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ID PMID Title PublicationDate abstract
33192583 Adipokines: New Potential Therapeutic Target for Obesity and Metabolic, Rheumatic, and Car 2020 Besides its role as an energy storage organ, adipose tissue can be viewed as a dynamic and complex endocrine organ, which produces and secretes several adipokines, including hormones, cytokines, extracellular matrix (ECM) proteins, and growth and vasoactive factors. A wide body of evidence showed that adipokines play a critical role in various biological and physiological functions, among which feeding modulation, inflammatory and immune function, glucose and lipid metabolism, and blood pressure control. The aim of this review is to summarize the effects of several adipokines, including leptin, diponectin, resistin, chemerin, lipocalin-2 (LCN2), vaspin, omentin, follistatin-like 1 (FSTL1), secreted protein acidic and rich in cysteine (SPARC), secreted frizzled-related protein 5 (SFRP5), C1q/TNF-related proteins (CTRPs), family with sequence similarity to 19 member A5 (FAM19A5), wingless-type inducible signaling pathway protein-1 (WISP1), progranulin (PGRN), nesfatin-1 (nesfatin), visfatin/PBEF/NAMPT, apelin, retinol binding protein 4 (RPB4), and plasminogen activator inhibitor-1 (PAI-1) in the regulation of insulin resistance and vascular function, as well as many aspects of inflammation and immunity and their potential role in managing obesity-associated diseases, including metabolic, osteoarticular, and cardiovascular diseases.
32598111 2020 Mar Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that primarily affects the joints of the body. Characterized by acute and chronic inflammation of the synovium, or soft tissue surrounding the joints, patients are subject to severe pain, stiffness, and fatigue, all of which can affect a patient’s ability to perform activities of daily living and overall health-related quality of life (HRQoL). Prolonged inflammation may lead to damage and destruction of the joints through erosion of the cartilage and bone and, consequently, disability and premature mortality. Other areas of the body may be affected as well, including the eyes, lungs, heart, or skin. It is estimated that about 1% of Canadians have the disease. Upadacitinib is a Janus kinase (JAK) inhibitor. JAK mediates the effects of cytokines and their production, thus JAK inhibitors may have more of a global effect on various cytokine production than do biologics, which tend to target specific cytokines. Upadacitinib is the third JAK inhibitor approved in Canada, the first being tofacitinib, followed by baricitinib, both of which were previously reviewed and issued recommendations by the CADTH Canadian Drug Expert Committee. The systematic review protocol for the current review was established before the granting of Notice of Compliance from Health Canada for upadacitinib. The objective is to perform a systematic review of the beneficial and harmful effects of upadacitinib 15 mg extended-release tablets for once daily administration for the treatment of moderate to severe RA in adult patients who have responded inadequately to, or who are intolerant to, one or more disease-modifying antirheumatic drugs (DMARDs). Upadacitinib may be used as monotherapy or in combination with methotrexate or other conventional synthetic DMARDs (csDMARDs).
32532571 Blepharospasm, dry eye and extractable nuclear antigen antibodies. 2020 Sep PURPOSE: To study whether there is an association between benign essential blepharospasm and Sjögren's syndrome by analyzing the presence of antibodies to extractable nuclear antigens in this population. METHODS: Seventy-two patients with benign essential blepharospasm (BEB) were included in this study. We excluded patients with hemifacial spasm or blepharospasm secondary to known corneal pathology. We recorded results of Schirmer I testing as well as levels of anti-SSA/Ro and anti-SSB/La antibodies. RESULTS: Our study included 72 patients (144 eyes), of which 62 (86.1%) were women. The mean age was 74.3±10.73 years. The mean Schirmer I test result was 3.14±4.00mm. Five women (8% of this female population) were found to have positive anti-SSA/Ro and anti-SSB/La antibodies. Their mean age was 65.66±13.24 years, while the mean age of the antibody-negative patients was 75.42±9.27 years. There was no statistically significant difference between the Schirmer I tests of the antibody positive and negative patients. CONCLUSION: This study demonstrates a possible association between Sjögren's syndrome and benign essential blepharospasm, justifying anti-SSA/Ro and anti-SSB/La testing in these patients.
