Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
35411013 Anti-HMGB1 antibody is a potential characteristic autoantibody for Sjögren's syndrome. 2022 Apr 11 Sjögren's syndrome (SS) is a common chronic inflammatory autoimmune disease that affects about 0.33-0.77% population in China. The positive for antinuclear antibodies (ANA) is one of the key features of SS, which shows a nuclear fine speckled (AC-4) pattern in an indirect immunofluorescent antibody test (IIFT). About 70% of ANA-positive SS patients have detectable anti-SS-A and/or SS-B antibodies, which indicates that other autoantibodies may present in SS patients. The anti-HMGB1 antibodies in 93 SS patients and 96 healthy controls were investigated with in-house developed ELISA and immunoblotting, and the locations of HMGB1 and fluorescent pattern of anti-HMGB1 antibody were investigated with IIFT. The contribution of anti-HMGB1 antibody in ANA-IF was evaluated with Cas9-induce HMGB1 knockout B16 cells. The anti-HMGB1 antibody level is higher in SS patients (9.96 ± 5.55 RU/ml) than in healthy controls (4.9 ± 1.4 RU/ml). With ROC curve analysis, when taking 8 RU/ml as the cutoff value, the sensitivity, specificity, and the area under the curve were 64.5%, 96.9%, and 0.83, respectively. A total of 18 patients (20.7%) with nuclear fine speckled (AC-4) pattern in ANA-IF test were anti-HMGB1 antibody positive only. With commercial antibody, anti-HMGB1 antibody showed the same nuclear fine speckled (AC-4) pattern. The serum from ANA-IF (+), SS-A (-), and SS-B (-) SS patients showed nuclear fine speckled (AC-4) pattern in wildtype B16 cells, but no fluorescence in HMGB1 knockout B16 cells. Anti-HMGB1 antibody may be one of the characteristic autoantibodies of SS in addition to anti-SS-A and SS-B. The detection of anti-HMGB1 antibody can provide more laboratory evidence for clinical diagnosis of SS.
33432638 Gluten-free diet modulates inflammation in salivary glands and pancreatic islets. 2022 Apr OBJECTIVES: A lifelong gluten-free (GF) diet ameliorates autoimmune diabetes in non-obese diabetic (NOD) mice and most likely in humans. Besides diabetes, NOD mice develop focal sialadenitis, as seen in Sjögren's syndrome (SS). In humans, type 1 diabetes (T1D) is also linked to SS. Here, we investigated whether a lifelong GF diet influences the immune cell infiltration in the salivary glands and pancreatic islets in NOD mice. METHODS: NOD mice were fed a lifelong (i.e. 13 weeks) GF or gluten-containing standard (STD) diet. Insulitis and sialadenitis were scored on H&E-stained paraffin-embedded sections of pancreas and submandibular glands. Immune cell specificity and distribution were investigated immunohistochemically. RESULTS: There were fewer CD68+ and CD4+ cells in submandibular gland areas with focal sialadenitis as well as reduced insulitis and fewer VEGFR2+ cells in pancreatic islets in mice on GF versus STD diet. The degree of sialadenitis was not significantly lower in GF mice, but sialadenitis and insulitis correlated strongly. Lung weight was lower in GF mice. CONCLUSION: In NOD mice, a lifelong GF diet reduces infiltration of monocytes/macrophages and T cells in salivary glands and inflammation in pancreatic islets, possibly by reducing VEGFR2, indicating that the linked autoimmune diseases, T1D and SS, may be alleviated by a GF diet.
34894252 Interluekin-6 inhibitors for the treatment of adult-onset Still's disease. 2022 Jan 5 Adult-onset Still's disease is a systemic inflammatory disease characterized by high spiking fever, arthritis, evanescent skin rash, leukocytosis, and hyperferritinemia. The pathogenesis of adult-onset Still's disease has not been fully understood yet; however, multiple proinflammatory cytokines, such as IL-1β and IL-6, play important roles in the development of adult-onset Still's disease. IL-6 is a multifunctional cytokine that accelerates the differentiation of macrophages and cytotoxic T-cells and chemotaxis of neutrophils and macrophages. Serum concentrations of IL-6 well correlate with disease activity of adult-onset Still's disease, and blockade of IL-6 has been proven to be effective in active adult-onset Still's disease. This review will focus on the recent understanding of the role of proinflammatory cytokines of adult-onset Still's disease and the efficacy of IL-6 inhibitors for the treatment of adult-onset Still's disease.
