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ID PMID Title PublicationDate abstract
33584670 CD8(+) T Lymphocytes: Crucial Players in Sjögren's Syndrome. 2020 Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease associated with damage to multiple organs and glands. The most common clinical manifestations are dry eyes, dry mouth, and enlarged salivary glands. Currently, CD4(+) T lymphocytes are considered to be key factors in the immunopathogenesis of pSS, but various studies have shown that CD8(+) T lymphocytes contribute to acinar injury in the exocrine glands. Therefore, in this review, we discussed the classification and features of CD8(+) T lymphocytes, specifically describing the role of CD8(+) T lymphocytes in disease pathophysiology. Furthermore, we presented treatment strategies targeting CD8(+) T cells to capitalize on the pathogenic and regulatory potential of CD8(+) T lymphocytes in SS to provide promising new strategies for this inflammatory disease.
32581160 Sjögren's Syndrome as an Immune-related Adverse Event of Nivolumab Treatment for Gastric 2020 Oct 15 Immune checkpoint inhibitors can affect any organ, including the salivary glands. A case of Sjögren's syndrome (SjS) induced by nivolumab for the treatment of gastric cancer is herein presented. Nivolumab treatment caused marked tumor shrinkage, but xerostomia developed after two cycles. It took 3 months after symptom onset to confirm the diagnosis of SjS. Prednisolone and pilocarpine hydrochloride did not relieve the symptoms. SjS is a relatively rare immune-related adverse event that might sometimes be overlooked. Since SjS can severely impair a patient's quality of life, oncologists should not miss any signs of salivary gland hypofunction and cooperate with specialists for SjS.
32044981 Vaginal dryness in primary Sjögren's syndrome: a histopathological case-control study. 2020 Oct 1 OBJECTIVE: The aim was to study clinical, histopathological and immunological changes in the vagina and cervix of women with primary SS, which might explain vaginal dryness. METHODS: We included 10 pre-menopausal female primary SS patients with vaginal dryness and 10 pre-menopausal controls undergoing a laparoscopic procedure. The vaginal health index was recorded. Multiplex immunoassays and flow cytometry were performed on endocervical swab and cervicovaginal lavage samples to evaluate cellular and soluble immune markers. Mid-vaginal and endocervical biopsies were taken and stained for various leucocyte markers, caldesmon (smooth muscle cells), avian V-ets erythroblastosis virus E26 oncogene homologue (ERG; endothelial cells) and anti-podoplanin (lymphatic endothelium). The number of positive pixels per square micrometre was calculated. RESULTS: One patient was excluded because of Clamydia trachomatis, and two controls were excluded because of endometriosis observed during their laparoscopy. Vaginal health was impaired in primary SS. CD45+ cells were increased in vaginal biopsies of women with primary SS compared with controls. Infiltrates were predominantly located in the peri-epithelial region, and mostly consisted of CD3+ lymphocytes. In the endocervix, CD45+ infiltrates were present in patients and in controls, but a higher number of B lymphocytes was seen in primary SS. Vascular smooth muscle cells were decreased in the vagina of primary SS patients. No differences were found in leucocyte subsets in the vaginal and endocervical lumen. CXCL10 was increased in endocervical swab samples of primary SS patients. CONCLUSION: Women with primary SS show impaired vaginal health and increased lymphocytic infiltration in the vagina compared with controls. Vaginal dryness in primary SS might be caused by vascular dysfunction, possibly induced by IFN-mediated pathways.
31541282 Adult-onset Still's disease with macrophage activation syndrome diagnosed and treated base 2020 Jan Adult-onset Still's disease (AOSD) is a relatively rare systemic inflammatory disorder and is diagnosed using various sets of classification criteria, with the Yamaguchi criteria as the most widely used criteria. Herein, we present the case of a 21-year-old woman admitted with a high fever, lasting for over 1 month, who did not fulfill the Yamaguchi criteria. However, by analyzing the inflammatory cytokine profile, we defined this case as AOSD based on a greatly elevated serum interleukin-18 level. In addition, we predicted the occurrence of macrophage activation syndrome by a characteristic increase in the soluble tumor necrosis factor receptor II level, which allowed a timely intervention for this malicious complication. Therefore, we suggest that cytokine profiling will be useful for the diagnosis and management of AOSD.