32238618 Effectiveness of Profiling Serum IL-18 and Neopterin in Diagnosis of Adult-Onset Still's D 2020 Apr Adult-onset Still's Disease (AOSD) is a systemic inflammatory disorder characterized by high fever, skin rashes, and joint pains, and is extremely rare in patients over 80 years of age. An 88-year-old woman was admitted with high fever lasting for > 2 weeks and arthritis of the right knee and bilateral wrists. Further examination revealed that the patient fulfilled the Yamaguchi criteria, the most sensitive and extensively used classification criteria for AOSD. After ruling out other causes and considering a greatly raised serum interleukin-18 (IL-18) level, the patient was diagnosed with AOSD. Before prednisolone therapy, active tuberculosis was excluded using chest computed tomography (CT) and an interferon-gamma release assay (IGRA). After starting the treatment, serum levels of IL-18 and acute-phase reactants were decreased gradually. However, during prednisolone tapering, fever relapsed along with increasing serum acute phase reactant levels. Her serum IL-18 level was decreased but remained at a high level, and the neopterin level was further increased. These findings suggested the onset of another disease, but not AOSD recurrence. A chest CT scan revealed new lung infiltrates. Despite the initial negative IGRA result, cultures and polymerase chain reaction tests of bronchoalveolar lavage and sputum were positive for Mycobacterium tuberculosis. She was placed on a 9-month course of anti-tuberculosis therapy and continued prednisolone tapering. She showed steady improvement and her cytokine profile showed a decrease in the IL-18 and neopterin levels. In conclusion, cytokine profiling is useful in making the diagnosis of AOSD and subsequent pulmonary tuberculosis developed during steroid therapy.
33333235 Targeted therapies in interstitial lung disease secondary to systemic autoimmune rheumatic 2021 Feb Autoimmune rheumatic diseases (ARD) are characterized by systemic manifestations and multiple organ involvement, including the lung. Interstitial Lung Disease (ILD) is a cardinal manifestation of lung involvement in patients with ARD and is associated with significant morbidity and mortality. Corticosteroids and immunosuppressive drugs are used as first -line treatment. Targeted therapies, such as biological disease modifying antirheumatic drugs (DMARDS) and anti- fibrotic agents are new treatment options. In this review we discuss the role of targeted therapies in patients with ILD secondary to ARD.
33196001 Practical Issues in Managing Systemic Inflammatory Disorders During the COVID-19 Pandemic. 2020 Sep The global coronavirus disease 2019 (COVID-19) situation threatens not only the health of populations, but also the coherence and function of health care systems. Patients with systemic inflammatory disorders feel the overwhelming strain of COVID-19, since their disease, administered treatments, and associated comorbidities may all contribute to increased vulnerability to infection. At the same time, monitoring the activity status of rheumatic diseases and adjusting the treatments where appropriate, are important for preventing flares and other complications, which could pose additional health risks. Considering the urgent need to maintain physical distancing and self-quarantine as much as possible, we herein discuss the challenges and possible solutions pertaining to the assessment and monitoring of patients with systemic inflammatory diseases. We also discuss issues related to the prescription and supply of anti-rheumatic drugs, as well as opportunities provided by the use of technological and wireless tools. From an optimistic viewpoint, the end of this pandemic may leave us with an important legacy in utilising and implementing e-health solutions that may both improve the clinical care standards for patients with systemic inflammatory diseases and also reduce the burden placed on healthcare systems.
