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ID PMID Title PublicationDate abstract
33842651 Evaluating safety and compatibility of anti-tumor necrosis factor therapy in patients with 2021 Mar Inhibition of the proinflammatory cytokine tumor necrosis factor alpha (TNFα) has been utilized as a treatment strategy for a variety of immune-mediated inflammatory disorders (IMID), including rheumatoid arthritis, Crohn's disease and psoriasis. A wide array of biologic therapies targeting the TNFα molecule, including etanercept, infliximab, certolizumab, golimumab and adalimumab, are routinely used in the care of patients with these conditions. In addition to their therapeutic potential, anti-TNFα agents commonly induce the formation of autoantibodies such as anti-nuclear antibodies and anti-double stranded DNA antibodies; however, the vast majority of these are of IgM isotype and of unclear clinical significance, uncommonly leading to drug-induced autoimmune disease. For these reasons, TNFα inhibition has been a controversial strategy in the treatment of primary connective tissue disorders (CTDs). However, as new therapeutics continue to be developed for the management of CTDs, the potential utility for anti-TNFα agents has become of great interest, demonstrated in several recent case series and small open-label trials. We review the safety and compatibility of anti-TNFα therapy in the management of systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE), two well-studied example CTDs, as well as summarize the risks of autoantibody generation, infection, malignancy, and iatrogenic lupus flares as side effects of blocking TNFα in patients with these conditions.
33704005 FXR activation prevents liver injury induced by Tripterygium wilfordii preparations. 2021 Jun Tripterygium glycosides tablets (TGT) and Tripterygium wilfordii tablets (TWT) are the preparations of Tripterygium wilfordii used to treat rheumatoid arthritis (RA) in the clinic, but the hepatotoxicity was reported frequently. This study aimed to determine the potential toxicity mechanism of liver injury induced by the preparations of Tripterygium wilfordii in mice.Here, we performed metabolomic analysis, pathological analysis and biochemical analysis of samples from mice with liver injury induced by TGT and TWT, which revealed that liver injury was associated with bile acid metabolism disorder. Quantitative real-time PCR (QPCR) and western blot indicated that the above changes were accompanied by inhibition of farnesoid X receptor (FXR) signalling.Liver injury from TWT could be alleviated by treatment of the FXR agonist obeticholic acid (OCA) via activation of the FXR to inhibit the c-Jun N-terminal kinase (JNK) pathway and improve bile acid metabolism disorder by activating bile salt export pump (BSEP) and organic solute-transporter-β (OSTB). The data demonstrate that FXR signalling pathway plays a key role in T. wilfordii-induced liver injury, which could be alleviated by activated FXR.These results indicate that FXR activation by OCA may offer a promising therapeutic opportunity against hepatotoxicity from the preparations of T. wilfordii.
33640322 Drugs Recommended in Adult Rheumatic Diseases, But Considered for Off-Label Use in Argenti 2021 Feb 24 BACKGROUND: Off-label (OL) drug use is the prescription of a drug for indications other than those authorised in its technical datasheet. The objective of this study was to identify drugs recommended in rheumatology but considered for off-label use in Argentina. METHODS: A list of medications for certain selected rheumatic conditions was compiled. A drug was considered recommended if it was endorsed by a) at least one Argentine or Pan-American treatment guideline or consensus, or b) two international treatment guidelines, or c) one international treatment guideline and one selected textbook. Approval of these drugs for any condition in Argentina until December 31st, 2018 was explored, and medicines were divided into those with on-label indications and those considered for OL use. RESULTS: One hundred and thirty-six medications were analysed in 13 clinical conditions. Sixty-seven OL recommendations (49%) were found, and several drugs had more than one. All the conditions included the recommendation of at least 1 OL drug except osteoporosis and rheumatoid arthritis. The frequency of OL recommendations for the following conditions was 100%: calcium pyrophosphate dihydrate crystal deposition disease, polymyalgia rheumatica, Sjögren syndrome, and systemic sclerosis. The drugs with the highest number of OL recommendations were methotrexate (in 7 conditions), and glucocorticoids and mycophenolate (in 4). There were 2 OL recommendations for rituximab and 1 for abatacept. CONCLUSIONS: Almost all the rheumatic disorders analysed involved the recommendation of at least 1 OL medication, and in 4 conditions all the recommendations were OL. Most OL drugs recommended in rheumatology are neither biological nor small-molecule therapies.
