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ID PMID Title PublicationDate abstract
34070409 Choline Kinase: An Unexpected Journey for a Precision Medicine Strategy in Human Diseases. 2021 May 25 Choline kinase (ChoK) is a cytosolic enzyme that catalyzes the phosphorylation of choline to form phosphorylcholine (PCho) in the presence of ATP and magnesium. ChoK is required for the synthesis of key membrane phospholipids and is involved in malignant transformation in a large variety of human tumours. Active compounds against ChoK have been identified and proposed as antitumor agents. The ChoK inhibitory and antiproliferative activities of symmetrical bispyridinium and bisquinolinium compounds have been defined using quantitative structure-activity relationships (QSARs) and structural parameters. The design strategy followed in the development of the most active molecules is presented. The selective anticancer activity of these structures is also described. One promising anticancer compound has even entered clinical trials. Recently, ChoKα inhibitors have also been proposed as a novel therapeutic approach against parasites, rheumatoid arthritis, inflammatory processes, and pathogenic bacteria. The evidence for ChoKα as a novel drug target for approaches in precision medicine is discussed.
33618295 Anti-inflammatory effect of phenylpropanoids from Dendropanax dentiger in TNF-α-induced M 2021 May The root of Dendropanax dentiger (Harms) Merr. has been used for centuries as an empirical treatment for rheumatoid arthritis (RA) in China without scientific validation. In our recent study, nineteen phenylpropanoids (1-19) with cyclooxygenase-2 inhibitory activities from the ethanol extract of D. dentiger roots, indicated to have a potential anti-RA effect. This study, evaluated the anti-RA effect of 19 phenylpropanoids on tumor necrosis factor (TNF)-α induced inflammation in MH7A cells and clarified their underlying mechanisms. As a result, 16 compounds remarkably suppressed nitric oxide (NO) production at a concentration of 40 μM in TNF-α-induced MH7A cells. Among them, pinoresinol (12) and dendrocoumarin A (1) were the most effective substances, which showed significant inhibitory effect on NO production, with IC(50) values of 6.25 ± 0.42 and 7.87 ± 0.67 μM, respectively. Furthermore, pinoresinol and dendrocoumarin A remarkably decreased the levels of interleukin (IL)-2, 6, 8, and interferon-gamma (IFN-γ), as well as prominently reduced the phosphorylation protein levels of nuclear factor kappa B (NF-κB) p65, I-kappa-B-alpha (IkBα), protein kinase B (Akt), and c-Jun N-terminal kinase (JNK) by Western blot analysis. Taken together, our findings suggest that pinoresinol and dendrocoumarin A may offer new and safe anti-RA candidates by inhibiting NF-kB, Akt and JNK signaling pathways.
33146470 Impact of hydroxychloroquine on the gestational outcomes of pregnant women with immune sys 2021 Feb AIM: To evaluate the impact of hydroxychloroquine (HCQ) on the perinatal outcomes of pregnancies with immune system disorders that necessitate the use of the drug. METHODS: This cohort consisted of 202 pregnancies with poor obstetric history and immune system problems. Patients enrolled in special antenatal care program were administered low-dose low-molecular-weight heparin, low-dose salicylic acid and low-dose corticosteroid (prophylaxis protocol) as soon as their pregnancies were confirmed. Pregnancies with systemic lupus erythematosis, Sjogren syndrome and rheumatoid arthritis were additionally administered HCQ 200 mg daily as a part of their routine treatment. Pregnancies using HCQ were included in the study group (n = 39) while the remainders were included in control group (n = 163). We compared the groups in terms of the presence of miscarriage, fetal growth restriction (FGR), preeclampsia and preterm birth, as well as gestational week at birth, birthweight and "APGAR score of <7" at 10th minute. RESULTS: Miscarriage rates were 28.2% and 28.2% while preterm birth rates were 16.6% and 28.2% in the control and study groups, respectively (P = 0.215). Preeclampsia and HCQ-related side effects were not detected in the groups. There were also no significant differences between the groups in terms of FGR, gestational day at birth, birthweight and the presence of "APGAR score <7" at 10th minute (P = 0.462, P = 0.064, P = 0.273 and P = 0.627, respectively). CONCLUSION: Low-dose low-molecular-weight heparin, low-dose salicylic acid and low-dose corticosteroid prophylaxis together with HCQ seem to be promising in pregnancies with immune system disorders. HCQ seems to be a safe and effective drug in low dosages.