32083090 New Developments in Transcriptomic Analysis of Synovial Tissue. 2020 Transcriptomic technologies are constantly changing and improving, resulting in an ever increasing understanding of gene expression in health and disease. These technologies have been used to investigate the pathological changes occurring in the joints of rheumatoid arthritis patients, leading to discoveries of disease mechanisms, and novel potential therapeutic targets. Microarrays were initially used on both whole tissue and cell subsets to investigate research questions, with bulk RNA sequencing allowing for further elaboration of these findings. A key example is the classification of pathotypes in rheumatoid arthritis using RNA sequencing that had previously been discovered using microarray and histology. Single-cell sequencing has now delivered a step change in understanding of the diversity and function of subpopulations of cells, in particular synovial fibroblasts. Future technologies, such as high resolution spatial transcriptomics, will enable step changes integrating single cell transcriptomic and geographic data to provide an integrated understanding of synovial pathology.
31645179 An update on investigations of autoimmune diseases affecting orofacial region. 2020 Autoimmune diseases are better diagnosed currently with advances in cellular immunology, molecular biology, and genetics. Clinical diagnosis of systemic and organ specific autoimmune diseases is a challenging task for the Oral physicians and the development of chairside investigation methods has not only saved the time but also cost factor. To understand patient's immune status, the clinical chair side diagnostic aids along with laboratory testing methods are necessary. Laboratory investigations have great importance in detecting, confirming and analyzing the severity, and predicting the prognosis of the autoimmune disease. This article aims to list out the diagnostic methods to diagnose autoimmune conditions and focuses on various diagnostic methods to effectively evaluate autoimmune disease of orofacial region.
32253547 Angiopoietin-like protein 2 as a novel marker for patients with primary Sjogren's syndrome 2020 Aug Angiopoietin-like protein 2 (Angptl2) plays a key role in chronic inflammation and tissue remodeling. We evaluated whether serum Angptl2 is associated with interstitial lung disease (ILD) in primary Sjogren's syndrome (pSS) patients. A total of 158 consecutive pSS patients and 25 normal healthy controls, which completed lung HRCT, were enrolled in our research. The levels of serum Angptl2 and TGF-β1 were measured by enzyme-linked immunosorbent assay. We investigated the correlation between the activity indexes of pSS-ILD patients and the serum Angptl2 levels. There were 71 of 158 (44.94%) patients interpreted pSS-ILD by radiologists at the initial presentation. The median interquartile range for serum Angptl2 was 16.55 ng/mL (range 10.82-41.07) in pSS patients, compared with 6.05 ng/mL (range 3.53-9.91) in normal healthy controls (P < 0.001). Importantly, differences between Angptl2 levels in pSS-ILD patients and pSS-N-ILD patients were also statistically significant [29.80 ng/mL (range 15.42-54.40), 14.75 ng/mL (range 9.85-40.48), P < 0.001]. A logistic regression analysis suggested that anti-Ro52, serum Angptl2 and DLCO were associated with pSS patients with interstitial lung disease, with aORs and 95% CIs of 2.06 (1.14-7.65), 4.13 (1.25-15.89) and 9.51 (2.10-37.74), respectively. Moreover, anti-Ro52 (r(s) = 0.48, P = 0.016) and TGF-β1 (r(s) = 0.64, P = 0.003) were significantly correlated with the serum Angptl2 in pSS-ILD patients. And, in pulmonary function tests, the serum Angptl2 was significantly correlated with DLCO (r(s) = - 0.40, P = 0.009) and FVC (r(s) = -0.37, P = 0.020). Serum Angptl2 may display a peculiar role in the pathogenesis of pSS-ILD and might be a potential biomarker.
31899698 Bacterial Septic Arthritis of the Adult Native Knee Joint: A Review. 2020 Jan » Acute bacterial septic arthritis of the knee is an orthopaedic emergency and, if left untreated, can result in substantial joint degradation. » Important risk factors for development of septic arthritis include age of >60 years, recent bacteremia, diabetes, cancer, cirrhosis, renal disease, drug or alcohol abuse, a history of corticosteroid injection, a recent injury or surgical procedure, a prosthetic joint, and a history of rheumatoid arthritis. » The diagnosis is primarily based on history and clinical presentation of a red, warm, swollen, and painful joint with limited range of motion. Laboratory values and inflammatory markers from serum and joint fluid may serve as adjuncts when there is clinical suspicion of septic arthritis. » The initial and general antibiotic regimen should cover methicillin-resistant Staphylococcus aureus and gram-negative and gram-positive organisms. The antibiotic regimen should be specified following the culture results of the infected joint. » Operative management involves either arthrotomy or arthroscopy of the knee with thorough irrigation and debridement of all infected tissue. The Gächter classification is useful in establishing a prognosis or in determining the need for an extensive debridement.