33232357 Assessment of mucin-related gene alterations following treatment with rebamipide ophthalmi 2020 Ocular surface mucins are thought to play vital roles in maintaining the homeostasis of the pre-ocular surface tear film. We performed ocular surface tests with impression cytology to assess the expression levels of mucin-related genes on the ocular surface in healthy eyes. In addition, we investigated alterations in mucin-related gene expression secondary to treatment with rebamipide ophthalmic suspension in patients with Sjögren's syndrome-associated dry eyes (SS-DE). Thirty-three healthy individuals (control group) and 13 patients from our hospital with SS-DE were enrolled. Impression cytology was performed using Schirmer's test paper for RNA sampling. The mRNA levels of SAM-pointed domain-containing ETS-like factor (SPDEF), mucin 5AC (MUC5AC), and mucin 16 (MUC16) were determined using a real-time reverse transcription-polymerase chain reaction. The ocular surface test was performed once for the control group, and at baseline as well as 2, 4, 8, and 12 weeks after treatment in the Sjögren's syndrome-associated dry eyes group. mRNA levels of SPDEF, MUC5AC, and MUC16 were not significantly different between the control and SS-DE groups before rebamipide ophthalmic suspension treatment. SPDEF mRNA levels in control subjects were significantly correlated with levels of MUC5AC. Among SS-DE patients, SPDEF mRNA levels were significantly increased at 2, 4, and 8 weeks after treatment compared with baseline levels. MUC16 mRNA levels were significantly decreased from baseline levels at 4 and 8 weeks post-treatment. Ocular surface test using impression cytology is a clinically useful tool for assessing mucous conditions on the ocular surface and can be used to determine the effects of instillation treatment with eye drops that affect mucin production at the ocular surface.
33184486 LncRNA and mRNA expression profile of peripheral blood mononuclear cells in primary Sjögr 2020 Nov 12 The aim of this study was to elucidate the expression profile and the potential role of long non-coding RNA (LncRNA) in the peripheral blood mononuclear cells of primary Sjögren's syndrome (pSS) patients. RNA-seq technology was used to detect the differentially expressed LncRNAs and mRNAs between five age-and sex-matched paired pSS patients and healthy control PBMCs. The selected LncRNAs were detected in the validation study by RT-qPCR in 16 paired pSS patients and healthy controls. The GO, KEGG, co-localization, and co-expression analysis were performed to enrich the potential gene functions and pathways. In this study, 44 out of 1772 LncRNAs and 1034 out of 15,424 mRNAs were expressed differentially in the PBMCs of pSS patients. LINC00426, TPTEP1-202, CYTOR, NRIR, and BISPR were validated as aberrantly expressed, and these LncRNAs strongly correlated with disease activity of pSS. GO and KEGG pathway analysis revealed the significant enrichment of biological processes, cellular components, and molecular function of the up and down-regulated mRNAs, which were mainly concentrated in the immune response and immune system processes. Co-localization and co-expression analysis also revealed that differentially expressed LncRNAs in the PBMCs of pSS were strongly correlated to the mRNA functioning associated with immune response and cell metastasis. Numerous LncRNAs and mRNAs were found differentially expressed in the PBMCs of pSS patients, especially NRIR and BISPR; they interacted with the co-localized and co-expressed mRNAs, which might participate in the pathogenesis of pSS through the NF-κB, JAK-STAT, and other signaling pathways that regulate cell metastasis.
32614803 M3 muscarinic acetylcholine receptor-reactive Th17 cells in primary Sjögren's syndrome. 2020 Aug 6 M3 muscarinic acetylcholine receptor (M3R) is one of the autoantigens associated with Sjögren's syndrome (SS) and is localized in exocrine glands where disease-specific inflammation occurs. The inflammatory lesion is characterized by infiltration of CD4+ T cells, including clonally expanded Th17 cells. We undertook this study to identify circulating M3R-specific Th17 cells and to determine functional properties of those cells. Using the enzyme-linked immunospot assay (ELISpot) method, we identified M3R-reactive Th17 cells in the peripheral blood of patients with primary SS (pSS). Among 10 examined pSS patients, 10 healthy subjects (HS), and 5 IgG4-related disease (IgG4-RD) patients, M3R-reactive IL-17 secreting cells were significantly increased in 5 pSS patients specifically. The most common T cell epitope, which was analyzed and confirmed by coculture of isolated CD4+ T cells with antigen presenting cells plus M3R peptides in vitro, was peptide 83-95 of M3R. Peptide recognition was partly in an HLA-DR-restricted manner, confirmed by blocking assay. M3R-reactive Th17 cells positivity correlated with higher titers of anti-M3R antibodies, whose systemic disease activity score tended to be higher. Our studies highlight the role of tissue-specific autoantigen-derived circulating Th17 cells in pSS, for which further work might lead to antigen-specific targeted therapy.
