revealed. There was no significant difference in the knowledge of PsA between WM- and TCM-rheumatologists.
33995991 Serum-derived exosomes containing NEAT1 promote the occurrence of rheumatoid arthritis thr 2021 BACKGROUND: Evidence has demonstrated that non-coding RNAs (ncRNAs) could be delivered efficiently to recipient cells using exosomes as a carrier. Additionally, long ncRNA nuclear enriched abundant transcript 1 (NEAT1) is emerging as a vital regulatory molecule in the progression of rheumatoid arthritis (RA). The aim of this study was to identify the NEAT1/miR-144-3p/Rho-associated protein kinase 2 (ROCK2) functional network regulating the WNT signaling pathway in RA. METHODS: In vivo, a collagen-induced arthritis (CIA) model was established to analyze the effects of blood exosomes on the incidence, clinical score, and bone degradation of RA. In vitro, the CD4(+)T cells were characterized by flow cytometry and the cell activities were analyzed in the presence of exosome treatment alone or in combination with altered expression of NEAT1, miR-144-3p or Rho-associated protein kinase 2 (ROCK2). The expression of NEAT1, miR-144-3p, ROCK2, and corresponding proteins in the WNT signaling pathway was detected by RT-qPCR and western blot techniques. The binding profile of NEAT1 to miR-144-3p was evaluated via a combination approach of luciferase activity assay, RNA immunoprecipitation, and RNA pull-down experiments. RESULTS: Blood exosomes extracted from RA patients increased the incidence of RA and bone destruction significantly. Overexpression of NEAT1 or ROCK2 promoted immune cell (CD4(+)T cells) proliferation, Th17 cell differentiation, and cell migration in response to stimulus, whereas knockout of the NEAT1 gene induced the expression of miR-144-3p in CD4(+)T cells. ROCK2 exogenous expression inhibited the expression of miR-144-3p, inducing activation of the WNT signaling pathway. CONCLUSION: A novel regulatory pathway NEAT1/miR-144-3p/ROCK2/WNT in RA was investigated as a potential target for RA therapy.
34835577 Construction of a Nano-Controlled Release Methotrexate Delivery System for the Treatment o 2021 Oct 23 A drug delivery system was specifically designed for the treatment of rheumatoid arthritis (RA) by local percutaneous administration and the nano-controlled release of methotrexate (MTX). The release behavior of MTX from the synthesized MTX-mSiO(2)@PDA system was investigated in vitro and in vivo. The obtained results show that after 48 h, twice as much MTX (cumulative amount) is released at pH 5.5 than at pH 7.4. This suggests that the MTX-mSiO(2)@PDA system exhibits a good pH sensitivity. In vitro local percutaneous administration experiments revealed that the cumulative amount of MTX transferred from MTX-mSiO(2)@PDA to pH 5.0 receptor fluid through the whole skin was approximately three times greater than the amount transferred to pH 7.4 receptor fluid after 24 h. Moreover, in vivo experiments conducted on a complete induced arthritis (CIA) model in DBA/1 mice demonstrated that the thickness of a mouse's toes decreases to nearly 65% of the initial level after 27 days of local percutaneous MTX-mSiO(2)@PDA administration. Compared to the mice directly injected with MTX, those administered with MTX-mSiO(2)@PDA by local percutaneous application exhibit much lower toe thickness deviation, which indicates that the latter group experiences a better cure stability. Overall, these results demonstrate that the local percutaneous administration of MTX delivery systems characterized by nano-controlled release may play an important role in RA therapy.