33025890 When B cells break bad: development of pathogenic B cells in Sjögren's syndrome. 2020 Jul Primary Sjögren's syndrome (pSS) is often considered a B cell-mediated disease, yet the precise role of B cells in the pathogenesis is not fully understood. This is exemplified by the failure of multiple clinical trials directed at B cell depletion or inhibition. To date, most prognostic markers for severe disease outcomes are autoantibodies, but the underlying mechanisms by which B cells drive diverse disease presentations in pSS likely extend beyond autoantibody production. Here we outline an expanded role of B cells in disease pathogenesis drawing on examples from animal models of SS, and from other autoimmune diseases that share similar clinical or immunological abnormalities. We focus on recent findings from the detailed analysis of pathogenic B cells in patients with pSS to propose strategies for patient stratification to improve clinical trial outcomes. We conclude that an integrated cellular, molecular and genetic analysis of patients with pSS will reveal the underlying pathogenic mechanisms and guide precision medicine.
32576236 Elevated expression of BAFF receptor, BR3, on monocytes correlates with B cell activation 2020 Jun 23 BACKGROUND: We reported that the production of BAFF (B cell-activating factor) and IL-6, both of which are involved in survival and differentiation of B cells, is dysregulated in monocytes of patients with primary Sjögren's syndrome (pSS). In this study, we investigate the relationship between possible aberrations of pSS monocytes and clinical features of pSS patients and the contribution of monocytes to B cell activation, a mechanism involved in the pathogenesis of pSS. METHODS: Expression of BAFF-receptor (BR3) on peripheral monocytes from patients with pSS (n = 67) and healthy controls (HC: n = 37) was analyzed by FACS. Peripheral monocytes were stimulated with BAFF, and IL-6 production by the cells was measured by ELISA. Peripheral B cells were cultured with BAFF-stimulated monocytes in the presence or absence of anti-IL-6 receptor antibody, and IgG production by the cells was measured by ELISA. Patients' serological data were collected from their clinical records. Patients' disease activity was quantified based on their EULAR Sjögren's syndrome disease activity index (ESSDAI) scores. RESULTS: The proportion of peripheral BR3-positive monocytes (BR3(+)/CD14(+)) was significantly increased in pSS patients compared to HC. Moreover, IL-6 production by BAFF-stimulated monocytes was remarkably higher than HC and was significantly correlated with BR3(+)/CD14(+) ratios of patients. In addition, BR3 expression on pSS monocytes was elevated in anti-Ro/SSA and/or anti-La/SSB positive compared to negative patients. Remarkably, BR3 expression on peripheral monocytes was positively and significantly correlated with patients' serum IgG and IgM levels and ESSDAI scores. Moreover, the amount of IgG produced by B cells was markedly higher in pSS patients compared to HC when the cells were co-cultured with BAFF-stimulated autologous monocytes in vitro. Notably, addition of anti-IL-6 receptor antibody into the co-culture system led to inhibition of IgG production by B cells. CONCLUSIONS: Our data suggest that elevated BR3 expression in monocytes is associated with clinical features in pSS patients and that enhanced production of IL-6 by BAFF-stimulated monocytes plays a part in the overproduction of IgG by B cells in pSS. These results suggest that BAFF signaling pathways through BR3 in monocytes are possible therapeutic targets for pSS.