33616421 Reverse total shoulder arthroplasty. 2021 May AIMS: This systematic review asked which patterns of complications are associated with the three reverse total shoulder arthroplasty (RTSA) prosthetic designs, as classified by Routman et al, in patients undergoing RTSA for the management of cuff tear arthropathy, massive cuff tear, osteoarthritis, and rheumatoid arthritis. The three implant design philosophies investigated were medial glenoid/medial humerus (MGMH), medial glenoid/lateral humerus (MGLH), and lateral glenoid/medial humerus (LGMH). METHODS: A systematic review of the literature was performed via a search of MEDLINE and Embase. Two reviewers extracted data on complication occurrence and patient-reported outcome measures (PROMs). Meta-analysis was conducted on the reported proportion of complications, weighted by sample size, and PROMs were pooled using the reported standardized mean difference (SMD). Quality of methodology was assessed using Wylde's non-summative four-point system. The study was registered with PROSPERO (CRD42020193041). RESULTS: A total of 42 studies met the inclusion and exclusion criteria. Rates of scapular notching were found to be significantly higher in MGMH implants (52% (95% confidence interval (CI) 40 to 63)) compared with MGLH ((18% (95% CI 6 to 34)) and LGMH (12% (95% CI 3 to 26)). Higher rates of glenoid loosening were seen in MGMH implants (6% (95% CI 3 to 10)) than in MGLH implants (0% (95% CI 0 to 2)). However, strength of evidence for this finding was low. No significant differences were identified in any other complication, and there were no significant differences observed in PROMs between implant philosophies. CONCLUSION: This systematic review has found significant improvement in PROMS and low complication rates across the implant philosophies studied. Scapular notching was the only complication found definitely to have significantly higher prevalence with the MGMH implant design. Cite this article: Bone Joint J 2021;103-B(5):813-821.
33520995 Modeling Inflammation in Zebrafish for the Development of Anti-inflammatory Drugs. 2020 Dysregulation of the inflammatory response in humans can lead to various inflammatory diseases, like asthma and rheumatoid arthritis. The innate branch of the immune system, including macrophage and neutrophil functions, plays a critical role in all inflammatory diseases. This part of the immune system is well-conserved between humans and the zebrafish, which has emerged as a powerful animal model for inflammation, because it offers the possibility to image and study inflammatory responses in vivo at the early life stages. This review focuses on different inflammation models established in zebrafish, and how they are being used for the development of novel anti-inflammatory drugs. The most commonly used model is the tail fin amputation model, in which part of the tail fin of a zebrafish larva is clipped. This model has been used to study fundamental aspects of the inflammatory response, like the role of specific signaling pathways, the migration of leukocytes, and the interaction between different immune cells, and has also been used to screen libraries of natural compounds, approved drugs, and well-characterized pathway inhibitors. In other models the inflammation is induced by chemical treatment, such as lipopolysaccharide (LPS), leukotriene B4 (LTB4), and copper, and some chemical-induced models, such as treatment with trinitrobenzene sulfonic acid (TNBS), specifically model inflammation in the gastro-intestinal tract. Two mutant zebrafish lines, carrying a mutation in the hepatocyte growth factor activator inhibitor 1a gene (hai1a) and the cdp-diacylglycerolinositol 3-phosphatidyltransferase (cdipt) gene, show an inflammatory phenotype, and they provide interesting model systems for studying inflammation. These zebrafish inflammation models are often used to study the anti-inflammatory effects of glucocorticoids, to increase our understanding of the mechanism of action of this class of drugs and to develop novel glucocorticoid drugs. In this review, an overview is provided of the available inflammation models in zebrafish, and how they are used to unravel molecular mechanisms underlying the inflammatory response and to screen for novel anti-inflammatory drugs.