31165348 JAK Inhibitors Suppress Innate Epigenetic Reprogramming: a Promise for Patients with Sjög 2020 Apr Pathogenesis of primary Sjögren's syndrome (SjS) remains obscure. However, recent data demonstrate the implication of epigenetic alterations in the DNA methylation/hydroxymethylation process in SjS mostly affecting genes regulated by two innate cytokines, interferon α (IFNα) and IFNγ as well as the oxidative stress pathways. The Janus kinase (JAK) signal transducer and activator of transcription (STAT) pathway is known to be activated by IFN and reactive oxygen species (ROS). This prompts us to test the potential implication of JAK/STAT signaling on DNA methylation/hydroxymethylation alterations in SjS. For this purpose, the human salivary gland (HSG) cell line was used and cells were treated with both types of IFNs and H(2)O(2) to mimic activated salivary gland epithelial cells (SGEC) as observed in SjS patients. Afterwards, the global DNA level of methylcytosine and hydroxymethylcytosine, the expression of the DNA methylating enzymes (DNMTs) and ten-eleven translocation (TETs) methyl cytosine dioxygenase that controls DNA hydroxymethylation, both at transcriptional and at protein level, as well as STAT phosphorylation and ROS status were determined. Our results showed that expression of TET3 and in turn global DNA hydroxymethylation is controlled through the induction of STAT3 mediated by IFNα, IFNγ, and H(2)O(2). On the other hand, treatment with JAK inhibitors (AG490 and ruxolitinib) reverses this process, suggesting a novel treatment pathway for patients with autoimmune diseases and Sjögren's syndrome.
31988383 Sex differences in Tfh cell help to B cells contribute to sexual dimorphism in severity of 2020 Jan 27 The study examined germinal centre (GC) reaction in lymph nodes draining inflamed joints and adjacent tissues (dLNs) in male and female Dark Agouti rat collagen type II (CII)-induced arthritis (CIA) model of rheumatoid arthritis. Female rats exhibiting the greater susceptibility to CIA mounted stronger serum CII-specific IgG response than their male counterparts. This correlated with the higher frequency of GC B cells in female compared with male dLNs. Consistently, the frequency of activated/proliferating Ki-67+ cells among dLN B cells was higher in females than in males. This correlated with the shift in dLN T follicular regulatory (Tfr)/T follicular helper (Tfh) cell ratio towards Tfh cells in females, and greater densities of CD40L and CD40 on their dLN T and B cells, respectively. The higher Tfh cell frequency in females was consistent with the greater dLN expression of mRNA for IL-21/27, the key cytokines involved in Tfh cell generation and their help to B cells. Additionally, in CII-stimulated female rat dLN cell cultures IFN-γ/IL-4 production ratio was shifted towards IFN-γ. Consistently, the serum IgG2a(b)/IgG1 CII-specific antibody ratio was shifted towards an IgG2a(b) response in females. Thus, targeting T-/B-cell interactions should be considered in putative further sex-based translational pharmacology research.