33187286 Impact of Single-Nucleotide Polymorphisms of CTLA-4, CD80 and CD86 on the Effectiveness of 2020 Nov 11 Abatacept (ABA) is used as a first-line treatment in patients diagnosed with moderate and severe rheumatoid arthritis (RA). The interindividual response to ABA therapy is very variable in these patients. The objective of our study was therefore to investigate the role of polymorphisms of the CTLA-4, CD80 and CD86 genes, as well as that of clinical factors of the disease, in the response to ABA in patients with RA. A retrospective cohort study was carried out in 109 patients receiving treatment with ABA and diagnosed with RA. The genetic variables were analyzed using real-time PCR with TaqMan(®) probes. The patients were classified according to the European League Against Rheumatism (EULAR) criteria at 6 and 12 months from start of treatment. The independent variables associated with higher EULAR response were lower duration of previous biologic disease-modifying anti-rheumatic drugs and lower baseline values of the disease activity score 28 after 6 months of ABA treatment; and lower baseline patient's visual analogue scale (PVAS) after 12 months. In addition, a significant association was found between duration of ABA treatment, non-administration of concomitant glucocorticoids and lower baseline values of the number of inflamed joints and erythrocyte sedimentation rate clinical variables, with remission of the disease after 6 months' treatment with ABA. Finally, remission of the disease after 12 months' treatment with ABA was associated with earlier age at start of ABA therapy and lower number of previous biologic therapies (BTs). The CTLA-4rs5742909-T allele and the CTLA-4rs231775-G allele were found to be associated with satisfactory EULAR response and low disease activity (LDA) after 12 months' treatment with ABA (CTLA-4rs5742909 T vs. CC; OR = 5.88; CI(95%) = 1.48-23.29 and OR = 4.75; CI(95%) = 1.35-17.94, respectively, and CTLA-4rs231775 G vs. AA, OR = 3.48; CI(95%) = 1.20-10.09 and OR = 4.68; CI(95%) = 1.49-17.94, respectively). In conclusion, patients with RA treated with ABA showed better EULAR response and LDA rate when they had the CTLA-4 rs5742909-T or CTLA-4 rs231775-G polymorphisms; furthermore, this remission rate increased in patients that began ABA treatment earlier, those with a lower number of previous BTs and those with a lower PVAS value.
32272752 Expansion of Rare and Harmful Lineages is Associated with Established Rheumatoid Arthritis 2020 Apr 7 OBJECTIVES: To characterize the gut microbiota profile in rheumatoid arthritis (RA) patients and investigate its association with certain characteristics of RA. PATIENTS AND METHODS: A nested case-control cohort of 40 patients with RA and 40 sex-age matched controls was studied. Subjects with diabetes, with any other inflammatory disease, practicing extreme diets, taking antibiotics, probiotics or under any new treatment for at least three months prior to sampling were excluded. The microbiota composition was determined by 16S rRNA pyrosequencing and bioinformatics analysis by Quantitative Insights Into Microbial Ecology (QIIME). Other variables included clinical-laboratory variables and average Disease Activity Score 28 points during the follow-up period. Multiple linear regression models were constructed to investigate the possible risk factors for the microbiota. RESULTS: β-diversity data showed that patients tend to differ from healthy subjects according to their microbiota (p = 0.07). The analysis showed an increase in Collinsella aerofaciens, Sedimentibacter and Enterococcus genera in patients compared to controls, as well as a decrease in Dorea formicigenerans. Likewise, an increase in the activity of arginine deiminase was observed, which was found in approximately 90% of the RA genes of the genus Collinsela. The sequence number of Collinsella aerofaciens was independently associated with age (B (95%CI), -0.347 (-21.6, -2.1)), high ACPA (0.323 (27.4-390.0)) and smoking (0.300 (8.8-256.4)) in RA patients. In addition, we observed decreases in Sarcina, 02d06 and Porphyromonas bacterial lineages. CONCLUSION: Patients with RA present dysbiosis, resulting from an abundance of certain bacterial lineages and a decrease in others. These alterations could influence the maintenance of autoimmunity to this disease.