33519809 Vagus Nerve Stimulation Decreases Pancreatitis Severity in Mice. 2020 BACKGROUND: Vagus nerve stimulation (VNS) is effective in reducing inflammation in various diseases, such as rheumatoid arthritis, colitis and acute kidney injury. The anti-inflammatory effect of vagus nerve in these diseases necessitates the interactions of neural activation and α7 nicotinic acetylcholine receptors (α7nAChRs) on splenic macrophages. In this study, we aimed to investigate the effect of VNS on severity in experimental acute pancreatitis (AP). METHODS: Two independent AP models were used, which induced in ICR mice with caerulein or pancreatic duct ligation (PDL). Thirty minutes after modeling, the left cervical carotid sheath containing the vagus nerve was electrically stimulated for 2 min. Plasma lipase and amylase activities, TNF-α levels and pancreas histologic damage were evaluated. In caerulein mice, the percentages of α7nAChR(+) macrophage in pancreas and spleen were assessed by flow cytometry. Furthermore, splenectomy and adoptive transfer of VNS-conditioned α7nAChR splenocytes were performed in caerulein mice to evaluate the role of spleen in the protective effect of VNS. RESULTS: VNS reduced plasma lipase and amylase activities, blunted the concentrations of TNF-α and protected against pancreas histologic damage in two AP models. Survival rates were improved in the PDL model after VNS. In caerulein AP mice, VNS increased the percentages of α7nAChR(+) macrophages in pancreas and spleen. Adoptive transfer of VNS-treated α7nAChR splenocytes provided protection against pancreatitis in recipient mice. However, splenectomy did not abolish the protective effect of VNS. CONCLUSIONS: VNS reduces disease severity and attenuates inflammation in AP mice. This effect is independent of spleen and is probably related to α7nAChR on macrophage.
33516901 Evaluation of triclosan exposures on secretion of pro-inflammatory cytokines from human im 2021 Apr Triclosan (TCS) is widely used in personal hygiene products, such as mouthwash and toothpaste, and is found in human tissues. Interleukin (IL)-1 beta (IL-1β), IL-6, tumor necrosis factor alpha (TNFα), and interferon gamma (IFNγ) are pro-inflammatory cytokines and inappropriately elevated levels of each have been associated with pathologies including rheumatoid arthritis and certain cancers. Here we examine effects of TCS on the secretion of the pro-inflammatory cytokines from human immune cell preparations. TCS at concentrations between 0.05-5 μM consistently increased the secretion of IL-1β, IL-6, and TNFα within 24 h of exposure and the increases often maintained out to 6 days of exposure. TCS also induced increases in IFNγ secretion, however the increases were most consistent after 48 h of exposure rather than within 24 h. Additionally, a role for both p44/42 and p38 MAPK in TCS-stimulated increases in IL-1β was seen in cells from some donors.
33412391 Role of Forkhead box O3a transcription factor in autoimmune diseases. 2021 Mar Forkhead box O3a (FOXO3a) transcription factor, the most important member of Forkhead box O family, is closely related to cell proliferation, apoptosis, autophagy, oxidative stress and aging. The downregulation of FOXO3a has been verified to be associated with the poor prognosis, severer malignancy and chemoresistance in several human cancers. The activity of FOXO3a mainly regulated by phosphorylation of protein kinase B. FOXO3a plays a vital role in promoting the apoptosis of immune cells. FOXO3a could also modulate the activation, differentiation and function of T cells, regulate the proliferation and function of B cells, and mediate dendritic cells tolerance and immunity. FOXO3a accommodates the immune response through targeting nuclear factor kappa-B and FOXP3, as well as regulating the expression of cytokines. Besides, FOXO3a participates in intercellular interactions. FOXO3a inhibits dendritic cells from producing interleukin-6, which inhibits B-cell lymphoma-2 (BCL-2) and BCL-XL expression, thereby sparing resting T cells from apoptosis and increasing the survival of antigen-stimulated T cells. Recently, plentiful evidences further illustrated the significance of FOXO3a in the pathogenesis of autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, ankylosing spondylitis, myositis, multiple sclerosis, and systemic sclerosis. In this review, we focused on the biological function of FOXO3a and related signaling pathways regarding immune system, and summarized the potential role of FOXO3a in the pathogenesis, progress and therapeutic potential of autoimmune diseases.