34850952 Undifferentiated arthritis; a changing population who did not benefit from enhanced DMARD- 2021 Nov 30 OBJECTIVES: International guidelines stress timely DMARD-initiation in early-arthritis, also when classification-criteria are not yet fulfilled. Consequently, undifferentiated arthritis (UA)-patients may be increasingly treated with DMARDs. Since UA is a diagnosis per exclusionem, the introduction of the 2010-classification-criteria presumably decreased the UA-population as former UA-patients became regarded as RA. The contemporary definition of UA has therefore become: not fulfilling the 1987- nor 2010-criteria. Importantly, placebo-controlled trials on DMARD-efficacy in contemporary UA are absent. We aimed to study whether enhanced treatment-strategies across 25-years improved outcomes in contemporary UA, whereby inclusion-period was an instrumental variable for DMARD-treatment. METHODS: UA was defined, retrospectively, as clinical arthritis (joint-swelling at physical-examination) neither fulfilling the 1987 nor 2010-RA-criteria, nor any other clinical diagnosis. In total, 1132 UA-patients, consecutively included in the Leiden-EAC between 1993-2019, were studied, divided into 5 inclusion-periods; 1993-1997, 1998-2005, 2006-2010, 2011-2014, 2015-2019. Frequency of DMARD-initiation was compared across the inclusion-periods, as were the following outcomes: DAS28CRP and disability (HAQ-DI) during follow-up, prevalence of DMARD-free-status within 10-years (DFS; spontaneous remission or sustained remission after DMARD-stop) and progression to RA (according 1987/2010-criteria). RESULTS: The contemporary UA-population is mainly autoantibody-negative, with median SJC = 2, TJC = 3 and HAQ = 0.6. These characteristics were similar across the inclusion-periods. DMARD-treatment increased from 17% (1993-1997) up-to 52% (2015-2019), methotrexate became more common. DAS28CRP during follow-up improved from 2011 onwards (-0.18,-0.25DAS-units/p< 0.05). Disability-scores during follow-up did not significantly improve. DFS-prevalence also remained similar: 58%, 57%, 61% (1993-1997/1998-2005/2006-2010; p= 0.77). Likewise, the percentages RA-development did not decrease (14%/21%/26%/18%/27%). CONCLUSION: Although intensified DMARD-treatment slightly improved disease-activity-scores, physical-functioning and long-term outcomes did not improve. This suggests overtreatment in the contemporary UA-population and underlines the importance to develop stratification-methods suitable for this population.
35125995 PD1/PD-L1 pathway in psoriasis and psoriatic arthritis: a review. 2021 Dec Programmed-death 1 (PD-1) is a co-receptor that inhibits the inflammatory response, and thus helps in maintenance of peripheral immunotolerance. Impairment in the PD-1/PD-L1 pathway is believed to play an important role in many immune-mediated diseases, including systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis and autoimmune hepatitis, and, as emphasized recently, in psoriasis and psoriatic arthritis. Biologic drugs targeting immune checkpoint regulators may be associated with new-onset psoriasis or exacerbations of pre-existing dermatosis. In this review we discuss the role of PD-1/PD-L1 pathway in psoriasis basing on data published to date.
34241971 The implication of interferon-γ-producing immunocompetent cells for evaluating disease ac 2021 Sep OBJECTIVE: To investigate the relationship between interferon-γ (IFN-γ), IFN-γ-producing immunocompetent cells, their related cytokines, and the clinical features in adult-onset Still's disease (AOSD). METHODS: Twenty-five patients with AOSD before initiating treatment (acute AOSD), 9 patients after remission (remission AOSD), and 12 healthy controls (HC) were included. Circulating IFN-γ-producing CD4+ and CD8+ cells, natural killer (NK) cells, and IFN-γ production in NK cells were evaluated by flow cytometry. Serum levels of IFN-γ, interleukin (IL)-6, IL-12, IL-15, and IL-18 were also measured. The obtained results were statistically analyzed with clinical findings. RESULTS: Serum levels of IFN-γ, IL-6, IL-12, IL-18, intracellular expression of IFN-γ in CD4+, CD8+, and NK cells were significantly higher in acute AOSD than in HC. The proportion of NK cells was significantly lower in acute AOSD than in HC. Serum levels of IFN-γ and IFN-γ expression in CD4+ cells were significantly correlated with serum ferritin levels. The proportion of NK cells had a significant inverse correlation with serum IFN-γ levels. A lower proportion of NK cells was significantly noted in patients refractory to initial immunosuppressive treatment. In remission AOSD, serum levels of IL-6, IL-12, and IL-18 were significantly higher than in HC. CONCLUSION: Increased serum levels of IFN-γ, increased expression of IFN-γ in CD4+ cells, and decreased NK cell proportion correlate with disease activity in AOSD. Moreover, a lower proportion of NK cells may be useful for predicting a refractory clinical course. Meanwhile, increased serum levels of IL-6, IL-12, and IL-18 may persist after clinical remission.