32103892 Dynamic Contrast-Enhanced MRI Confirms Rapid And Sustained Improvement Of Rheumatoid Arthr 2020 OBJECTIVE: This open-label study evaluated the effects of combined tocilizumab (TCZ) and disease-modifying antirheumatic drugs (DMARDs) on magnetic resonance imaging (MRI) changes in synovial membrane enhancement, bone marrow edema (BME), and erosions in the wrist and hand joints of rheumatoid arthritis (RA) patients inadequately responding to DMARDs alone. METHODS: The efficacy of intravenous TCZ 8 mg/kg administered every four weeks for 48 weeks was evaluated on six occasions. The primary endpoints were the changes in the extent and degree of wrist synovitis as measured using the RA MRI Score (RAMRIS) and dynamic, gadolinium-enhanced 0.2T MRI (DCE-MRI). A number of different parameters of DCE-MRI were evaluated. RESULTS: Fifty-eight patients were treated, eight of whom (13.8%) discontinued the study prematurely. The mean RAMRIS significantly decreased after two weeks and the decrease was maintained for up to 48 weeks. By week 4, the mean RAMRIS synovitis score had significantly decreased from baseline (-0.804±1.575; p=0.018), but not the mean early enhancement (REE) or relative enhancement (RE). However, there were significant decreases in RE at week 24, in REE and N(total) (total number of enhancing voxels)*IRE (initial rate of enhancement) at weeks 12, 24 and 48, and in N(total)*ME (maximal enhancement) at weeks 24 and 48. Mean BME decreased from baseline to week 48, and bone erosions did not progress. The patients' clinical parameters significantly improved from baseline until week 48. CONCLUSION: TCZ in combination with DMARDs improved wrist synovitis, BME and clinical parameters, without any progression in bone erosions. The RAMRIS for synovitis rapidly improved from as early as two weeks after the first TCZ infusion. (Funded by F. Hoffmann-La Roche; ACTRACE EudraCT No. 2009 012185-32).
33312533 Major dietary patterns and food groups in relation to rheumatoid arthritis in newly diagno 2020 Dec BACKGROUND: Evidence suggests that dietary patterns might act as environmental triggers in the development of chronic disorders such as rheumatoid arthritis (RA). However, data regarding the relationship between food patterns and RA are still limited and conflicting. In the current study, the authors aim to evaluate a link between major dietary patterns and RA in new case patients. METHODS: This study was conducted in a case-control manner on 50 patients with newly diagnosed RA and 100 healthy individuals living in Mashhad, Iran. The individuals' dietary intake was assessed using a validated food frequency questionnaire (FFQ). The major dietary patterns were identified using factor analysis based on data from FFQ. Multivariable-adjusted logistic regression models were used to measure the associations between patterns and RA. RESULTS: Three major dietary patterns were identified. High-level adherence to Western pattern had a positive association with RA (multivariable-adjusted OR tertile 3 vs. 1:1.95; 95% CI: 1.09-3.92; p-trend: .046), while the healthy pattern was inversely related to RA (multivariable-adjusted OR tertile 3 vs. 1:0.12; 95% CI: 0.03-0.44; p-trend: .001). No significant association was observed between the traditional pattern and RA. CONCLUSIONS: Our findings revealed that people with dietary behaviors close to the Western dietary pattern are more likely to develop the disease. However, adhering to healthy and well-balanced dietary patterns rich in whole grains, low-fat dairies, white meats, eggs, fruits, vegetables, tea, and vegetable oils was found to be inversely correlated with the risk of RA.