33998362 A novel diagnostic technique of measuring labial minor salivary gland secretions using sod 2022 Jan 2 PURPOSE: To evaluate the lower labial minor salivary glands (MSGs) flow rate using fluorescein dye in healthy individuals and patients with Sjögren's syndrome (SS) and Stevens-Johnson syndrome (SJS). METHODS: Thirty consecutive patients with SS (N = 15; mean age 35.7 years) and SJS (N = 15; 57.7 years), and their age- and sex-matched healthy controls (N = 40; mean ocular surface disease index (OSDI) = 6.1) had ocular examination and whole lower labial mucosa evaluation after ophthalmic fluorescein strip application under cobalt blue light. Analyzed parameters include average labial distribution of functional MSGs, their secretory flow rate, and comparison between healthy and diseased groups. RESULTS: The mean salivary flow rate from the lower labial MSGs of normal individuals showed decade-wise decline (2.7 ± 0.29 μl/min, 2.6 ± 0.39 μl/min, 2.3 ± 0.6 μl/min, 1.9 ± 0.95 μl/min) with similar trend for the number of secreting MSG openings (38.7, 37.2, 30, 22). The mean OSDI score was 45.3 in SJS and 28.2 in SS group. Thirty eyes in each SS and SJS group had mean Schirmer I value of 1.5 ± 2.2 mm and 5.1 ± 4.4 mm. The mean lower labial salivary flow rate in SS group was 0.5 ± 0.28 μl/min, and 2.0 ± 0.95 μl/min in SJS group. When compared to normal, SS patients had a significant reduction in the flow rate (p < .00001); however, it was not significant for the SJS group (p = .28). The mean number of secreting MSG openings was reduced in both the groups compared to normal (SJS, 20.5; p = .01 and SS, 12; p < .0001). There was a significant difference between SS and SJS groups in terms of flow rate (p < .00001) and number of MSG openings (p = .001). The MSG flow rate and Schirmer values did not show any correlation in SS or SJS patients. CONCLUSION: The fluorescein-assisted evaluation of the lower lip can be used as a quantitative method for measuring the labial salivary flow rate in SS and SJS patients.
35362033 Pediatric Trigger Digits. 2022 Apr 1 Pediatric trigger thumb (PTT) and finger (PTF) are upper extremity deformities that frequently go unrecognized by providers. Early recognition by pediatricians and caregivers is vital because PTT is successfully treated nonoperatively in more than 95% of patients if diagnosed early. Similarly, PTF can be successfully treated nonoperatively in 67% of patients. Although PTT is typically benign and 10 times more common, PTF may be associated with underlying concurrent medical conditions, such as juvenile rheumatoid arthritis, diabetes, mucopolysaccharide and lysosomal disorders, and trisomy 18. Routine examinations consisting of full hand range of motion should be performed in all children. Clinicians should be aware of the importance of conservative treatment options for PTT and PTF and the value of screening for underlying medical conditions associated with PTF.
35453416 Sp1 S-Sulfhydration Induced by Hydrogen Sulfide Inhibits Inflammation via HDAC6/MyD88/NF-Π2022 Apr 7 Histone deacetylase 6 (HDAC6) acts as a regulator of the nuclear factor kappa-B (NF-κB) signaling pathway by deacetylating the non-histone protein myeloid differentiation primary response 88 (MyD88) at lysine residues, which is an adapter protein for the Toll-like receptor (TLR) and interleukin (IL)-1β receptor. Over-activated immune responses, induced by infiltrated immune cells, excessively trigger the NF-κB signaling pathway in other effector cells and contribute to the development of rheumatoid arthritis (RA). It has also been reported that HDAC6 can promote the activation of the NF-κB signaling pathway. In the present study, we showed that HDAC6 protein level was increased in the synovium tissues of adjuvant-induced arthritis rats. In addition, hydrogen sulfide (H(2)S) donor S-propargyl-cysteine (SPRC) can inhibit HDAC6 expression and alleviate inflammatory response in vivo. In vitro study revealed that HDAC6 overexpression activated the NF-κB signaling pathway by deacetylating MyD88. Meanwhile, sodium hydrosulfide (NaHS) or HDAC6 inhibitor tubastatin A (tubA) suppressed the pro-inflammatory function of HDAC6. Furthermore, the reduced expression of HDAC6 appeared to result from transcriptional inhibition by S-sulfhydrating specificity protein 1 (Sp1), which is a transcription factor of HDAC6. Our results demonstrate that Sp1 can regulate HDAC6 expression, and S-sulfhydration of Sp1 by antioxidant molecular H(2)S ameliorates RA progression via the HDAC6/MyD88/NF-κB signaling pathway.
