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ID PMID Title PublicationDate abstract
33372891 Severe infections remain common in a real-world rheumatoid arthritis cohort: A simple clin 2021 Jul OBJECTIVE: This study aimed to investigate the incidence of severe infections in patients of a dedicated rheumatoid arthritis (RA) clinic, identify the associated risk factors, and derive an infection risk screening tool. METHODS: Between January and July 2019, 263 eligible patients with a diagnosis of RA were recruited retrospectively and consecutively from an RA clinic of an Australian tertiary hospital. The primary outcome was severe infection (requiring hospital admission) between January 2018 and July 2019. We collected data from medical records and pathology results. We used validated scores, such as the disease activity score of 28 joints (DAS28) and the Charlson comorbidity index, to assess the disease activity and comorbidity burden. Multivariable logistic regression was used for statistical analysis. RESULTS: A total of 45 severe infection episodes occurred in 34 (13%) patients, corresponding to 10.8 infections per 100 patient-years. Respiratory (53%) and urinary (13%) tract infections were the most common. In the multivariable analysis, significant risk factors included low lymphocyte count (odds ratio [OR], 4.08; 95% confidence interval [CI], 1.16-14.29), severe infection in the past 3 years (OR, 3.58; 95% CI, 1.28-9.97), Charlson comorbidity index >2 (OR, 2.69; 95% CI, 1.03-7.00), and higher DAS28 (OR, 1.35/0.5-unit increment; 95% CI, 1.10-1.67). A model incorporating these factors and age had an area under receiver operating characteristic curve of 0.82. CONCLUSION: To the best of our knowledge, this was one of the first Australian studies to evaluate severe infection rates in a real-world RA cohort. The rates remained high and comparable with those of the older studies. Lymphopenia, disease activity, comorbidity burden, and previous severe infection were the independent risk factors for infection. A model comprising easily assessable clinical and biological parameters has an excellent predictive potential for severe infection. Once validated, it may be developed into a screening tool to help clinicians rapidly identify the high-risk patients and inform the tailored clinical decision making.
33002981 Association of Breast Implants with Nonspecific Symptoms, Connective Tissue Diseases, and 2021 Jan 1 BACKGROUND: Given the rising media attention regarding various adverse conditions attributed to breast implants, the authors examined the association between breast implantation and the risk of being diagnosed with connective tissue diseases, allergic reactions, and nonspecific constitutional complaints in a cohort study with longitudinal follow-up. METHODS: Women enrolled in a regional military health care system between 2003 and 2012 were evaluated in this retrospective cohort study. A propensity score was generated to match women who underwent breast implantation with women who did not undergo breast implantation. The propensity score included age, social history, health care use, comorbidities, and medication use. Outcomes assessed included International Classification of Diseases, Ninth Revision, diagnoses codes for (1) nonspecific constitutional symptoms, (2) nonspecific cardiac conditions, (3) rheumatoid arthritis and systemic lupus erythematosus, (4) other connective tissue diseases, and (5) allergic reactions. RESULTS: Of 22,063 women included in the study (513 breast implants and 21,550 controls), we propensity score-matched 452 breast implant recipients with 452 nonrecipients. Odds ratios and 95 percent confidence intervals in breast implant recipients compared to nonrecipients were similar, including nonspecific constitutional symptoms (OR, 0.77; 95 percent CI, 0.53 to 1.13), nonspecific cardiac conditions (OR, 0.97; 95 percent CI, 0.69 to 1.37), rheumatoid arthritis and systemic lupus erythematosus (OR, 0.66; 95 percent CI, 0.33 to 1.31), other connective tissue diseases (OR, 1.02; 95 percent CI, 0.78 to 1.32), and allergic reactions (OR, 1.18; 95 percent CI, 0.84 to 1.66). CONCLUSIONS: Women with breast implants did not have an increased likelihood of being diagnosed with nonspecific constitutional symptoms, connective tissue disorders, and/or allergic reaction conditions. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.