31963908 Safety of Abatacept in Italian Patients with Rheumatoid Arthritis and Interstitial Lung Di 2020 Jan 19 BACKGROUND: Treatment of rheumatoid arthritis (RA)-related interstitial lung disease (ILD) is challenging, and many conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs) have been associated with ILD development or progression. The aim of this multicentric retrospective study was to analyze the evolution of ILD in Italian RA-ILD patients treated with abatacept (ABA). METHODS: All RA-ILD patients treated with ABA for at least six months were retrospectively evaluated. Serology, previous and concurrent therapies, chest high-resolution computer tomography (HRCT), forced vital capacity (FVC), and lung diffusion of carbon monoxide (CO, DLCO) were collected. RESULTS: Forty-four patients were included; HRCT, FVC, and DLCO were analyzed at baseline, at one year, and at the end of follow-up. A remission or a low disease activity of RA was reached in 41/44 patients. Overall, FVC and DLCO remained stable or increased in 86.1% and 91.7% of patients, respectively, while HRCT was stable or improved in 81.4% of them. Previous and concurrent treatments, in particular, methotrexate, serology, age, sex, joint and lung disease duration were not associated with the outcome at univariate analysis. CONCLUSION: The management of RA-ILD patients remains a critical unmet medical need. Waiting for prospective controlled studies, ABA has shown a good safety profile in our cohort of Italian RA-ILD patients.
33047725 [Association of Semaphorin 3A with thrombocytopenia in systemic lupus erythematosus]. 2020 Oct 18 OBJECTIVE: To measure the level of serum Semaphorin 3A (Sema3A) and to analyze the relationship between serum Sema3A and systemic lupus erythematosus (SLE) with thrombocytopenia. METHODS: The concentration of serum Sema3A was detected by enzyme-linked immuno sorbent assay (ELISA) in 170 SLE patients, 50 Sjögren's syndrome (SS) patients, 19 hypersplenism (HS) patients and 150 healthy controls (HC). Based on the presence of thrombocytopenia and whether the thrombocytopenia was in remission, the SLE patients were divided into three groups: SLE with thrombocytopenia (41 cases), SLE with thrombocytopenia remission (28 cases), and SLE without thrombocytopenia (101 cases). According to whether there was thrombocytopenia, the SS patients were divided into SS with thrombocytopenia (18 cases) and SS without thrombocytopenia (32 cases). The 28 SLE patients who underwent bone marrow aspiration biopsy were divided into two groups from the aspect of whether the bone marrow hyperplasia was normal (19 cases) or low (9 cases), as well as from the aspect of whether the maturity disturbance of megakaryocyte was positive (8 cases) or negative (20 cases). The serum Sema3A levels in SLE, SS, HS with HC were compared, meanwhile, the correlation between serum Sema3A level and platelet (PLT) in the patients with different diseases analyzed. RESULTS: (1) Serum Sema3A levels in SLE were significantly lower than in HC [(3.84±2.76) μg/L vs. (6.96±2.62) μg/L, P < 0.001], serum Sema3A levels in SS were also obviously lower than in HC [(4.35±3.57) μg/L vs. (6.96±2.62) μg/L, P < 0.001], and in HS it was lower than HC at a certain extant [(5.67±2.26) μg/L vs. (6.96±2.62) μg/L, P=0.041]. (2) Serum Sema3A levels in SLE were slightly lower than in SS, but there was no significant difference [(3.84±2.76) μg/L vs. (4.35±3.57) μg/L, P=0.282]. However, when compared with HS, serum Sema3A levels in SLE were significantly lower [(3.84±2.76) μg/L vs. (5.67±2.26) μg/L, P=0.006]. (3) Serum Sema3A concentration in SLE with thrombocytopenia was significantly lower than in SLE with thrombocytopenia remission [(1.28±1.06) μg/L vs. (3.83±2.65) μg/L, P < 0.001], and in SLE patients without thrombocytopenia [(1.28±1.06) μg/L vs. (4.87±2.60) μg/L, P < 0.001]. There was no significant difference between SLE with thrombocytopenia remission and SLE without thrombocytopenia [(3.83±2.65) μg/L vs. (4.87±2.600 μg/L, P=0.123]. Serum Sema3A concentration in SLE with thrombocytopenia was slightly lower than in SS with thrombocytopenia, but there was no significant difference [(1.28±1.06) μg/L vs. (1.68±1.11) μg/L, P=0.189]. (4) Strong positive correlations were found between serum Sema3A and PLT in SLE (r=0.600, P < 0.001). Positive correlations were also found between serum Sema3A and PLT in SS (r=0.573, P < 0.001). However, there was no such correlation showed in HS patients (P=0.393). (5) There was no significant difference of serum Sema3A concentration in SLE whether the bone marrow hyperplasia was normal or low. And the same situation appeared in the patients whether the maturity disturbance of megakaryocyte was positive or negative (P>0.05). CONCLUSION: Serum Sema3A was significantly reduced in SLE patients, and it was highly correlated with the blood damage. Similar conclusions could be drawn in patients with SS. The serum level of Sema3A was generally decreasing in desmosis which merged thrombocytopenia, and was obviously positive correlated with platelet counts.