33407883 Interleukin-22 and connective tissue diseases: emerging role in pathogenesis and therapy. 2021 Jan 6 Interleukin-22 (IL-22), a member of the IL-10 family of cytokines, is produced by a number of immune cells involved in the immune microenvironment of the body. IL-22 plays its pivotal roles by binding to the IL-22 receptor complex (IL-22R) and subsequently activating the IL-22R downstream signalling pathway. It has recently been reported that IL-22 also contributes to the pathogenesis of many connective tissue diseases (CTDs). In this review, we will discuss the role of IL-22 in several CTDs, such as system lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, systemic sclerosis and dermatomyositis, suggesting that IL-22 may be a potential therapeutic target in CTDs.
33315186 Sjögren's Syndrome Associated With Thrombotic Thrombocytopenic Purpura: A Case-Based Revi 2021 Mar OBJECTIVE: To review all published cases of the rare association between thrombotic thrombocytopenic purpura (TTP) and Sjögren's syndrome (SS). The authors report an additional case of this unique association. METHODS: Systematic review of the literature and a case report. The database were articles published in PubMed/MEDLINE, Web of Science, LILACS, and SciELO, registered from 1966 to August 2020. The DESH terms were "Sjögren's syndrome" and "thrombotic thrombocytopenic purpura," without language limitation. RESULTS: Most patients were female (88%), and the age varied from 30 to 75 years old. Concerning the sequence of disease appearance, SS followed by TTP was seen in seven articles, TTP and SS in three, and simultaneous appearance of both diseases in three studies. Primary SS was observed in 16 patients, and secondary SS was detected in two cases: dermatomyositis and rheumatoid arthritis. Anemia was the most common TTP manifestation, followed by thrombocytopenia, fever, consciousness alteration, renal impairment, and schistocytes' appearance on a blood smear. Treatment involved plasmapheresis, plasma exchange, rituximab, glucocorticoid, and cyclophosphamide. A good outcome was noted in most studies; few patients died. CONCLUSIONS: TTP is a rare manifestation associated with SS. After the TTP diagnosis, plasmapheresis and/or plasma exchange should be immediately implemented.
32964777 Prevalence of autoimmune disorders among bladder pain syndrome patients' relatives. 2021 Feb PURPOSE: Possible genetic background and autoimmune etiology of Bladder Pain Syndrome (BPS, formerly Interstitial Cystitis, IC) has been suggested. We studied whether familial clustering of BPS, other autoimmune diseases or fibromyalgia exist among BPS patients' genetically close relatives; possibly reflecting some common predisposing genetic background of these diseases. MATERIALS AND METHODS: Altogether 420 first- or second-degree relatives of 94 BPS patients fulfilling the NIDDK criteria were asked to fill in a survey on the self-reported diagnosis of urinary tract diseases, fibromyalgia and 23 autoimmune diseases, together with filling the O'Leary-Sant symptom score. The ones with high symptom scores were interviewed and, if necessary, referred to a further clinical consultation. The prevalence of other diseases was compared to previously published prevalence percentages. RESULTS: 334 (80%) of 420 family members returned the questionnaire. Only one of the relatives fulfilled the NIDDK criteria, and one sibling pair among the original BPS patients was found. Asthma, ulcerative colitis, fibromyalgia, iritis and rheumatoid arthritis were more common in the study population than in the reference populations. The reported prevalence of atopic dermatitis and rhinoconjunctivitis causing allergies were lower. In addition, the results show that the O'Leary-Sant symptom score is not reliable in screening for new BPS cases. CONCLUSIONS: Our study suggests that in BPS patients' families, fibromyalgia and autoimmune diseases including asthma, and especially the non-allergic form of asthma, may be over-represented.