32598578 The ISCCA flow protocol for the monitoring of anti-CD20 therapies in autoimmune disorders. 2021 Mar BACKGROUND: Anti-CD20 monoclonals (MoAbs) are used in a variety of autoimmune disorders. The aim is to eliminate memory B cells sustaining the tissue damage and the production of pathogenic autoantibodies, while preserving naïve cells. The disappearance of memory B cells and the repopulation by naïve cells correlate with good clinical response, while the reappearance of memory B cells and plasmablasts correlates with relapse or resistance to therapy. Anti-CD20 induce extremely low B cell levels, requiring high-resolution techniques. The immune monitoring protocol developed by ISCCA is described and validated, to provide a standardized method for the clinical decision-making process during anti-CD20 therapies in autoimmune diseases. METHODS: A 10-marker, 8-color staining panel (CD20-V450, CD45-V500c, CD4-FITC + sIgM-FITC, CD38-PE, CD3-PerCP Cy5.5, CD19-PE-Cy7, CD27-APC, CD8-APC H7 + sIgG-APC-H7) is used to identify B cells, plasma cells/blasts, naïve and memory B cells, sIgM+ and sIgG-switched memory B cells, T and NK cells, with high-sensitivity analysis (>10(6) CD45+ cells). RESULTS: After an anti-CD20 dose, the B cell level is about zero in most patients. If B cells remain virtually absent (<0.1/μl), subsetting is not reliable nor meaningful. If B cells raise >0.3-0.5/μl, subsetting is possible and informative, acquiring >1.0-1.5 × 10(6) CD45+ events. Further testings can follow the quality of B cell repopulation. If B cells become detectable (>1/μl), the prevalence of memory B cells indicates non-responsiveness or a possible relapse. CONCLUSIONS: The ISCCA Protocol is proposed for a standardized prospective monitoring of patients with autoimmune disorders, to assist the safe and rational usage of anti-CD20 therapies.
33602331 Synthesis and therapeutic potential of imidazole containing compounds. 2021 Feb 18 Imidazole is a five-membered heterocyclic moiety that possesses three carbon, two nitrogen, four hydrogen atoms, and two double bonds. It is also known as 1, 3-diazole. It contains two nitrogen atoms, in which one nitrogen bear a hydrogen atom, and the other is called pyrrole type nitrogen. The imidazole name was reported by Arthur Rudolf Hantzsch (1857-1935) in 1887. 1, 3-diazole is an amphoteric in nature i.e. it shows both acidic and basic properties. It is a white or colorless solid that is highly soluble in water and other polar solvents. Due to the presence of a positive charge on either of two nitrogen atom, it shows two equivalent tautomeric forms. Imidazole was first named glyoxaline because the first synthesis has been made by glyoxal and ammonia. It is the basic core of some natural products such as histidine, purine, histamine and DNA based structures, etc. Among the different heterocyclic compounds, imidazole is better known due to its broad range of chemical and biological properties. Imidazole has become an important synthon in the development of new drugs. The derivatives of 1, 3-diazole show different biological activities such as antibacterial, antimycobacterial, anti-inflammatory, antitumor, antidiabetic, anti-allergic, antipyretic, antiviral, antioxidant, anti-amoebic, antihelmintic, antifungal and ulcerogenic activities, etc. as reported in the literature. There are different examples of commercially available drugs in the market which contains 1, 3-diazole ring such as clemizole (antihistaminic agent), etonitazene (analgesic), enviroxime (antiviral), astemizole (antihistaminic agent), omeprazole, pantoprazole (antiulcer), thiabendazole (antihelmintic), nocodazole (antinematodal), metronidazole, nitroso-imidazole (bactericidal), megazol (trypanocidal), azathioprine (anti rheumatoid arthritis), dacarbazine (Hodgkin's disease), tinidazole, ornidazole (antiprotozoal and antibacterial), etc. This present review summarized some pharmacological activities and various kinds of synthetic routes for imidazole and their derived products.