32242817 Aberrant distribution of CD3+CD56+ NKT-like cells in patients with primary Sjögren's synd 2021 Jan OBJECTIVES: To elucidate the potential role of CD3+CD56+ NKT-like cells in the pathogenesis of primary Sjögren's syndrome (pSS). METHODS: We enrolled pSS patients and healthy controls and examined the peripheral population, the surface chemokine receptors and the proinflammatory cytokine production of NKT-like cells by flow cytometry. The infiltration of NKT-like cells in the labial salivary gland (LSG) was examined by immunofluorescence. Serum and tissue levels of CX3CL1 were detected by Cytometric Bead Array and immunohistochemistry, respectively. The chemotaxis of NKT-like cells was examined by transwell migration assay. RESULTS: Peripheral NKT-like cells from pSS patients were significantly lower than those from HC (3.09±2.35% vs. 5.37±4.06%, p=0.0002), which was negatively correlated with European League Against Rheumatism Sjögren's Syndrome Disease Activity index. NKT-like cells infiltrated into the LSG of pSS patients. Serum and LSG epithelial CX3CL1 levels were higher in pSS patients than those in HC, which promoted the chemotaxis of the NKT-like cells. NKT-like cells from pSS patients expressed a higher level of CD69, and secreted high level of TNF-α and IFN-γ, which was promoted by CX3CL1 in vitro. CONCLUSIONS: NKT-like cells decreased in peripheral and infiltrated into the LSG of the pSS patients, which could be driven by CX3CL1-CX3CR1 axis. NKT-like cells might be implicated in the pathogenesis of pSS.
33356170 Intralacrimal Sustained Delivery of Rapamycin Shows Therapeutic Effects without Systemic T 2021 Mar 8 Sjögren's syndrome (SS) is an autoimmune disease associated with severe exocrinopathy, which is characterized by profound lymphocytic infiltration (dacryoadenitis) and loss of function of the tear-producing lacrimal glands (LGs). Systemic administration of Rapamycin (Rapa) significantly reduces LG inflammation in the male Nonobese Diabetic (NOD) model of SS-associated autoimmune dacryoadenitis. However, the systemic toxicity of this potent immunosuppressant limits its application. As an alternative, this paper reports an intra-LG delivery method using a depot formulation comprised of a thermoresponsive elastin-like polypeptide (ELP) and FKBP, the cognate receptor for Rapa (5FV). Depot formation was confirmed in excised whole LG using cleared tissue and observation by both laser-scanning confocal and lightsheet microscopy. The LG depot was evaluated for safety, efficacy, and intra-LG pharmacokinetics in the NOD mouse disease model. Intra-LG injection with the depot formulation (5FV) retained Rapa in the LG for a mean residence time (MRT) of 75.6 h compared to Rapa delivery complexed with a soluble carrier control (5FA), which had a MRT of 11.7 h in the LG. Compared to systemic delivery of Rapa every other day for 2 weeks (seven doses), a single intra-LG depot of Rapa representing 16-fold less total drug was sufficient to inhibit LG inflammation and improve tear production. This treatment modality further reduced markers of hyperglycemia and hyperlipidemia while showing no evidence of necrosis or fibrosis in the LG. This approach represents a potential new therapy for SS-related autoimmune dacryoadenitis, which may be adapted for local delivery at other sites of inflammation; furthermore, these findings reveal the utility of optical imaging for monitoring the disposition of locally administered therapeutics.