31914677 Fasciola helminth defense molecule-1 protects against experimental arthritis by inhibiting 2020 Jan An inverse correlation between helminth infection and the autoimmune disease appears to be contributed by the anti-inflammatory factors produced by these organisms. Suppressing osteoclast function without affecting the systemic immunological response is an emerging therapeutic strategy for rheumatoid arthritis (RA). We observed that a synthetic peptide corresponding to 34 amino acids of C-terminal sequence of Fasciola helminth defense molecule-1 (C-FhHDM-1) inhibited RANKL-induced osteoclast formation and lysosomal acidification with an attendant upregulation of sequestome1/p62, a negative regulator of NF-κB expression. C-FhHDM-1 also suppressed RANKL production from osteoblasts. Macrophages are the major inflammatory cells in the joints of RA and C-FhHDM-1 suppressed ICAM-1 (an inflammatory surrogate) expression in these cells. In a murine model of collagen II-induced arthritis (CIA), C-FhHDM-1 improved clinical score, protected against cartilage destruction, and maintained bone mass and bone architecture of joints compared with the CIA group. C-FhHDM-1 suppressed the CIA-induced expression of TNF, IL-17, and IFN-γ in joints but not their serum levels. The peptide also had no effect on the CIA-induced suppression of T regulatory response. We conclude that C-FhHDM-1 has a joint-specific protective effect in experimental arthritis without mitigating systemic inflammation, and thus could become an adjuvant anti-arthritis therapy to prevent RA-induced osteopenia.
32613158 Patient-Initiated Follow-Up (PIFU) as reorganized support for increased patient involvemen 2020 BACKGROUND: Inflammatory Arthritis is characterized by lifelong medical treatment and an unpredictable trajectory because of the fluctuating nature of the diseases. Proactive disease management is recommended, which includes close monitoring of disease activity that traditionally has been ensured by outpatient visits to rheumatologists at various fixed intervals. Internationally, there is a growing interest in how healthcare systems can be more flexible, individual-oriented and increasingly involve patients with lifelong diseases in their own treatment and care. We aimed to explore how patients with Inflammatory Arthritis with low disease activity or remission (DAS-CRP < 2.9) experience patient involvement in a reorganized follow-up care based on flexibility and patient-initiated contact. METHODS: We conducted a qualitative study based on four mixed group discussions focused on patients with inflammatory arthritis (rheumatoid arthritis [n = 21], axial spondyloarthritis [n = 3] and psoriatic arthritis [n = 1]) participating in a reorganized follow-up care. Changes in follow-up included access to a nurse and patient-initiated follow-up (PIFU). The analysis was based on content analysis. The reporting adheres to the Consolidated Criteria for Reporting Qualitative Research (COREQ). RESULTS: In total, 25 patients (20 females (80%), mean age 61.8 [range 28-79]) participated. We identified three categories. 1) Patient-Initiated Follow-Up do not affect patients' perceived support in disease control; this refers to patients' experience of more time available through better resource utilization, as well as trust that access to professional support would be available whenever needed. The category 2) Information is valued by patients to delineate responsibilities in a new patient role reflects patients' uncertainty in the transition to PIFU, combined with confusion about the distribution of responsibilities. 3) Patients need both extended perspectives of their arthritis and focused dialogue is about expanding patients' understanding of their arthritis by interaction over time with both a rheumatologist and a rheumatology nurse in a focused dialogue to involve the patient. CONCLUSIONS: Patients participating in PIFU welcome the flexibility and involvement. However, patients need relevant information to act adequately within a new patient role. Interaction with both rheumatologists and nurses, combined with sufficient time for dialogue, broaden patients' perspective, make opportunities for action visible, and contribute to patients' ability to participate in follow-up care.
32318969 Correction to: Prevalence and risk factors associated with vertebral osteoporotic fracture 2020 Jun The authors regrets that the original published version of this article contained errors.
33520538 A Rare Case of Pyoderma Gangrenosum in a Patient With Pancreatic Neuroendocrine Tumor. 2020 Dec 28 Pyoderma gangrenosum is a rare inflammatory skin disease usually associated with an underlying internal condition. Diseases most commonly linked with pyoderma gangrenosum are inflammatory bowel disease (ulcerative colitis and Crohn's disease), rheumatoid arthritis, and hematologic malignancies such as leukemia and lymphoma. In rare instances, it can occur as a type of paraneoplastic syndrome in patients with cancer. The most common cancers associated with pyoderma gangrenosum are breast cancer followed by rectal, gastric, renal, and lung cancers. There are scarce reports of neuroendocrine tumors associated with pyoderma gangrenosum. We discuss a case of a pancreatic neuroendocrine cancer patient afflicted with pyoderma gangrenosum.