33795795 ZIP8 exacerbates collagen-induced arthritis by increasing pathogenic T cell responses. 2021 Apr Zinc is a trace element that is essential for immune responses. Therefore, changes in cellular zinc levels in specific immune cells may influence inflammatory autoimmune diseases, such as rheumatoid arthritis (RA). However, the regulation of zinc mobilization in immune cells and its role in the pathogenesis of RA are not fully understood. Thus, we investigated the roles of zinc transporters in RA pathogenesis. We demonstrated that ZIP8 was specifically upregulated in CD4(+) T cells that infiltrated the inflamed joint and that ZIP8 deficiency in CD4(+) T cells abrogated collagen-induced arthritis. ZIP8 deficiency dramatically affected zinc influx in effector T cells and profoundly reduced T cell receptor (TCR)-mediated signaling, including NF-κB and MAPK signaling, which are pathways that are involved in T helper (Th) 17 cell differentiation. Taken together, our findings suggest that ZIP8 depletion in CD4(+) T cells attenuates TCR signaling due to insufficient cellular zinc, thereby reducing the function of effector CD4(+) T cells, including Th17 cells. Our results also suggest that targeting ZIP8 may be a useful strategy to inhibit RA development and pathogenesis.
34930431 Salivary gland ultrasonography in primary Sjögren's syndrome from diagnosis to clinical s 2021 Dec 20 BACKGROUND: To determine the diagnostic accuracy of major salivary gland ultrasonography (SGUS) in primary Sjögren's syndrome (pSS) using the novel Outcome Measures in Rheumatology Clinical Trials (OMERACT) scoring system in a large-scale multicentre study. METHODS: SGUS was conducted for 246 pSS patients, 140 control subjects with conditions other than SS and 27 healthy control subjects. The echostructure features from the parotid and submandibular glands on both sides were graded using the novel OMERACT scoring system. Receiver operating characteristic curves were used to describe the diagnostic accuracy of the scoring system for pSS. The associations between the SGUS and disease characteristics were analysed to evaluate the clinical value of SGUS for pSS. RESULTS: The US scores in the pSS group were significantly higher than those in the non-pSS group (p < 0.001). The level of diagnostic accuracy was comparable with the scores of all four glands (AUC=0.908) when only the parotid and submandibular glands on either side were scored (AUC=0.910, 0.904, respectively). The optimal cut-off value for the left (right) parotid gland and the left (right) submandibular gland was 4, with maximal sensitivity (75.6% and 77.2%, respectively) and specificity (91.6% and 92.2%, respectively). The pSS patients with positive SGUS results presented a longer disease duration, parotid enlargement, dental loss and higher levels of serological markers, such as anti-SSA, anti-SSB, positive RF, IgG and γ-globulin%. CONCLUSIONS: SGUS with the OMERACT scoring system yields high sensitivity and specificity, demonstrating high diagnostic feasibility for pSS. The SGUS may have implications for deciding disease severity and treatment efficacy.
34544497 Autoinflammation leading to autoimmunity in adult-onset Still's disease: more than simple 2021 Sep 20 BACKGROUND: Adult-onset Still's disease (AOSD) should be considered in the differential diagnosis of patients with endocarditis, with or without a cardiac decompensation. CASE PRESENTATION: We report the case of a 68-year-old Caucasian male diagnosed with AOSD after an initial acute manifestation of endocarditis with severe aortic acute manifestation of endocarditis with severe aortic insufficiency. The histological findings revealed Libman-Sacks endocarditis. He was treated with the IL-1 receptor inhibitor anakinra. Two years later the patient developed a symptomatic dilated cardiomyopathy with reduced ejection fraction (23.5%) and functional anti-beta-1-adrenergic receptor antibodies, which was initially treated with plasmapheresis; anakinra was maintained. While his AOSD symptoms responded well, our patient presented with recurrent arthritis in multiple joints, dual-energy CT showed urate deposition compatible with a gouty arthropathy. Over 7 years, he presented with recurrent episodes of arthritis and the adjustment of dosages of colchicine and febuxostat was needed. In 2018, our patient died due to a deterioration of his underlying cardiac disease. CONCLUSIONS: Only two cases with initial endocarditis prior to AOSD diagnosis have been published, and we are not aware of any other cases reporting -β1AR-Ab development with DCM and gout in the setting of AOSD treated with anakinra.