32811217 Contraceptive practices in women with chronic medical conditions. 2021 May Contraception in women with severe medical conditions is a potential measure to reduce maternal mortality. We sought to determine the contraceptive use in women with medical conditions at the University Hospital of the West Indies (UHWI) in Jamaica to determine if there is room for improvement in contraceptive use. Participants were identified from the medical out-patient departments and questionnaires administered. Two hundred and sixty females between 18 and 44 years with varied chronic medical conditions were included. Those included were systemic lupus erythematosus (SLE), diabetes, hypertension (HTN), thyroid disease, cardiac and renal disease. The total current use of contraception was 58.4%, while 41.6% were not on contraceptives. The use of barrier methods and long-acting reversible contraceptives (LARCs) was 71% and 10%, respectively. The current use of contraception in patients with sickle cell disease (SCD) was 84% (p=.004) and in rheumatoid arthritis (RA), 14% (p=.028). Fifty-eight (58, 24.2%) of the women were using two or more methods of contraception. There is a role for improving contraceptive use among women with medical conditions as they are at increased risk of pregnancy complications.IMPACT STATEMENTWhat is already known on this subject? Women with medical comorbidities significantly contribute to both direct and indirect causes of maternal mortality. Contraception may play an integral role in reducing the risk of dying in chronically ill women; however, the use of contraception in this group is often suboptimal.What the results of this study add? This study adds to the literature that in this high-risk group, there is an underuse of long-acting reversible contraceptives, which is ideal for this population.What the implications are of these findings for clinical practice or further research? The results will provide evidence that this high-risk group of women should be targeted and counselled regarding their risk of morbidity and mortality in pregnancy as well as contraception use while their condition is optimised. From this evidence, services may be put in place in institutions, especially in low-resource settings.
32683662 The potential effect of Ramadan fasting on musculoskeletal diseases: new perspectives. 2021 Mar Ramadan, the ninth month of the Muslim lunar calendar, is a period of intermittent fasting alternated with moments of refeeding. The last decades have seen a growing number of reports that examine the potential effect of Ramadan intermittent fasting (RIF) on chronic musculoskeletal disorders. In this paper, we reviewed data that assessed the relationship of intermittent diurnal fasting during Ramadan with rheumatic diseases. Currently, recent evidence indicates that RIF may attenuate the inflammatory state by suppressing pro-inflammatory cytokine expression and reducing the body fat and the circulating levels of leukocytes. Therefore, it may be a promising non-pharmacological approach for managing the course of rheumatic inflammatory diseases. Despite differences between studies in daily fasting duration and dietary norms, there appears to be a consensus that most of the patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA) who fasted Ramadan experienced relief of their symptoms. Nevertheless, further clinical trials are required to assess the effect of RIF on other musculoskeletal and bone disorders. Additionally, we evaluated the impact of RIF on chronic medication intake. Even if a few studies on this issue are available, the primary outcomes indicate that RIF does not significantly impair either compliance or tolerance to chronic medications. These findings may give some reassurance to patients with a specific fear of drug intake during this month. Key Points • Intermittent diurnal fasting during Ramadan can modulate the inflammatory status through the down-regulation of metabolic syndrome, the reduction of pro-inflammatory cytokines, and the reduction of circulating levels of leukocytes • Ramadan intermittent fasting (RIF) can effectively improve the activity of rheumatic inflammatory diseases. • Although further studies are still required, there seems no harm for patients with gout to participate in RIF. • Primary outcomes indicate that RIF may be a promising non-pharmacological intervention for the management of patients with osteoarthritis and osteoporosis.