34854263 Journal Club Review of "What Is the Persistence to Methotrexate in Rheumatoid Arthritis, a 2022 Mar OBJECTIVE: The objectives of this study were to assess the 1-year persistence to methotrexate (MTX) initiated as the first ever conventional synthetic disease-modifying antirheumatic drug in new-onset rheumatoid arthritis (RA) and to investigate the marginal gains and robustness of the results by increasing the number and nature of covariates and by using data-driven, instead of hypothesis-based, methods to predict this persistence. METHODS: Through the Swedish Rheumatology Quality Register, linked to other data sources, we identified a cohort of 5475 patients with new-onset RA in 2006-2016 who were starting MTX monotherapy as their first disease-modifying antirheumatic drug. Data on phenotype at diagnosis and demographics were combined with increasingly detailed data on medical disease history and medication use in four increasingly complex data sets (48-4162 covariates). We performed manual model building using logistic regression. We also performed five different machine learning (ML) methods and combined the ML results into an ensemble model. We calculated the area under the receiver operating characteristic curve (AUROC) and made calibration plots. We trained on 90% of the data, and tested the models on a holdout data set. RESULTS: Of the 5475 patients, 3834 (70%) remained on MTX monotherapy 1 year after treatment start. Clinical RA disease activity and baseline characteristics were most strongly associated with the outcome. The best manual model had an AUROC of 0.66 (95% confidence interval [CI] 0.60-0.71). For the ML methods, Lasso regression performed best (AUROC = 0.67; 95% CI 0.62-0.71). CONCLUSION: Approximately two thirds of patients with early RA who start MTX remain on this therapy 1 year later. Predicting this persistence remains a challenge, whether using hypothesis-based or ML models, and may yet require additional types of data. https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/acr2.11266 Westerlind H, Maciejewski M, Frisell T, Jelinsky SA, Ziemek D, Askling J. What is the persistence to methotrexate in rheumatoid arthritis, and does machine learning outperform hypothesis-based approaches to its prediction? ACR Open Rheumatol 2021;3:457-463.
34576825 Gut Microbiota-Modulated Metabolomic Profiling Shapes the Etiology and Pathogenesis of Aut 2021 Sep 10 Autoimmunity is a complex and multifaceted process that contributes to widespread functional decline that affects multiple organs and tissues. The pandemic of autoimmune diseases, which are a global health concern, augments in both the prevalence and incidence of autoimmune diseases, including type 1 diabetes, multiple sclerosis, and rheumatoid arthritis. The development of autoimmune diseases is phenotypically associated with gut microbiota-modulated features at the molecular and cellular levels. The etiology and pathogenesis of autoimmune diseases comprise the alterations of immune systems with the innate and adaptive immune cell infiltration into specific organs and the augmented production of proinflammatory cytokines stimulated by commensal microbiota. However, the relative importance and mechanistic interrelationships between the gut microbial community and the immune system during progression of autoimmune diseases are still not well understood. In this review, we describe studies on the profiling of gut microbial signatures for the modulation of immunological homeostasis in multiple inflammatory diseases, elucidate their critical roles in the etiology and pathogenesis of autoimmune diseases, and discuss the implications of these findings for these disorders. Targeting intestinal microbiome and its metabolomic associations with the phenotype of autoimmunity will enable the progress of developing new therapeutic strategies to counteract microorganism-related immune dysfunction in these autoimmune diseases.
34498807 Evaluation of the potential drug interactions mediated through P-gp, OCT2, and MATE1/2K wi 2022 Feb Filgotinib, a preferential Janus Kinase-1 inhibitor, is approved in Europe and Japan for treatment of rheumatoid arthritis and is being developed for treatment of other chronic inflammatory diseases. Three drug-drug interactions studies were conducted in healthy subjects to evaluate the effect of P-glycoprotein (P-gp) modulation (study 1: P-gp inhibition by itraconazole and study 2: P-gp induction by rifampin) on filgotinib pharmacokinetics and the potential of filgotinib to impact exposure of metformin, an organic cation transporter (OCT) 2 and multidrug and toxin extrusion (MATE) 1/2K substrate (study 3). Co-administration of filgotinib with itraconazole increased filgotinib exposure (maximum concentration [C(max) ] by 64% and area under the curve to infinity [AUC(inf) ] by 45%) but had no effect on the exposure of GS-829845, filgotinib's primary metabolite. Rifampin moderately reduced exposures of filgotinib and GS-829845 (C(max) by 26% and AUC(inf) by 27% for filgotinib; C(max) by 19% and AUC(inf) by 38% for GS-829845). The data confirmed that filgotinib is a P-gp substrate. However, the magnitude of change in filgotinib/GS-829845 exposure by P-gp modulators is not deemed to be clinically relevant based on filgotinib exposure-response analyses in subjects with rheumatoid arthritis. Filgotinib did not alter metformin exposures, indicating that filgotinib and GS-829845 do not inhibit OCT2 and MATE1/2K at the clinical doses. Filgotinib was generally well-tolerated when administered alone or with the co-administered drugs in the studies. Results from these studies were the basis to enable the use of P-gp modulators and substrates of OCT2, MATE1, and MATE2K with filgotinib without the need for dose modifications in the current approved rheumatoid arthritis population.