33992583 Salivary glands ultrasonography as a diagnostic aid in Sjögren syndrome: A prospective pi 2021 Aug OBJECTIVE: The aims of this pilot investigation were to calculate the levels of sensitivity and specificity of salivary glands ultrasonography (SGUS) in diagnosing Sjögren syndrome (SS) and to assess the ultrasonographic findings of parotid and submandibular glands. STUDY DESIGN: Patients diagnosed with SS or dry mouth and healthy controls were enrolled. Bilateral parotid and submandibular glands were assessed for (1) parenchymal inhomogeneity (PIH), (2) median size of the glands, (3) visibility of glandular posterior borders, and (4) size of sialolith, if present. RESULTS: This study included 34 female patients, of whom 12 had SS (35.3%), 12 had dry mouth (35.3%), and 10 were healthy controls (29.4%). Patients with SS showed higher PIH scores in all glands with the median differences being statistically higher in the right and left parotids and left submandibular glands (P < .001, P = .012, and P < .001, respectively). SGUS, with a PIH cutoff ≥2, showed a sensitivity of 100% and a specificity of 81.6% for detecting SS. The majority of SS had invisible glandular posterior borders (P < .001). Median size of the glands and size of the sialolith did not show any statistically significant differences between groups. CONCLUSIONS: SGUS is a noninvasive imaging modality with good sensitivity and specificity that might be valuable as a diagnostic aid for SS.
33912165 Higher Risk for Sjögren's Syndrome in Patients With Fibromyalgia: A Nationwide Population 2021 OBJECTIVES: Clinically, associations have been observed between Sjögren's syndrome and fibromyalgia. Nonetheless, population-based evidence evaluating the risk of Sjögren's syndrome in fibromyalgia patients is lacking. The main purpose of this retrospective cohort study was to determine the association between fibromyalgia and subsequent development of Sjögren's syndrome. METHODS: This retrospective cohort study extracted data from the Longitudinal Health Insurance Database (LHID) of the Taiwan National Health Insurance (NHI). During 2000-2012, patients with newly-diagnosed fibromyalgia (International Classification of Diseases, Ninth Revision, Clinical Modification code 729.1) were defined as the exposure cohort. Age- and gender-matched individuals without fibromyalgia were used as the comparison cohort. The adjusted hazard ratios (aHR) for the occurrence of Sjögren's syndrome in those with fibromyalgia were evaluated along with stratified analyses of different subgroups. RESULTS: Of the 149,706 subjects whose data were extracted from the LHID, 74,853 subjects had coded fibromyalgia and 74,853 control subjects were without fibromyalgia. Compared to the control group, patients with fibromyalgia had an aHR of 2.00 (95% Confidence Interval [CI], 1.52-2.61) for developing Sjögren's syndrome. In fibromyalgia patients aged 20-49 years, the aHR for future Sjögren's syndrome was 3.07 (95% CI, 1.92-4.89). CONCLUSION: Patients with fibromyalgia, both males and females, have a higher risk for developing Sjögren's syndrome than those without fibromyalgia, especially those aged 20-49 years. While managing patients, clinicians should be aware of the bidirectional association between the two diseases, which helps to understand the impact of the association on disease activity and diagnosis.
32749912 Uveal Effusion Syndrome as the Initial Manifestation of Primary Sjögren's Syndrome and Re 2021 Nov 17 Purpose: The authors report a38-year-old woman with primary Sjögren's syndrome who initially showed recurrent blurred vision caused by uveal effusion syndrome and later developed dry mouth, dry eyes, and arthralgia. During the 5-year-course of disease, the patient's 3-time-onset was all manifested as blurred vision after decreased immunity. Despite the initial absence of sufficient immunological evidence, the final presence of positive serum anti-SS-A, rheumatoid factors, ANA, and inflammatory findings in minor salivary gland biopsy indicated primary Sjögren's syndrome.Methods: Retrospective review of a case note.Conclusions: The manifestation of UES requires further exploration of its real pathogenesis, and the possibility of systemic disease should never be excluded.