29939664 Morvan Syndrome. 2022 Jan Morvan syndrome or Morvan’s fibrillary chorea (MFC) is a rare constellation of neurological symptoms, consisting of peripheral nerve hyperexcitability, autonomic instability, and encephalopathy often associated with autoantibodies to voltage-gated potassium channel complexes (VGKCs). On 12 April 1890, the French physician, Dr. Augustine Marie Morvan first published a novel description of this neurological syndrome in La Gazette Hebdomadaire de Medecine et de Chirurgie.  He called it “la choree fibrillaire,” which we now know as Morvan syndrome. There have been approximately 60 cases published in the French and other literature but only a few in English literature since then. See table 1 in media section at the end of this script for a review and comparison of the varied clinical features and clinical outcomes in 20 such cases reported in English literature.                                                                                                                                    As per table 1, Morvan syndrome is predominantly a male-dominant entity with a male to female ratio of 19 to 1. The only female case was a rheumatoid arthritis patient on gold therapy who developed mild Morvan syndrome features, and whose condition reverted once treatment was discontinued. Insomnia, hyperhidrosis, dysautonomia, and myokymia were consistent findings noted in 100% (all 20) of the patients. Whereas, hallucinations were seen in 75% (15) of the patients and anti-voltage-gated potassium channel antibodies (VGKC) were observed in 45% (9) of the patients. Another very consistent finding was the conspicuous absence of seizures in 100% (all 20) of the cases and benign findings on MRI in 100% (all 20) in contrast to Limbic encephalitis where seizures and temporal lobe structural abnormalities on MRI are classic findings. Myokymia was seen in 100% (all 20) of the patients, and it was confirmed in most 80%(16) cases with EMG studies which showed spontaneous, either repetitive or continuous muscle activity in the form of fasciculations which were a combination doublet, triplet, multiplet, or neuromyotonic discharges. Other sporadic findings were elevated manganese levels in 5% (1), oligoclonal bands in cerebrospinal fluid (CSF) in 15% (3), thymoma in 40% (8), Acetylcholine receptor (AchR) antibodies in 30% (6) of patients. However, AchR antibodies in association with myasthenic features were seen in only 10% (2) of the patients. Twenty percent (4) of the patients had AchR antibodies without myasthenic features. Treatment modalities tried with varied effectiveness were thymectomy in 25% (5), anticonvulsant therapy in 45% (9), immunosuppression in 50% (10), and IVIG in 20% (4) of the patients. The most effective treatment was plasma exchange which was tried in 55% (11) of the patients, all of whom except one patient showed dramatic improvement. Treatment effectiveness was even more significant when immunosuppression and plasma exchange was tried together. Death was the outcome in only 20% (4) of the patients.
33493312 Open-label phase 3 study of intravenous golimumab in patients with polyarticular juvenile 2021 Oct 2 OBJECTIVES: To assess efficacy, pharmacokinetics (PK) and safety of intravenous (i.v.) golimumab in patients with polyarticular-course JIA (pc-JIA). METHODS: Children aged 2 to <18 years with active pc-JIA despite MTX therapy for ≥2 months received 80 mg/m2 golimumab at weeks 0, 4, then every 8 weeks through week 52 plus MTX weekly through week 28. The primary and major secondary endpoints were PK exposure and model-predicted steady-state area under the curve (AUCss) over an 8-week dosing interval at weeks 28 and 52, respectively. JIA ACR response and safety were also assessed. RESULTS: In total, 127 children were treated with i.v. golimumab. JIA ACR 30, 50, 70, and 90 response rates were 84%, 80%, 70% and 47%, respectively, at week 28 and were maintained through week 52. Golimumab serum concentrations and AUCss were 0.40 µg/ml and 399 µg ⋅ day/ml at week 28. PK exposure was maintained at week 52. Steady-state trough golimumab concentrations and AUCss were consistent across age categories and comparable to i.v. golimumab dosed 2 mg/kg in adults with rheumatoid arthritis. Golimumab antibodies and neutralizing antibodies were detected via a highly sensitive drug-tolerant assay in 31% (39/125) and 19% (24/125) of patients, respectively. Median trough golimumab concentration was lower in antibody-positive vs antibody-negative patients. Serious infections were reported in 6% of patients, including one death due to septic shock. CONCLUSION: Body surface area-based dosing of i.v. golimumab was well tolerated and provided adequate PK exposure for clinical efficacy in paediatric patients with active pc-JIA.ClinicalTrials.gov number NCT02277444.