32192564 2020 New Drug Update. 2020 Apr 1 Five new drugs for medical problems often affecting older people and marketed in the United States in 2019 have been considered in this review. The uses and most important properties of these agents are discussed, and a rating for each new drug is determined using the New Drug Comparison Rating system developed by the author (DAH). Advantages, disadvantages, and other important information regarding each new drug are identified and used as the basis for determining the rating. The drugs considered include new agents indicated for the treatment of patients with Parkinson's disease, rheumatoid arthritis, chronic obstructive pulmonary disease, osteoporosis in postmenopausal women, and chronic idiopathic constipation.
32965602 Correction to: Efficacy and safety results from a randomized double-blind study comparing 2020 Nov This article originally published with the family name and given names of all authors transposed.
31936486 High-Performance Liquid Chromatography as a Novel Method for the Determination of α-Defen 2020 Jan 9 The α-defensins (AD) present in synovial fluid have been regarded as constituting the most accurate periprosthetic joint infection (PJI) biomarker. The methods most commonly used for estimating AD as a biomarker are the qualitative Synovasure(®) PJI tests, based on the technique of lateral flow, and quantitative enzyme-linked immunosorbent assay (ELISA). Here, we propose a novel test based on detecting α-defensins in synovial fluid by high-performance liquid chromatography (HPLC). Synovial fluid was collected from 157 patients diagnosed with PJI, infectious arthritis (IA), arthrosis, reactive arthritis, and rheumatoid arthritis. AD concentrations in the fluid were determined by HPLC, and these same samples were used for additional diagnostic analyses. The results were statistically processed to calculate cutoff concentrations for PJI and IA. HPLC testing showed a sensitivity of 94% and a specificity of 92% for diagnosis of PJI, and a sensitivity of 97% and a specificity of 87% for diagnosis of IA. Using HPLC, we detected in synovial fluid a combination of three α-defensins: human neutrophil peptides HNP1, HNP2, and HNP3. All measured AD concentration values shown in this work refer to the sum of these three individual concentrations. Our study shows that the HPLC method meets the conditions for measuring precise concentrations of the sum of AD and can be recommended as part of a diagnostic array for PJI and IA diagnostics. By this method, we have verified that higher levels of AD in synovial fluid can also be seen in rheumatoid illnesses, crystal arthropathies, and reactive arthritis.
32784808 Sarcopenia in Autoimmune and Rheumatic Diseases: A Comprehensive Review. 2020 Aug 7 Sarcopenia refers to a decrease in skeletal muscle mass and function. Because sarcopenia affects mortality, and causes significant disability, the clinical importance of sarcopenia is emerging. At first, sarcopenia was recognized as an age-related disease but, recently, it has been reported to be prevalent also in younger patients with autoimmune diseases. Specifically, the association of sarcopenia and autoimmune diseases such as rheumatoid arthritis has been studied in detail. Although the pathogenesis of sarcopenia in autoimmune diseases has not been elucidated, chronic inflammation is believed to contribute to sarcopenia, and moreover the pathogenesis seems to be different depending on the respective underlying disease. The definition of sarcopenia differs among studies, which limits direct comparisons. Therefore, in this review, we cover various definitions of sarcopenia used in previous studies and highlight the prevalence of sarcopenia in diverse autoimmune diseases including rheumatoid arthritis, spondyloarthritis, systemic sclerosis, inflammatory bowel disease, and autoimmune diabetes. In addition, we cover the pathogenesis and treatment of sarcopenia in autoimmune and rheumatic diseases. This review provides a comprehensive understanding of sarcopenia in various autoimmune diseases and highlights the need for a consistent definition of sarcopenia.