34654730 Long-term Safety of Rituximab in Primary Sjögren Syndrome: The Experience of a Single Cen 2022 Feb OBJECTIVE: This work aims to evaluate the long-term safety of rituximab (RTX) in primary Sjögren syndrome (pSS) and to determine the safety and the efficacy of long-term treatment with B cell depleting therapy in pSS patients with active systemic disease. METHODS: A historical cohort study, enrolling 35 patients with pSS treated with RTX between 2008 and 2019 in a single rheumatologic unit, was performed. When patients experienced adverse events, the treatment was suspended and patients' data were recorded. RESULTS: The included patients were mainly female (91%), with a mean age of 54 years. During the time of observation, 13 patients (37.1%) suspended RTX treatment (10 cases per 100 patient-years, 95% CI 0.06-0.17). Baseline demographics, disease characteristics, European Alliance of Associations for Rheumatology (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) values, and treatment were comparable across RTX-suspended and nonsuspended groups. Patients exposed to RTX had been followed for 35.82 ± 32.56 months, and the time of observation varied from 6 to 96 months. All the patients except one experienced a significant and persisting meaningful improvement of their ESSDAI (≥ 3 points) during the long-term follow-up. For the duration of the follow-up, 13 (37%) patients discontinued RTX treatment. Four out of 13 (30.8%) discontinued the treatment after the first administration due to infusion-related reactions. During subsequent RTX courses, the main cause of withdrawal was hypogammaglobulinemia onset (7 patients). In 2 patients, hypogammaglobulinemia was associated with severe infections. CONCLUSION: Long-term RTX administration was shown to be a safe, well tolerated, and effective treatment in patients with active systemic disease, significantly reducing ESSDAI and controlling disease activity.
33769968 Genome-wide DNA methylation patterns in monocytes derived from patients with primary Sjogr 2021 Mar 26 BACKGROUND: Epigenetics, especially DNA methylation, plays an important role in the pathogenesis of primary Sjogren syndrome (pSS). Our study aimed to reveal the role of DNA methylation in peripheral monocytes of pSS patients. METHODS: A total of 11 pSS patients and five age-matched healthy controls (HCs) were included in this study. Monocytes were isolated from peripheral blood mononuclear cells using magnetic microbeads. DNA methylation profiles were generated using Human Methylation 850K BeadChips. RESULTS: In monocytes from pSS patients, we identified 2819 differentially methylated positions (DMPs), comprising 1977 hypomethylated- and 842 hypermethylated-DMPs, corresponding to 1313 unique genes when compared with HCs. IFI44L, MX1, PAARP9, and IFITM1, which influence the interferon (IFN) signaling pathway, were among the genes hypomethylated in pSS. Functional analysis of genes with a minimum of two DMPs showed involvement in antigen binding, transcriptional regulation, cell adhesion, IFN-γ pathway, type I IFN pathway, antigen presentation, Epstein-Barr virus infection, human T-lymphotropic virus type 1 virus infection, and metabolic disease-related pathways. In addition, patients with higher serum IgG levels exhibited enrichment in Notch signaling and metabolic-related pathways. Upon comparing monocytes with salivary gland epithelial cells, an important overlap was observed in the cell cycle, cell senescence, and interleukin-17 signaling pathways. The differentially methylated genes were more enriched in the ribosome- and AMP-activated protein kinase signaling pathway in anti-Ro/SSA and anti-La/SSB autoantibodies double-positive patients. CONCLUSION: Genome-wide DNA methylation profiling revealed significant differences in DNA methylation in monocytes isolated from patients with pSS.