30860699 Anatomy, Shoulder and Upper Limb, Metacarpophalangeal Joints. 2022 Jan The metacarpophalangeal (MCP) joints are diarthrodial joints where the large convex heads of the distal aspect of the metacarpals articulate with the concave-shaped proximal aspect of each phalange. The articulating surface of each metacarpal head and proximal phalange is composed of hyaline cartilage. There are five separate MCP joints in each hand and these joints serve as transitions between the palm and the fingers. In layman's terms, the MCP joints are known as the “knuckles,” and the metacarpal heads are especially prominent dorsally when making a fist. These joints provide a combination of stability and flexibility which allows for the dexterity required by the hand. Similar to other joints in the body, the MCP joints are acted upon by muscles to allow for specific joint movements. These movements include flexion, extension, abduction, adduction, and limited circumduction. Clinically, arthritis involving the MCP joints is a classic and differentiating feature of rheumatoid arthritis (RA) from osteoarthritis (OA), which typically involves the distal interphalangeal (DIP) joints.
28613703 Sjogren Syndrome. 2022 Jan In the early 1900s, Swedish physician Henrik Sjögren (SHOW-gren) first described a group of women whose chronic arthritis was accompanied by dry eyes and dry mouth. Today, Rheumatologists know more about the syndrome that is named for Sjögren and—most significantly for patients—can offer advice about how to live with it. Primary Sjogren syndrome is a systemic autoimmune disorder most commonly presenting with sicca symptoms. Sicca refers to dryness most often involving the eyes and mouth due to inflammation and resultant pathology of the lacrimal and salivary glands. Up to one-half of affected individuals also develop extra-glandular involvement implying the occurrence of signs and symptoms in organs distinct from the salivary and lacrimal glands including the joints, skin, lungs, gastrointestinal (GI) tract, nervous system, and kidneys. Sjogren syndrome frequently occurs in conjunction with other autoimmune disorders including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In this setting, authors will refer to it as secondary Sjogren or Sjogren-overlap syndrome. Therapies are directed toward replacing moisture at affected glandular sites and suppressing the autoimmune response locally as well as systemically.
35452005 Bone Scan With SPECT/CT Demonstrated C1 to C2 Involvement in Rheumatic Arthritis. 2022 Apr 22 An 80-year-old man was treated with rituximab for active rheumatoid arthritis until 2019, now controlled with Salazopyrin, prednisolone, methotrexate, and folic acid. However, laboratory data showed elevated C-reactive protein and erythrocyte sedimentation rate. Whole-body bone scan showed bony and joint destruction to the upper cervical vertebra (C spine), bilateral shoulders, wrists, finger joints, ankles, and left knee. SPECT/CT localized the upper C spine uptake to the C1/C2 joint and adjacent C1 and C2 with C1/C2 subluxation. C spine CT showed vertical atlantoaxial subluxation and bony erosions.
32965154 Diagnostic and Prognostic Roles of Serum Interleukin-6 Levels in Patients with Uveitis. 2022 Feb 17 PURPOSE: To examine the diagnostic and prognostic roles of serum interleukin-6 levels in patients with uveitis. METHODS: This was a retrospective observational case series. Demographic and clinical characteristics were compared between Group One (sixty patients) with normal serum IL-6 levels and Group Two (twenty patients) with high serum interleukin-6 levels. RESULTS: Mean IL-6 level was 1.77 ± 0.97 pg/ml and 10.2 ± 9.7 pg/ml in Group One and Group Two respectively. Age, presence of systemic disease, and mean number of flare-ups were statistically significant (p = .015, p = .000, p = .03, respectively). Multivariate analysis was performed on variables that were statistically significant in univariate analysis and showed that three variables had significant correlation with IL-6 levels in both groups: systemic disease (OR = 10.83, p < .001), Age (OR = 0.95, p = .03) and number of flare-ups (OR = 2.9, p = .02). CONCLUSION: Serum IL-6 levels can provide diagnostic and prognostic information in regard to the course of disease and its treatment.