34457039 Treatment approaches to patients with multiple sclerosis and coexisting autoimmune disorde 2021 The past decades have yielded major therapeutic advances in many autoimmune conditions - such as multiple sclerosis (MS) - and thus ushered in a new era of more targeted and increasingly potent immunotherapies. Yet this growing arsenal of therapeutic immune interventions has also rendered therapy much more challenging for the attending physician, especially when treating patients with more than one autoimmune condition. Importantly, some therapeutic strategies are either approved for several autoimmune disorders or may be repurposed for other conditions, therefore opening new curative possibilities in related fields. In this article, we especially focus on frequent and therapeutically relevant concomitant autoimmune conditions faced by neurologists when treating patients with MS, namely psoriasis, rheumatoid arthritis and inflammatory bowel diseases. We provide an overview of the available disease-modifying therapies, highlight possible contraindications, show pathophysiological overlaps and finally present which therapeutics can be utilized as a combinatory treatment, in order to 'kill two birds with one stone'.
34449533 Specificity of Anti-Citrullinated Protein Antibodies to Citrullinated α-Enolase Peptides 2021 Jul 21 Rheumatoid arthritis (RA) is an autoimmune disease affecting approximately 1-2% of the world population. In addition to the first discovered serologic markers for RA, the rheumatoid factors (RFs), anti-citrullinated protein antibodies (ACPAs) are even more specific for the disease compared to RFs and are found in 70-80% of RA patient sera. RA etiopathogenesis still needs to be elucidated, as different factors are proposed to be involved, such as Epstein-Barr virus infection. Hence, understanding the interaction between ACPAs and their citrullinated peptide targets is relevant for a better knowledge of RA pathophysiology and for diagnostic purposes. In this study, a cohort of RA sera, healthy control sera and multiple sclerosis sera were screened for reactivity to a variety of citrullinated peptides originating from α-enolase, pro-filaggrin, proteoglycan and Epstein-Barr nuclear antigen-2 by enzyme-linked immunosorbent assay. ACPA reactivity to citrullinated α-enolase peptides was found to depend on peptide length and peptide conformation, favouring cyclic (disulfide bond) conformations for long peptides and linear peptides for truncated ones. Additional investigations about the optimal peptide conformation for ACPA detection, employing pro-filaggrin and EBNA-2 peptides, confirmed these findings, indicating a positive effect of cyclization of longer peptides of approximately 20 amino acids. Moreover, screening of the citrullinated peptides confirmed that ACPAs can be divided into two groups based on their reactivity. Approximately 90% of RA sera recognize several peptide targets, being defined as cross-reactive or overlapping reactivities, and whose reactivity to the citrullinated peptide is considered primarily to be backbone-dependent. In contrast, approximately 10% recognize a single target and are defined as nonoverlapping, primarily depending on the specific amino acid side-chains in the epitope for a stable interaction. Collectively, this study contributed to characterize epitope composition and structure for optimal ACPA reactivity and to obtain further knowledge about the cross-reactive nature of ACPAs.