34472811 The Pattern of Post-viral Arthritis in COVID Pandemic State: An Experience of Tertiary Car 2021 Aug BACKGROUND: Acute onset polyarthritis is a common presentation in rheumatology outpatient consultations, which include both post-infectious arthritis and autoimmune rheumatic diseases (AIRDs). COVID pandemic has added to the list of infectious agents that could result in arthritis. MATERIALS AND METHODS: The retrospective observational study was conducted at a tertiary care centre. The study included patients who presented with clinical suspicion of post-infectious arthritis between July-September 2019 and 2020. The study was extended for another 2 months to include patients who presented between October-November 2020. The patients were categorized into post-viral arthritis, post-COVID arthritis, chikungunya arthritis and AIRDs. The demographics, comorbidities, clinical presentation, examination findings and laboratory parameters and the response to treatment for each participant were collected and assessed. RESULTS: In the year 2019 and 2020 (July-Sep), the corresponding number of patients analyzed were 20 and 33. The mean duration of presentation was 1.53 (±3.10) weeks. Chikungunya arthritis was noted in 10% of patients in 2019, while it was 15.15% in 2020. Other post-viral arthritis was identified in 65% and 66.67% of patients in 2019 and 2020 respectively. In the second part of the study, 65.68% of patients were classified as post-viral arthritis, including chikungunya arthritis, post-COVID arthritis and other post-viral arthritis. Around 27% were categorized as AIRDs. Rheumatoid factor negativity and anti-nuclear antibody negativity were found to be significant (P 0.0) in categorizing the patients into post-viral arthritis group, while presence of urinary symptoms (P 0.0) classified the patients into reactive arthritis. CONCLUSION: The study revealed that the presence of chikungunya arthritis across the two years was comparable. Post-COVID arthritis needs to be considered as a potential differential in post-infectious arthritis. There are no identifiable characteristics (clinical or a simple routine laboratory parameter) that could differentiate the causes of post-infectious arthritis from AIRDs.
34919587 Outcomes of Sjögren's versus non-Sjögren's related dry eye in a longitudinal, tertiary c 2021 PURPOSE: To assess the long-term treatment outcomes of dry eye in patients with and without underlying primary Sjögren's syndrome (SS). DESIGN: Retrospective longitudinal cohort. METHODS: SS and non-SS dry eye patients with clinic visits for a minimum of 5 consecutive years at a tertiary, dedicated dry eye clinic were included. Electronic health records were reviewed to collect data regarding demographics, objective dry eye parameters, treatments utilized at baseline and final visit, and corneal complications observed during follow-up. RESULTS: Two hundred and two patients (101 SS and 101 randomly selected non-SS), with a mean follow-up of 7.1 years were included. At baseline, mean conjunctival lissamine green staining score was 2.9 and mean corneal fluorescein staining score was 2.0. At last visit, notable improvement in staining score for cornea (-1.1, P < .001) and conjunctiva (-1.8, P < .001) was seen equally in both dry eye groups. Most patients (88.1%) had an escalation of treatment by the final visit, with similar rates in both groups (P = .51). Half (48.9%) of the patients had no conjunctival staining, and a third (34.4%) had no corneal staining at their last visit. Twenty (9.9%) patients experienced a vision-threatening corneal complication, including ulcers and melt, with no difference in occurrences between the groups (P = .64). CONCLUSIONS: The majority of patients in this longitudinal, tertiary clinic-based sample demonstrated improvement in their ocular surface staining score by the final visit with escalation in treatment. Treatments used, improvement achieved, and corneal complication rates leading to loss of vision were similar in both SS and non-SS dry eye groups.
34471033 Nodular Pulmonary Amyloidosis Associated with Sjögren's Syndrome. 2022 Mar 15 Amyloidosis is a rare disease characterized by the deposition of abnormal proteins in extracellular tissues. We herein report a case with instructive radiologic features of nodular pulmonary amyloidosis associated with Sjögren's syndrome. A 67-year-old woman was referred to our department because of an abnormal chest radiograph. Chest computed tomography revealed multiple round cysts accompanied by calcified nodules. The patient was clinically diagnosed with primary Sjögren's syndrome and pathologically diagnosed with nodular pulmonary amyloidosis (light chain, kappa). Although multiple lung cysts have many etiologies, the presence of calcified nodules associated with multiple lung cysts is useful for narrowing down the differential diagnosis.