32613746 The impact of gender on the clinical presentation, management, and surgical outcomes of pa 2021 Apr RATIONALE, AIMS AND OBJECTIVES: Approximately 20 000 cases of septic arthritis (SA) occur in the U.S. yearly. We examined whether gender-related differences exist in the presentation, management, and outcomes of patients with native joint septic arthritis (NJSA). METHODS: This was a retrospective study of medical files of patients aged 18 years and older admitted between 1998 and 2015 to a single tertiary care hospital and diagnosed with NJSA. All study subjects had positive synovial fluid or blood cultures and each was managed surgically. Patients' charts were reviewed for demographics, comorbidities, clinical presentations, microbiology profiles, management, and outcomes. Cases of osteomyelitis, septic bursitis, prosthetic joint, and culture-negative SA were excluded. RESULTS: Of 324 NJSA patients, those who were female (n = 130; 40.1%) were significantly older at presentation than males (mean age: 63.6 vs 58.3; P = .006). Prior joint pathology was more common amongst females, including osteoarthritis (20.8% vs 12.9%; P = .04) and rheumatoid arthritis (10% vs 3.6%; P = .03). Female patients had a higher frequency of hip involvement (17.7% vs 10.8%; P = .05). No differences were observed in clinical presentations, culture results, medical management, or outcomes between genders. CONCLUSIONS: Compared to men, women with NJSA presented at an older age and had more prior joint pathology and a higher frequency of hip involvement. These differences, however, had no significant impact on the clinical presentation, medical management, or outcomes of NJSA.
32637868 First-year drug therapy of new-onset rheumatoid and undifferentiated arthritis: a nationwi 2020 BACKGROUND: In this retrospective cohort study, we evaluated the drug therapies used for early rheumatoid (RA) and undifferentiated (UA) arthritis patients. METHODS: From a nationwide register maintained by the Social Insurance Institution, information on sex, date of birth, and date of special medicine reimbursement decision for all new Finnish RA and UA patients between 2011 and 14 were collected, and their DMARD (Disease Modifying Antirheumatic Drug) purchases during the first year after the diagnosis were analyzed. RESULTS: A total of 7338 patients with early RA (67.3% female, 68.1% seropositive) and 2433 with early UA (67.8% female) were identified. DMARDs were initiated during the first month after the diagnosis to 92.0% of the patients with seropositive RA, 90.3% with seronegative RA and to 87.7% with UA (p < 0.001). Respectively, 72.1, 63.4, and 42.9% of the patients (p < 0.001) purchased methotrexate; 49.8, 35.9, and 16.0% (p < 0.001) as part of a DMARD combination during the first month. By the end of the first year after the diagnosis, self-injected biologics were purchased by 2.6, 5.3 and 3.1% (p < 0.001) of them. Only 1.4, 2.6 and 3.0% (p < 0.001) of the patients were not receiving any DMARDs. During the first year, 83.4% of the seropositive RA patients had purchased methotrexate, 50.4% sulfasalazine, 72.1% hydroxychloroquine, and 72.6% prednisolone. CONCLUSIONS: Currently, combination therapy including methotrexate is a common treatment strategy for early seropositive RA in Finland. Despite an easy access to biologics, these drugs are seldom needed during the first year after diagnosis.
32606620 Satisfaction of Patients and Physicians with Treatments for Rheumatoid Arthritis: A Popula 2020 PURPOSE: Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by chronic destructive synovitis and possible multisystem involvement. This study aimed to survey the treatment satisfaction of physicians and patients with RA, and to explore the potential factors. PATIENTS AND METHODS: This cross-sectional study was conducted in 12 centers across China between March 2018 and April 2018. The Treatment Satisfaction Questionnaire for Medication version II was used to assess the treatment satisfaction of patients and physicians. Multivariable regression analysis was used to determine the factors independently associated with treatment satisfaction of patients. RESULTS: The patients' satisfaction (n=335) with biological disease-modifying antirheumatic drugs (bDMARDs) was higher than physicians' satisfaction (n=146) regarding the side effects (95.0±14.3 vs 84.6±15.7, P<0.001) and convenience (74.6±21.2 vs 69.1±16.5, P=0.002). Among physicians, global satisfaction with bDMARDs was higher than that with conventional synthetic DMARDs (csDMARDs). The multivariable regression analysis showed that age was positively associated with satisfaction of patients, while college or above education and self-assessment of disease severity were inversely associated with satisfaction. Treatment satisfaction was associated positively with the quality of communication with the physician and inversely with treatment costs. CONCLUSION: For bDMARDs, the treatment satisfaction of patients with RA is generally higher than that of physicians'. Physicians' satisfaction with bDMARDs is higher than with csDMARDs. Age, education, disease severity, communication with the physician, and treatment costs are independently associated with the treatment satisfaction among patients. Physician-patient communication should be improved in clinical practice. Treatment costs should be taken into account when physicians make decisions.