34453939 Low dose of quercetin-loaded pectin/casein microparticles reduces the oxidative stress in 2021 Nov 1 AIMS: Quercetin has been investigated as an agent to treat rheumatoid arthritis. At high doses it improves inflammation and the antioxidant status of arthritic rats, but it also exerts mitochondriotoxic and pro-oxidant activities. Beneficial effects of quercetin have not been found at low doses because of its chemical instability and low bioavailability. In the hope of overcoming these problems this study investigated the effects of long-term administration of quercetin-loaded pectin/casein microparticles on the oxidative status of liver and brain of rats with adjuvant-induced arthritis. MAIN METHODS: Particle morphology was viewed with transmission electron microscopy and the encapsulation efficiency was measured indirectly by X-ray diffraction. Quercetin microcapsules (10 mg/Kg) were orally administered to rats during 60 days. Inflammation indicators and oxidative stress markers were measured in addition to the respiratory activity and ROS production in isolated mitochondria. KEY FINDINGS: Quercetin was efficiently encapsulated inside the polymeric matrix, forming a solid amorphous solution. The administration of quercetin microparticles to arthritic rats almost normalized protein carbonylation, lipid peroxidation, the levels of reactive oxygen species as well as the reduced glutathione content in both liver and brain. The paw edema in arthritic rats was not responsive, but the plasmatic activity of ALT and the mitochondrial respiration were not affected by quercetin, indicating absence of mitochondriotoxic or hepatotoxic actions. SIGNIFICANCE: Quercetin-loaded pectin/casein microcapsules orally administered at a low dose improve oxidative stress of arthritic rats without a strong anti-inflammatory activity. This supports the long-term use of quercetin as an antioxidant agent to treat rheumatoid arthritis.
34560546 Integrated pharmacology reveals the mechanism of action of Bu-Shen-Tong-Du prescription ag 2021 Nov Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. Bu-Shen-Tong-Du prescription (BSP) has traditionally been used in to treat RA but its underlying mechanisms remain unclear. In this study, we explored the potential mechanisms of BSP in collagen-induced arthritis (CIA) rats, a classic animal model of RA. We employed an integrated pharmacology approach in combination with network pharmacology, (1)H-nuclear magnetic resonance (NMR) metabolomics, and biochemical analyses to determine the mechanisms of BSP for treating RA. We found that BSP can regulate immunity and inflammation by decreasing the spleen index; inhibiting hyperplasia of the white pulp; reducing the levels of IL-1β, IL-6, IL-17A, and IFN-γ; and increasing the levels of IL-10 in the serum. Network pharmacology was utilized to predict related signal transduction pathways of BSP in RA treatment. (1)H NMR metabolomics of the serum confirmed that BSP regulated energy metabolism and amino acid metabolism. Finally, we validated the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling pathway using immunohistochemical methods, which demonstrated that BSP controlled RA-induced inflammation by inhibiting the TLR4/NF-κB signaling pathway. These results confirm the therapeutic effect of BSP in a CIA rat model, which is exerted via the inhibition of the inflammation and the improvement of the immune function, balancing energy metabolism and amino acid metabolism, and inhibiting the TLR4/NF-κB signaling pathway. This study provides an experimental basis for using BSP as a combinatorial drug to inhibit inflammation and regulate immunity in the treatment of RA.
34885909 Investigating Antiarthritic Potential of Nanostructured Clove Oil (Syzygium aromaticum) in 2021 Dec 2 The combined application of clove oil in a lipid nanocarrier opens a promising avenue for bone and joints therapy. In this study, we successfully developed a tunable controlled-release lipid platform for the efficient delivery of clove oil (CO) for the treatment of rheumatoid arthritis (RA). The ultra-small nanostructured lipid carriers co-loaded with CO (CONCs) were developed through an aqueous titration method followed by microfluidization. The CONCs appeared to be spherical (particle size of 120 nm), stable (zeta potential of -27 mV), and entrapped efficiently (84.5%). In toluene:acetone:glacial acetic acid (90:9:1 percent v/v/v) solvent systems, high-performance thin layer chromatography (HPTLC) analysis revealed the primary components in CO as eugenol (R(F) = 0.58). The CONCs greatly increased the therapeutic impact of CO in both in vitro and in vivo biological tests, which was further supported by excellent antiarthritic action. The CONC had an antiarthritic activity that was slightly higher than neat CO and slightly lower than standard, according to our data. The improved formulation inhibited serum lysosomal enzymes and proinflammatory cytokines while also improving hind leg function. This study provides a proof of concept to treat RA with a new strategy utilizing essential oils via nanodelivery.