33780157 Association of F11R polymorphisms and gene expression with primary Sjögren's syndrome pat 2021 May AIMS: F11R gene encodes junctional adhesion molecule-A protein (JAM-A), which is expressed in various types of cells and is involved in leukocyte extravasation during inflammation. Sjögren's syndrome (SS) is a chronic systemic inflammatory disease that involves lymphocytes invasion of exocrine glands. F11R has been studied in autoimmune diseases, but any association between F11R and SS has not yet been investigated. Therefore, experiments were undertaken to examine the relationships among F11R gene polymorphism, messenger RNA (mRNA) expression and SS patients. METHODS: Three hundred and twenty-nine patients with SS, and 223 healthy controls were enrolled in their recruitment from the Kaohsiung Medical University Hospital. Genomic DNA was extracted from peripheral blood mononuclear cells and gene polymorphisms were genotyped by TaqMan real-time polymerase chain reaction (PCR). F11R mRNA expression was quantitated by quantitative real-time PCR with TaqMan Gene Expression Assay. RESULTS: Our study showed the genotype -688A/C (rs6695707) was not found in relation to SS patients. The odds ratio of -436A/G (rs12567886) genotype was notably associated with less susceptibility of SS in human leukocyte antigen (HLA)-DR2 negative and HLA-DR3 negative individuals. F11R mRNA expression was lower in SS patients than in the cells of healthy controls. CONCLUSION: The result indicated that G allele of -436A/G genotype has the potential protective effect against SS disease condition. F11R mRNA was expressed significantly lower in SS patients.
34518129 Immune disorders associated with juvenile recurrent chronic parotitis. 2021 Oct INTRODUCTION: Juvenile recurrent chronic parotitis (JRCP) is a rare disease of unknown cause. There is a growing interest in its autoimmune aetiology and its relationship with dysfunctions of cellular and humoral immunity, although there is no agreed protocol for complementary investigations for its study. A consecutive series of cases is presented where the immune alterations and associated autoimmune disorders are investigated, proposing a study algorithm. PATIENTS AND METHODS: A retrospective study was carried out on patients who had JRCP during the period from 2013 to 2016 and a follow-up of at least 2 years. After its clinical and ultrasound diagnosis, complementary examinations were systematically carried out to investigate infectious, immune, and autoimmune diseases. RESULTS: Of a total of 36 patients with inclusion criteria, 16 (44%) were found with some analytical alteration of a non-specific immunological nature (positive ANA, high IgG, low complement factor 4), or associated with a specific diagnosis, as occurred in 11 patients: Selective IgA deficiency (2), Sjögren's syndrome associated or not with systemic lupus erythematosus (3), coeliac disease associated or not with diabetes mellitus (4), Hashimoto's thyroiditis (1), and acquired immunodeficiency syndrome (1). CONCLUSION: Juvenile recurrent chronic parotitis can be considered a sentinel sign of other diseases of immunological/autoimmune aetiology for which the diagnosis, monitoring and early treatment can improve its prognosis. Viral infectious aetiology, with the exception of HIV, is not a priority in the study of recurrences.
33845818 The use of BokaFlo™ instrument to measure salivary flow. 2021 Apr 12 BACKGROUND: Dry mouth currently affects roughly 20% of the population and is a condition characterized by chronic hyposalivation and/or subjective reports of xerostomia. Low saliva flow can be indicative of other undiagnosed diseases, such as primary Sjogren's syndrome, and may contribute to difficulty chewing, increased caries susceptibility and infection. The passive drool test (PDT) is the primary method used to evaluate patients for hyposalivation but it is time-consuming and inconvenient. New methodology is needed to facilitate increased testing for hyposalivation in the dental clinic. The aim of this study was to evaluate an alternative method to measure salivary flow in dental offices. METHODS: In this study, we tested a new biomedical device, the BokaFlo™, to measure salivary flow in subjects in comparison to the current PDT standard. Participants completed an oral health questionnaire and saliva flow was evaluated by the PDT and the BokaFlo™ system. RESULTS: Saliva flow as measured by the BokaFlo™ positively correlated with the saliva flow measured by the PDT methodology (r = 0.22, p < 0.05). The device predicted low saliva flow in subjects with a sensitivity of 0.76 and specificity of 0.84 for subjects with hyposalivation, defined as a saliva flow rate of ≤ 0.1 ml/min. A significant negative correlation between the total oral health questionnaire score and the likelihood of participant exhibiting low salivary flow was observed (r = - 0.31, p < 0.006). CONCLUSION: The BokaFlo™ was effectively able to measure low saliva flow correlating with the PDT methodology and may provide more efficient testing of saliva flow in the dental office.