33904145 Patient-Powered Research Networks of the Autoimmune Research Collaborative: Rationale, Cap 2021 Nov Patient-Powered Research Networks (PPRNs) are US-based registry infrastructures co-created by advocacy groups, patient research partners, academic investigators, and other healthcare stakeholders. Patient-Powered Research Networks collect information directly from patients to conduct and disseminate the results of patient-centered/powered research that helps patients make more informed decisions about their healthcare. Patient-Powered Research Networks gather and utilize real-world data and patient-reported outcomes to conduct comparative effectiveness, safety, and other research, and leverage the Internet to accomplish this effectively and efficiently. Four PPRNs focused on autoimmune and immune-mediated conditions formed the Autoimmune Research Collaborative: ArthritisPower (rheumatoid arthritis, spondyloarthritis, and other rheumatic and musculoskeletal diseases), IBD Partners (inflammatory bowel disease), iConquerMS (multiple sclerosis), and the Vasculitis PPRN (vasculitis). The Autoimmune Research Collaborative aims to inform the healthcare decision making of patients, care partners, and other stakeholders, such as clinicians, regulators, and payers. Illustrated by practical applications from the Autoimmune Research Collaborative and its constituent PPRNs, this article discusses the shared capacities and challenges of the PPRN model, and the opportunities presented by collaborating across autoimmune conditions to design, conduct, and disseminate patient-centered outcomes research.
34386009 Transcriptome Analysis of CCR9+ T Helper Cells From Primary Sjögren's Syndrome Patients I 2021 INTRODUCTION: CCR9+ Tfh-like pathogenic T helper (Th) cells are elevated in patients with primary Sjögren's syndrome (pSS) and indicated to play a role in pSS immunopathology. Here we delineate the CCR9+ Th cell-specific transcriptome to study the molecular dysregulation of these cells in pSS patients. METHODS: CCR9+, CXCR5+ and CCR9-CXCR5- Th cells from blood of 7 healthy controls (HC) and 7 pSS patients were FACS sorted and RNA sequencing was performed. Computational analysis was used to identify differentially expressed genes (DEGs), coherent gene expression networks and differentially regulated pathways. Target genes were replicated in additional cohorts. RESULTS: 5131 genes were differentially expressed between CCR9+ and CXCR5+ Th cells; 6493 and 4783 between CCR9+ and CCR9-CXCR5- and between CXCR5+ and CCR9-CXCR5-, respectively. In the CCR9+ Th cell subset 2777 DEGs were identified between HC and pSS patients, 1416 and 1077 in the CXCR5+ and CCR9-CXCR5- subsets, respectively. One gene network was selected based on eigengene expression differences between the Th cell subsets and pathways enriched for genes involved in migration and adhesion, cytokine and chemokine production. Selected DEGs of interest (HOPX, SOX4, ITGAE, ITGA1, NCR3, ABCB1, C3AR1, NT5E, CCR5 and CCL5) from this module were validated and found upregulated in blood CCR9+ Th cells, but were similarly expressed in HC and pSS patients. Increased frequencies of CCR9+ Th cells were shown to express higher levels of CCL5 than CXCR5+ and CCR9-CXCR5- Th cells, with the highest expression confined to effector CCR9+ Th cells. Antigenic triggering and stimulation with IL-7 of the Th cell subsets co-cultured with monocytes strongly induced CCL5 secretion in CCR9+ Th cell cocultures. Additionally, effector CCR9+ Th cells rapidly released CCL5 and secreted the highest CCL5 levels upon stimulation. CONCLUSION: Transcriptomic analysis of circulating CCR9+ Th cells reveals CCR9-specific pathways involved in effector T cell function equally expressed in pSS patients and HC. Given the increased numbers of CCR9+ Th cells in the blood and inflamed glands of pSS patients and presence of inflammatory stimuli to activate these cells this suggests that CCR9-specific functions, such as cell recruitment upon CCL5 secretion, could significantly contribute to immunopathology in pSS.