34283677 Sonographic findings of immunoglobulin G(4)-related sialadenitis and differences from Sjö 2022 Mar OBJECTIVE: To evaluate ultrasonic features of the major salivary glands in patients with immunoglobulin G(4)-related sialadenitis (IgG(4)-RS) and to explore the differences between IgG(4)-RS and Sjögren's syndrome (SS). METHOD: We conducted the study in 150 patients with IgG(4)-RS and 100 patients with SS. Ultrasonographic variables of the static images of major salivary glands were analysed. An experienced radiologist scored the confidence rating regarding the presence of the characteristic imaging findings using a five-grade rating system. Ultrasonography scores between IgG(4)-RS and SS were compared. RESULTS: The major salivary glands were significantly larger in patients with IgG(4)-RS than in the SS group. The main features of ultrasonography of the salivary glands in IgG(4)-RS were various hypoechoic lesions and increased colour Doppler signalling. In contrast, the major salivary glands in SS exhibited hyperechoic lines and/or spots and obscuration of the gland configuration. The scores of the summarized sonographic characteristics also showed statistically significant differences between the IgG(4)-RS and SS groups. CONCLUSION: This study revealed different ultrasonic features of the major salivary glands in patients with IgG(4)-RS and SS. The scored sonographic features were helpful in differentiating IgG(4)-RS from SS. Consequently, we suggest that ultrasonography of major salivary glands could be a useful imaging procedure in the evaluation of patients suspected of having IgG(4)-RS.
33958361 Hypokalaemic paralysis as the initial clinical presentation of Sjogren's syndrome induced 2021 May 6 A 41-year-old woman presented by ambulance with a 1-day history of new-onset paralysis and nausea and vomiting ongoing for 48 hours. She had no history of any similar episodes. Biochemical analysis showed profound hypokalaemia with a non-anion gap metabolic acidosis. Her initial serum chloride was within the normal range. She had significant electrocardiographic changes on admission with ST depression, U waves and a prolonged QT interval. Urinary anion gap supported the diagnosis of a distal renal tubular acidosis. Subsequent connective tissue disease serology confirmed previously undiagnosed Sjogren's syndrome. Successful recovery for this patient required multidisciplinary input from the intensive care, nephrology and neurology teams.
34215328 Sjögren's syndrome in children: about 15 cases in Guinea Conakry. 2021 Jul 2 OBJECTIVES: Sjögren's syndrome is rare in children and most often secondary. It frequently affects girls and is characterized by dry eye syndrome, mouth and sometimes systemic involvement. Its diagnosis is difficult to establish in children. We report a series of 15 cases of Sjögren's syndrome in order to clarify the peculiarities of this condition in children. PATIENTS AND METHODS: This retrospective study was carried out over a 2-year period focused on children under 16 years of age who had been followed for Sjögren's syndrome in the rheumatology and pediatric departments. Patient data were collected and then analyzed by STATA/SE version 11.2 software. Anonymity and respect for ethical rules were the norm. There was no connection between the patients and the researchers. DESCRIPTION OF CASES: The mean age of the patients was 11 years with extremes of 5-15 years. History reveals that a dry mouth was found in more than half of the cases, or in 10 (66.7%) patients. Clinical examination found oral ulceration and periodontitis in equal proportions, 6 (40%). The immunological workup and the biopsy of the accessory salivary glands served as diagnostic evidence in the 15 patients according to the US-European criteria of 2002. CONCLUSION: Sjögren's syndrome is a rare entity in pediatrics. Its diagnosis is difficult to establish in pediatrics and its severity is linked to the occurrence of late visceral and lymphomatous sicca syndrome. Rapid diagnosis and initiation of a synthetic antimalarial (hydroxychloroquine) increases the hope of a cure.