33385860 Understanding of cytokines and targeted therapy in macrophage activation syndrome. 2021 Feb Macrophage activation syndrome (MAS) is a potentially life-threatening complication of systemic autoinflammatory/autoimmune diseases, generally systemic juvenile idiopathic arthritis and adult-onset Still's disease. It is characterized by an excessive proliferation of macrophages and T lymphocytes. Recent research revealed that cytokine storm with elevated pro-inflammatory cytokines, including IFN-γ, IL-18, and IL-6, may be central to the pathogenesis of MAS. Though the mainstream of MAS treatment remains corticosteroids and cyclosporine, targeted therapies with anti-cytokine biologics are reported to be promising for controlling systemic inflammation in MAS.
34154345 The ratio of neutrophil to lymphocyte predicts interstitial lung disease and its prognosis 2021 Jun BACKGROUND: During the course of disease, some patients with primary Sjögren's syndrome (pSS) develop interstitial lung disease (ILD), which leads to a poor prognosis. There is currently a lack of methods to identify high-risk patients with ILD and predict the prognosis. The purpose of this study was to analyze the predictive value of the neutrophil to lymphocyte ratio (NLR) for the occurrence of ILD and its prognosis in patients with pSS. METHODS: According to the inclusion and exclusion criteria, patients with pSS admitted to our hospital from May 2009 to November 2020 were included. The patients were divided into either an ILD group or a non-interstitial pneumonia [non-ILD (NILD)] group. We compared the baseline data of the two groups of participants, and the participants were followed up (≥1 year) at clinic visits. Logistic multivariate regression analysis was used to analyze the risk factors related to ILD and prognosis in patients with pSS. RESULTS: A total of 217 patients with pSS were included, of which 71 (32.7%) participants were diagnosed with ILD (ILD group) at the time of pSS diagnosis, and 146 (67.3%) participants had no obvious ILD (NILD group). Based on follow-up results, logistic multivariate analysis revealed that NLR [relative risk (RR) =1.81, 95% confidence interval (CI): 1.15 to 4.73], age (RR =1.43, 95% CI: 1.06 to 3.66), non-regular treatment (RR =1.39, 95% CI: 1.03 to 3.38), ALB <35 g/L (RR =1.32, 95% CI: 1.05 to 3.17), and elevated CRP (RR =1.44, 95% CI: 1.10 to 4.53) were associated with the occurrence of ILD in participants with pSS during follow-up. Age (RR =1.28, 95% CI: 1.06 to 2.25), NLR (RR =1.43, 95% CI: 1.12 to 2.57), non-regular treatment (RR =1.51, 95% CI: 1.18 to 3.01), and ILD (RR =2.05, 95% CI: 1.36 to 4.72) were related to all-cause death during follow-up. CONCLUSIONS: The NLR is a risk factor for ILD in patients with pSS. The higher the NLR, the worse the prognosis; ILD significantly increases the risk of death in patients with pSS.
33323875 Ocular Surface Biomarkers. 2021 May 1 Sjögren syndrome (SS) is a chronic inflammatory autoimmune disease of the lacrimal and salivary glands. Salivary gland biopsy is still one of the most valuable and acceptable diagnostic tests for SS, which however, is an invasive test. Therefore, noninvasive diagnostic biomarkers with high specificity and sensitivity are required for the diagnosis and assessment of SS. Because ophthalmological testing constitutes to an important part for the diagnosis of SS. Tears harbor biomarkers with a high potential to be used for differential diagnosis and assessment of treatment in many systemic disorders, including SS. This review aims to summarize recent advances in the identification of tear biomarkers of SS, trying to identify reliable, sensitive, and specific biomarkers that can be used to guide treatment decisions.