34869435 Juvenile Idiopathic Arthritis and COVID-19 Pandemic: Good Compliance With Treatment, Reluc 2021 Objective: The SARS-CoV-2 pandemic has induced an exceptional sanitary crisis, potentially having an impact on treatment continuation, for juvenile idiopathic arthritis (JIA) patients receiving immunosuppressive therapies. After national lockdowns, many patients were also concerned about their safety at school. We evaluated the impact of the pandemic on the optimal continuation of treatment and on the return to school in JIA patients. Methods: JIA patients under 18 years of age, usually treated with disease-modifying anti-rheumatic drugs (DMARDs) were prospectively included during their outpatient visit and completed a standardized questionnaire. The primary outcome was DMARD treatment modification in relation to the context of the pandemic but we also evaluated the pandemic's impact on the schooling. Results: One hundred and seventy three patients from 8 different expert centers were included between May and August 2020. Their mean age was 11.6 years (± 4.1 years), and most of them 31.2% (54/173) had a rheumatoid factor-negative polyarticular JIA. Fifty percent (86/172) were treated with methotrexate, and 72.5% (124/171) were treated with bDMARDs. DMARD treatment modification in relation to the pandemic was observed in 4.0% (7/173) of participants. 49.1% (81/165) of the patients did not return to school due to a personal/parental decision in 69.9% (55/81) of cases. Two patients were diagnosed positive for SARS-CoV-2 infection. Conclusion: This study suggests that JIA patients treated with DMARDs continued their treatment during the pandemic and were rarely affected by symptomatic COVID-19. In contrast, parents' reluctance was a major obstacle for returning to school. Therefore, more solidified school reopening strategies should be developed.
32248649 Ultrasound-Guided Biopsy of Suspected Salivary Gland Lymphoma in Sjögren's Syndrome. 2021 Jun OBJECTIVE: To evaluate the safety and utility of core needle biopsy (CNB) for diagnosis of salivary gland lymphoma in Sjögren's syndrome (SS). METHODS: We analyzed data from consecutive SS patients who underwent ultrasound-guided major salivary gland CNB for lymphoma diagnosis and determined whether CNB yielded an actionable diagnosis without need for further intervention. RESULTS: CNBs were performed in 24 patients to evaluate discrete parotid (n = 6) or submandibular (n = 2) gland masses or diffuse enlargement (n = 16; 15 parotid). One patient had 3 CNBs of the same mass. Of the 26 CNBs, 24 included flow cytometry, using CNB and/or fine needle aspirate material, and 14 targeted sonographically identified focal lesions. No patient reported complications. In the 23 patients with 1 CNB, final diagnoses were marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT; n = 6), atypical lymphoid infiltration (n = 3), benign lymphoepithelial sialadenitis (n = 9), normal gland tissue (n = 4), and lymphoepithelial cyst (n = 1). In the patient with serial CNBs, the initial one without flow cytometry was benign, but the next 2 showed atypical lymphoid infiltration. Monoclonal lymphoid infiltration was detected in 12 patients: 6 with MALT lymphoma, 3 were benign, and 3 with atypical lymphoid infiltration. Of the latter 3, 1 was treated with rituximab and 2 with expectant observation. The diagnosis changed from atypical lymphoid infiltration to MALT lymphoma in 1 patient following biopsy of inguinal adenopathy 6 months post-CNB. CNB provided actionable results and avoided open excisional biopsies in all cases. CONCLUSION: CNB is safe and useful in the evaluation of suspected salivary gland lymphoma in SS.
33390490 Immediate Amelioration of Severe Respiratory Distress in Sjögren's Syndrome with COVID-19 2021 Feb 15 The coronavirus disease 2019 (COVID-19) pandemic has become an urgent global health issue. An older age and underlying conditions, such as diabetes, have been reported as risk factors, but whether or not autoimmune diseases increase the risk remains unknown. An 85-year-old man with Sjögren's syndrome developed a severe COVID-19 infection that required oxygen supplementation. After discussing the goals of care with him and his wife, off-label tocilizumab was given concomitantly, resulting in a rapid improvement in his symptoms and respiratory failure. This patient represents a supplementary case confirming the efficacy and safety of tocilizumab for COVID-19 in elderly patients with autoimmune diseases.