34165604 Revisiting the JOQUER trial: stratification of primary Sjögren's syndrome and the clinica 2021 Sep To re-analyse the clinical outcomes and interferon (IFN) activity data from the JOQUER trial, a phase III trial investigating hydroxychloroquine (HCQ) in patients with primary Sjögren's syndrome (pSS), after stratifying patients into putative pathobiological subgroups utilizing the Newcastle Sjögren's Stratification Tool (NSST) based on patient-reported symptoms of dryness, pain, fatigue, anxiety and depression. 107 patients were assigned to one of four subgroups using NSST at baseline-the high symptom burden (HSB), pain dominant with fatigue (PDF), dryness dominant with fatigue (DDF) and low symptom burden (LSB). Endpoints were re-analysed after stratification, testing for treatment differences within subgroups and adjusting for baseline differences using a repeated measures covariate model. The HSB subgroup (n = 32) showed a relative improvement in ESSPRI of 1.49 points (95% CI 0.54-2.43; p = 0.002) within 12 weeks in patients taking HCQ compared to placebo, with no further changes after 24 weeks. For the LSB subgroup (n = 14), the ESSPRI worsened in the placebo but not the HCQ arm after 12 weeks (mean difference 1.44, 95% CI 0.05-2.83, p = 0.042). Neither the HSB nor the LSB patients showed significant changes in IFN activity at 24 weeks. There were no significant differences in ESSPRI in the PDF (n = 39) and DDF (n = 22) patients taking HCQ. However, significant reductions in overall IFN score at 24 weeks were seen in both PDF (difference at 24 weeks; 6.41, 95% CI, 2.48-10.34, p = 0.002) and DDF (difference at 24 weeks; 7.23, 95% CI, 1.85-12.6, p = 0.009) without improvement in ESSPRI. Although the JOQUER trial reported no overall benefit from HCQ in pSS patients, stratification suggests that both HSB and LSB subgroups may respond to HCQ. However, these patients may benefit through mechanisms other than the reduction of IFN activities.
33501696 Ultra-high frequency ultrasonography (UHFUS)-guided minor salivary gland biopsy: A promisi 2021 May BACKGROUND: Sjögren's syndrome (SS) is an autoimmune disease characterized by an inflammatory infiltrate of exocrine salivary and lachrymal glands. Diagnosis is complex, and minor salivary gland biopsy and subsequent focus score (FS) calculation appear of extreme importance in the diagnostic work-up of the disease. Ultra-high frequency ultrasonography (UHFUS) is a recently introduced diagnostic technique, which is gaining an increasingly important role in intraoral imaging. This study aims at exploring the usefulness of UHFUS for obtaining valuable labial salivary gland samples to assess the histopathological features of SS patients. METHODS: Patients with clinical suspect of SS and eligible for minor salivary gland biopsy were enrolled. UHFUS scan of the lower lip was performed. Glandular echostructure was classified according to Outcome Measures in Rheumatology (OMERACT) scoring system. The glands to be sampled were selected on the basis of UHFUS evaluation and biopsied. The areas of the samples were recorded and compared with those obtained without UHFUS guidance. The correlation between UHFUS grade and labial gland FS was also assessed. RESULTS: The areas of the samples obtained with UHFUS guidance were significantly higher (7.25 ± 3.98 mm(2) ) than those obtained by conventional procedures (5.79 ± 3.49 mm(2) , P = .02). UHFUS correlated significantly with the salivary gland FS (r = .532, P = .001). CONCLUSION: UHFUS seems a promising tool in SS diagnostic algorithm, being able to provide a valuable support to the biopsy procedure. Further studies are mandatory to confirm the role of UHFUS in SS.