32809145 Brainstem auditory evoked potentials in patients with primary Sjögren's syndrome without 2021 Mar OBJECTIVES: Primary Sjögren's syndrome (pSS) is an autoimmune, multisystem exocrinopathy characterized by dysfunction of the exocrine glands. Central nervous system (CNS) involvement is estimated to be present in 10-60% patients with pSS. The present study aimed to evaluate brainstem auditory evoked potentials (BAEP) in pSS patients without central nervous system involvement, and without otolaryngological abnormalities. METHOD: Thirty-six pSS patients (35 women, 1 man, mean age 48 years old) and 40 healthy volunteers were investigated. BAEP, brain imaging, laboratory parameters, and clinical neurological and otolaryngological examinations were performed. RESULTS: Abnormal BAEP were recorded in 16.7% patients. The mean wave BAEP I and V latency and mean wave III-V and I-V interpeak latencies were significantly longer in pSS patients than the controls. There were no statistically significant correlations between BAEP parameters and laboratory tests. None of the patients was found having the abnormalities on brain imaging. CONCLUSIONS: This study confirms that in pSS patients without clinical central nervous system impairment, auditory pathway disturbances could be found. Disorders of brain bioelectrical activity may be a consequence of ongoing autoimmune process. Key Points • BAEP abnormalities confirmed the clinically observed involvement of the central nervous system in patients with pSS. • Brain bioelectrical activity dysfunctions in pSS patients may be a consequence of ongoing inflammatory and/or immunological processes.
34751333 [Sjögren syndrome. Report of one case]. 2021 May Sjögren Syndrome (SS), a slowly Progressive disease that has unified, validated diagnostic criteria, with excellent evidence and performance in adults, but not in adolescents. We report a 17 year old teenager with a family history of SS in his sister and mother. He presented with fever and fatigue. He had an elevated C reactive protein, leukopenia, positive antinuclear and anti-Rho antibodies and rheumatoid factor. A scintigraphy showed a severe salivary gland dysfunction. The syndrome in this patient had a pediatric clinical behavior despite his proximity to adulthood.
34596023 Stepwise changes in the murine salivary gland immune response during virally-induced ectop 2021 Nov OBJECTIVES: Sjögren's syndrome (SS) is a chronic autoimmune disease characterised by lymphocytic infiltration into the salivary glands (SG) and, in a subset of patients, formation of ectopic lymphoid structures (ELS) in the glands. However, the mechanisms of how ELS form ectopically are not fully elucidated. Here we used a viral inducible murine model of ELS formation in the SG to elucidate the key immunological steps regulating the formation of ELS in the SG. METHODS: We have utilised an inducible murine model of sialadenitis whereby retrograde cannulation of the submandibular SG with a replication-deficient adenovirus 5 leads to the formation of ELS. Flow cytometry, immunofluorescence and gene expression was performed on the SGs at regular time points after cannulation to follow the organisation of ELS. RESULTS: Innate immune cells (neutrophils, eosinophils and monocytes) rapidly infiltrated the SG by 3 days post cannulation (dpc) whereby monocytes started to differentiate into resident macrophages. Myeloid dendritic cells accumulated inside leukocytic aggregates whereas macrophages were excluded from the developing ELS. Meanwhile, CD11b+ cells upregulated Il18, Cxcl13, Ltb, April and other lymphoid genes stimulating the influx of T cells by 12 days and B cells shortly after. Infiltration of T-follicular helper (Tfh) cells correlated with an increase in GL7+ germinal centre B cells, which peaked at 19 dpc. CONCLUSIONS: Immune cell infiltration in virally-infected murine SG follows a highly reproducible step-wise process whereby early innate immune cells reshape the SG myeloid compartment leading to upregulation of genes involved in the ectopic lymphoid neogenesis process. This in turns leads to T and B cell recruitment, differentiation and activation, culminating in the organization of ELS and localised germinal centres responses.