33588937 Increase of aerobic glycolysis mediated by activated T helper cells drives synovial fibrob 2021 Feb 15 BACKGROUND: A dysregulated glucose metabolism in synovial fibroblasts (SF) has been associated with their aggressive phenotype in rheumatoid arthritis (RA). Even though T helper (Th) cells are key effector cells in the propagation and exacerbation of synovitis in RA, little is known about their influence on the metabolism of SF. Thus, this study investigates the effect of Th cells on the glucose metabolism and phenotype of SF and how this is influenced by the blockade of cytokines, janus kinases (JAKs) and glycolysis. METHODS: SF from patients with RA or osteoarthritis (OA) were cultured in the presence of a stable glucose isotopomer ([U-(13)C]-glucose) and stimulated with the conditioned media of activated Th cells (ThCM). Glucose consumption and lactate production were measured by proton nuclear magnetic resonance ((1)H NMR) spectroscopy. Cytokine secretion was quantified by ELISA. The expression of glycolytic enzymes was analysed by PCR, western blot and immunofluorescence. JAKs were blocked using either baricitinib or tofacitinib and glycolysis by using either 3-bromopyruvate or FX11. RESULTS: Quiescent RASF produced significantly higher levels of lactate, interleukin (IL)-6 and matrix metalloproteinase (MMP) 3 than OASF. Stimulation by ThCM clearly changed the metabolic profile of both RASF and OASF by inducing a shift towards aerobic glycolysis with strongly increased lactate production together with a rise in IL-6 and MMP3 secretion. Interestingly, chronic stimulation of OASF by ThCM triggered an inflammatory phenotype with significantly increased glycolytic activity compared to unstimulated, singly stimulated or re-stimulated OASF. Finally, in contrast to cytokine-neutralizing biologics, inhibition of JAKs or glycolytic enzymes both significantly reduced lactate production and cytokine secretion by Th cell-stimulated SF. CONCLUSIONS: Soluble mediators released by Th cells drive SF towards a glycolytic and pro-inflammatory phenotype. Targeting of JAKs or glycolytic enzymes both potently modulate SF's glucose metabolism and decrease the release of IL-6 and MMP3. Thus, manipulation of glycolytic pathways could represent a new therapeutic strategy to decrease the pro-inflammatory phenotype of SF.
34605719 CD4(+) T-cell DNA methylation changes during pregnancy significantly correlate with diseas 2021 Oct 4 Epigenetics may play a central, yet unexplored, role in the profound changes that the maternal immune system undergoes during pregnancy and could be involved in the pregnancy-induced modulation of several autoimmune diseases. We investigated changes in the methylome in isolated circulating CD4(+) T-cells in non-pregnant and pregnant women, during the 1(st) and 2(nd) trimester, using the Illumina Infinium Human Methylation 450K array, and explored how these changes were related to autoimmune diseases that are known to be affected during pregnancy. Pregnancy was associated with several hundreds of methylation differences, particularly during the 2(nd) trimester. A network-based modular approach identified several genes, e.g., CD28, FYN, VAV1 and pathways related to T-cell signalling and activation, highlighting T-cell regulation as a central component of the observed methylation alterations. The identified pregnancy module was significantly enriched for disease-associated methylation changes related to multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. A negative correlation between pregnancy-associated methylation changes and disease-associated changes was found for multiple sclerosis and rheumatoid arthritis, diseases that are known to improve during pregnancy whereas a positive correlation was found for systemic lupus erythematosus, a disease that instead worsens during pregnancy. Thus, the directionality of the observed changes is in line with the previously observed effect of pregnancy on disease activity. Our systems medicine approach supports the importance of the methylome in immune regulation of T-cells during pregnancy. Our findings highlight the relevance of using pregnancy as a model for understanding and identifying disease-related mechanisms involved in the modulation of autoimmune diseases.Abbreviations: BMIQ: beta-mixture quantile dilation; DMGs: differentially methylated genes; DMPs: differentially methylated probes; FE: fold enrichment; FDR: false discovery rate; GO: gene ontology; GWAS: genome-wide association studies; MDS: multidimensional scaling; MS: multiple sclerosis; PBMC: peripheral blood mononuclear cells; PBS: phosphate buffered saline; PPI; protein-protein interaction; RA: rheumatoid arthritis; SD: standard deviation; SLE: systemic lupus erythematosus; SNP: single nucleotide polymorphism; T(H): CD4(+) T helper cell; VIStA: diVIsive Shuffling Approach.
34962116 Adult-onset Still's Disease after BNT162b2 mRNA COVID-19 Vaccine. 2021 Dec 27 The coronavirus disease 2019 (COVID-19) pandemic is being overcome by widespread inoculation with various COVID-19 vaccines, but concerns about the safety of the vaccines are a major hurdle to widespread vaccination. We report the first case of adult-onset Still's disease (AOSD) developing in a 36-year-old, previously healthy woman after the first dose of BNT162b2 mRNA COVID-19 vaccine (Pfizer). She visited our hospital due to high spiking fever and sore throat that developed 10 days after vaccination. Based on thorough investigations and changes in symptoms and signs after admission, she was diagnosed with AOSD and treated with high dose steroids and tocilizumab. This report suggests the possibility that AOSD could be triggered by COVID-19 vaccines through activation of the innate immune system.