33622688 Impact of the COVID-19 pandemic on morbidity and mortality in patients with inflammatory j 2021 Feb 23 OBJECTIVES: To estimate absolute and relative risks for all-cause mortality and for severe COVID-19 in inflammatory joint diseases (IJDs) and with antirheumatic therapies. METHODS: Through Swedish nationwide multiregister linkages, we selected all adult patients with rheumatoid arthritis (RA, n=53 455 in March 2020), other IJDs (here: spondyloarthropathies, psoriatic arthritis and juvenile idiopathic arthritis, n=57 112), their antirheumatic drug use, and individually matched population referents. We compared annual all-cause mortality March-September 2015 through 2020 within and across cohorts, and assessed absolute and relative risks for hospitalisation, admission to intensive care and death due to COVID-19 March-September 2020, using Cox regression. RESULTS: During March-September 2020, the absolute all-cause mortality in RA and in other IJDs was higher than 2015-2019, but relative risks versus the general population (around 2 and 1.5) remained similar during 2020 compared with 2015-2019. Among patients with IJD, the risks of hospitalisation (0.5% vs 0.3% in their population referents), admission to intensive care (0.04% vs 0.03%) and death (0.10% vs 0.07%) due to COVID-19 were low. Antirheumatic drugs were not associated with increased risk of serious COVID-19 outcomes, although for certain drugs, precision was limited. CONCLUSIONS: Risks of severe COVID-19-related outcomes were increased among patients with IJDs, but risk increases were also seen for non-COVID-19 morbidity. Overall absolute and excess risks are low and the level of risk increases are largely proportionate to those in the general population, and explained by comorbidities. With possible exceptions, antirheumatic drugs do not have a major impact on these risks.
34500060 hIgDFc-Ig inhibits B cell function by regulating the BCR-Syk-Btk-NF-κB signalling pathway 2021 Nov Rheumatoid arthritis (RA) is an autoimmune disease targeting the synovium. Previous studies have found that IgD may be a potential target for the treatment of RA. We designed a new type of fusion protein, hIgDFc-Ig (DG), to block the binding of IgD to IgD receptor (IgDR). In this study, we found that DG has a significant therapeutic effect in mice with collagen-induced arthritis (CIA). DG improved the claw of irritation symptoms in these mice, inhibited the pathological changes in spleen and joint tissues, and had a moderating effect on B cell subsets at different inflammatory stages. Moreover, DG could also decrease the levels of IgA, IgD, IgM and IgG subtypes of immunoglobulin in the serum of mice with CIA. In vitro, B cell antigen receptor (BCR) knockout Ramos cells were established using the CRISPR/Cas9 technology to further study the activation of BCR signalling by IgD and the effect of DG. We found that the therapeutic effect of DG in mice with CIA may be achieved by inhibiting the activation of BCR signalling by IgD, which may be related to the activation of Igβ. In summary, DG may be a potential biological agent for the treatment of RA and it has broad application prospects in the future.
34276665 20S-Hydroxyvitamin D3, a Secosteroid Produced in Humans, Is Anti-Inflammatory and Inhibits 2021 The ability to use large doses of vitamin D3 (D3) to chronically treat autoimmune diseases such as rheumatoid arthritis (RA) is prohibitive due to its calcemic effect which can damage vital organs. Cytochrome P450scc (CYP11A1) is able to convert D3 into the noncalcemic analog 20S-hydroxyvitamin D3 [20S(OH)D3]. We demonstrate that 20S(OH)D3 markedly suppresses clinical signs of arthritis and joint damage in a mouse model of RA. Furthermore, treatment with 20S(OH)D3 reduces lymphocyte subsets such as CD4(+) T cells and CD19(+) B cells leading to a significant reduction in inflammatory cytokines. The ratio of T reg cells (CD4+CD25+Foxp3+ T cells) to CD3+CD4+ T cells is increased while there is a decrease in critical complement-fixing anti-CII antibodies. Since pro-inflammatory cytokines and antibodies against type II collagen ordinarily lead to destruction of cartilage and bone, their decline explains why arthritis is attenuated by 20(OH) D3. These results provide a basis for further consideration of 20S(OH)D3 as a potential treatment for RA and other autoimmune disorders.