34596020 Differential Th follicular cell subsets in minor salivary glands of patients with primary 2021 Nov OBJECTIVES: T follicular helper cells (Tfh) have been recognised in minor salivary glands (MSG) of patients with primary Sjögren's syndrome (pSS). Nevertheless, if the Tfh1, Tfh2, Tfh17, Tfr phenotype is different when comparing pSS and associated SS in systemic lupus erythematosus (SLE) is unknown. METHODS: We included MSG biopsies from 8 pSS, 8 SLE/SS patients, 7 SLE patients, and 2 non-SS sicca patients. To determine the subpopulation of Tfh, a double-staining procedure for transcription factor B cell lymphoma 6 (Bcl-6)+/IL-17A+, Bcl6+/IL-4+, Bcl6+/IFN-γ+, and Bcl6+/Foxp3+ cells was performed. We estimated the mean percentage of positively staining cells in four fields per sample. RESULTS: Tfh1, Tfh2, and Tfh17 cells were highly expressed in pSS compared with the rest of the groups; conversely, in patients with SLE/SS predominated, the Tfh17 and in SLE patients the Tfh1 cells. Regulatory Tfh cells (Tfr) were similar in pSS and the rest of the patients. However, the lowest frequency was found in the SLE group. A positive correlation was observed between anti-Ro/SSA autoantibody and Tfh17 subset (r=0.726, p=0.0001); and with the (Tfh2+Tfh17)/Tfh1 ratio (r=0.844, p<0.0001) in the MSG of patients with pSS. CONCLUSIONS: We showed a differential Tfh profile in primary SS and SLE with associated SS. Whether this Tfh differential profile participates in the increased risk of lymphoproliferative disease in pSS compared with associated SS, or other outcomes, is yet to be determined in future studies.
34101572 Effect of low dose methotrexate as an add-on therapy in patients with palindromic rheumati 2021 Jul OBJECTIVE: Palindromic rheumatism (PR) is characterized by repetitive attacks of arthritis and/or periarthritis. There is inadequate data regarding the role of low dose methotrexate in patients with PR. The aim of this study was to determine the efficacy of low dose methotrexate add-on therapy in patients withPR with inadequate response to hydroxychloroquine (HCQ) monotherapy. METHODS: In this observational study, between August 2016 and July 2019, 15 patients with seropositive PR with inadequate response to HCQ (≥ 2attacks per month even after 6 months of therapy) were included. All patients were treated with oral low dose methotrexate in addition to HCQ. The responses to therapy were monitored 3 and 6 months after adding methotrexate. RESULTS: In our study, of the 15 patients with PR, two-third were female, with a mean age of 45.73±9.18 years. All were seropositive (Rheumatoid factor positive in eight patients; anti-cyclic citrullinated peptide [CCP] positive in 11 patients; both Rheumatoid factor and anti-CCP positive in four patients). The average number of attacks at baseline was 5.6±2.8, and the median duration of attacks was 2 years. All patients had significant response to add-on methotrexate therapy at follow-up after 3 and 6 months; none developed Rheumatoid arthritis (RA) after 2 years of follow-up. CONCLUSION: Low dose methotrexate is an effective add-on therapy in patients with PR having inadequate response to HCQ.
34583654 Rat bite fever due to Streptobacillus notomytis complicated by meningitis and spondylodisc 2021 Sep 28 BACKGROUND: Only three other cases of rat bite fever caused by Streptobacillus notomytis in humans have been reported since this species was identified in 2015. Data specific to the differences in clinical features and geographic distribution between S. notomytis infection and S. moniliformis infection are scarce. All previous cases of human S. notomytis infection were reported from Japan. This is the first case of S. notomytis infection reported from outside of Japan. CASE PRESENTATION: A 72-year-old Thai woman was admitted to Siriraj Hospital (Bangkok, Thailand)-Thailand's largest university-based national tertiary referral center-in August 2020 with fever, myalgia, and polyarthralgia for 3 days, and gradually decreased consciousness for the past 1 day. Physical examination and laboratory investigations revealed septic arthritis of both knee joints, meningitis, and hepatitis. She was initially misdiagnosed as rheumatoid arthritis in the elderly since the initial investigations were unable to detect a causative pathogen. However, S. notomytis infection was later confirmed by polymerase chain reaction amplification of a part of the 16S rRNA gene and sequencing from synovial fluid. Her clinical course was also complicated by spondylodiscitis and epidural abscess caused by S. notomytis, which was detected from tissue biopsy. Therefore, rat bite fever in this patient manifested as meningitis, septic polyarthritis, hepatitis, and spondylodiscitis. The patient was treated with intravenous ceftriaxone then switched to oral amoxicillin with complete recovery. CONCLUSIONS: The clinical manifestations of S. notomytis infection are similar to those demonstrated in S. moniliformis infection. This case also showed that arthritis caused by S. notomytis mimics rheumatoid arthritis, and that meningitis and spondylodiscitis are potential coexisting complications that can be found in S. notomytis infection.