33264685 Cicatrizing conjunctivitis as an uncommon manifestation of primary Sjögren's syndrome. 2021 Jan PURPOSE: To report occurrence of cicatrizing conjunctivitis as an extraglandular ocular manifestation of primary Sjögren's syndrome (SS). METHODS: Medical charts of all patients with SS evaluated at two tertiary ophthalmological referral centers were reviewed. Patients who demonstrated clinical findings of cicatrizing conjunctivitis were included in this review. Patient and disease-related data including ocular complications, therapies and outcomes were collected. RESULTS: Eight patients with a diagnosisis of SS were noted to have cicatrizing conjunctivitis findings over a period of 11 years (between 2009 and 2020). Mean age of patients was 79. All patients had a negative immunoreactant deposition in conjunctival biopsy. Mean follow-up time was 6 years (range, 18-197 months). Three patients had progression of conjunctival scarring. Worsening of vision occurred in 4 patients due to corneal complications, including ulceration, perforation and scarring. CONCLUSIONS: SS is an under-recognized etiology of severe progressive cicatrizing conjunctivitis that can lead to ocular morbidity and loss of vision without appropriate management.
33070375 Cytokine profiles and clinical characteristics in primary Sjögren´s syndrome patient gro 2021 Feb BACKGROUND: Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by a lymphocytic infiltrate in salivary glands driving to epithelial damage. The pSS patients present heterogenic clinical and serological characteristics. This heterogenicity could be due to the cytokine microenvironment. Cytokine levels have been analyzed and reported individually, showing controversial results; for that reason, we considered essential to evaluate a cluster of cytokines and relate them with antibody levels and clinical characteristics to find pSS subgroups. METHODS: Ninety-nine pSS patients, diagnosed by the 2016 ACR/EULAR classification criteria, and 76 control subjects (CS) were included. Cytokine quantification was performed by Multiplex assay. Principal component analysis (PCA) was realized, and the K-mean test was used to identify clusters/groups. Groups were analyzed by the Kruskal-Wallis test and the Bonferroni test. RESULTS: Higher IFN-γ, IL-17F, IL-21, IL-23, IL-4, and IL-31 levels were observed in pSS patients in comparison with control subjects. PCA analysis showed three groups. The severe group was characterized by higher cytokine concentrations as well as an increase in clinical parameters such as antibody levels, damage index score, and others. The moderate group presented intermediate severity; meanwhile, the mild group presented the lowest severity. CONCLUSION: Cluster analysis revealed three groups that were different in cytokine levels and clinical parameters in which the mild group was defined by lower severity, the moderate group with intermediate severity, and the severe group with higher severity. This analysis could help subclassify the primary Sjögren syndrome patients for a better understanding of the clinical phenotype that impacts the treatment approach.
33055548 A New Screening Questionnaire to Identify Patients With Dry Eye With a High Likelihood of 2021 Feb 1 PURPOSE: To develop a screening questionnaire to identify patients with dry eye with a high likelihood of having underlying Sjögren syndrome (SS). METHODS: This was a cross-sectional study of participants with dry eye complaints who were self-referred or referred by an ophthalmologist to the Sjögren's International Collaborative Clinical Alliance study. Symptoms and ocular surface examination findings were candidate predictors. Univariable and multivariable logistic regression analyses were performed to estimate odds ratios (ORs) and 95% confidence intervals (95% CI) for the association of a symptom and/or ocular sign with SS. Area under the receiver operating characteristic curve (AUC) was used to summarize the predictive ability of different regression models and the derived likelihood score. RESULTS: Four questions were statistically significant in the final multivariable model: 1) Is your mouth dry when eating a meal? [Yes = OR 1.63 (1.18-2.26)]; 2) Can you eat a cracker without drinking a fluid or liquid? [No = OR 1.46 (1.06-2.01)]; 3) How often do you have excessive tearing? [None of the time = OR 4.06 (1.81-9.10)]; and 4) Are you able to produce tears? [No = OR 2.24 (1.62-3.09)]. The SS likelihood score had an AUC of 0.70 (95% CI, 0.66-0.73), and when including tear break-up time and conjunctival staining, it yielded an AUC of 0.79 (95% CI, 0.77-0.82). CONCLUSIONS: This questionnaire can be used to identify patients with dry eye with a high likelihood of having SS. With future refinement and validation, this screening tool could be used alone or in combination with examination findings to identify patients with SS earlier, thereby facilitating better clinical outcomes.