32009458 Unplanned Reoperation and Implant Revision After Total Wrist Arthroplasty. 2022 Jan Background: Total wrist arthroplasty (TWA) is a treatment option for many debilitating wrist conditions. With recent improvements in implant design, indications for TWA have broadened. However, despite these improvements, there are still complications associated with TWA, such as unplanned reoperation and eventual implant removal. The goal of this study was to identify risk factors for an unplanned reoperation or implant revision after a TWA at 2 academic medical centers between 2002 and 2015. Methods: In this retrospective study, 24 consecutive TWAs were identified using CPT codes. Medical records were manually reviewed to identify demographic, patient- or disease-related, and surgery-related risk factors for reoperation and implant removal after a primary TWA. Results: Forty-six percent of wrists (11 of 24 TWAs performed) had a reoperation after a median of 3.4 years, while 29% (7 of 24) underwent implant revision after a median of 5 years. Two patients had wrist surgery prior to their TWA, both eventually had their implant removed (P = .08). There were no risk factors associated with reoperation or implant removal. Conclusion: Unplanned reoperation and implant removal after a primary TWA are common. Approximately 1 in 3 wrists are likely to undergo revision surgery. We found no factors associated with reoperation or implant removal; however, prior wrist surgery showed a trend toward risk of implant removal after TWA.
35511905 Sex difference in disease burden of inflammatory arthritis patients treated with tumor nec 2022 OBJECTIVE: Knowledge is needed on the total disease burden across the sexes in inflammatory arthritis (IA). We aimed to compare disease burden, including a broad range of health aspects, across men and women with IA treated with tumor necrosis factor inhibitors (TNFi). METHODS: Adult outpatients with IA (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis) were included as part of standard care. Patient-reported outcomes, disease activity, TNFi trough levels, calprotectin, Work Productivity and Activity Impairment, comorbidities and cardiovascular risk profile were assessed. Unadjusted comparisons across sexes were done with independent t-test, Mann-Whitney U-test and X2-test and adjusted analyses with General Linear Models and logistic/ordinal logistic regression. RESULTS: A total of 305 IA patients were included (167 men, 138 women). A significantly lower proportion of women (45%) than men (59%) were in remission according to disease-specific composite scores (p = 0.02). Women had significantly worse scores on pain, joint pain, fatigue, enthesitis, Health Assessment Questionnaire and Short Form (SF)-36 vitality and social functioning (all p≤0.04). Both sexes had worse SF-36 scale scores than the general population. Women reported more absenteeism (work time missed) and activity impairment. TNFi trough levels, neutralizing antibodies and calprotectin were similar across sexes. A similar total number of comorbidities was seen. Self-reported hypothyroidism was more frequent in women. Men had higher 10-year calculated risk of fatal cardiovascular events. CONCLUSION: Important differences in disease burden between men and women were seen. More attention to sex differences in the follow-up of IA patients is warranted.
35084325 Enhanced expression of mRNA for transforming growth factor β activated kinase 1 in CD34+ 2022 Jan 27 OBJECTIVES: Transforming growth factor β activated kinase 1 (TAK1) has been found to mediate maladaptive tumour necrosis factor (TNF) signalling, leading to hyperactive downstream nuclear factor Kappa β (NF-κB) signalling. We explored the expression of TAK1 mRNA in bone marrow CD34+ cells in rheumatoid arthritis (RA) to delineate the mechanism for their abnormal response to TNF-α and differentiate into fibroblast-like cells. METHODS: CD34+ cells were purified from bone marrow samples obtained from 47 RA patients and 27 osteoarthritis (OA) patients during joint operations via aspiration from the iliac crest. The expression of mRNAs for TAK1 and NFκB1 was examined by quantitative RT-PCR. RESULTS: TAK1 mRNA expression in bone marrow CD34+ cells was significantly higher in RA than in OA (TAK1/β-actin: [11.980 ± 2.380] x 10-3 and [5.593±1.307] x 10-3 [mean ± SEM], respectively; p=0.0238). TAk1 mRNA expression was not different depending on the type of operated joints or on the severity type of RA. Nor was it correlated with serum CRP or rheumatoid factor or with administration of methotrexate, other conventional synthetic disease-modifying anti-rheumatic drugs or oral glucocorticoid. TAK1 mRNA expression was significantly correlated with NFκB1 mRNA expression in RA bone marrow CD34+ cells. CONCLUSIONS: These results indicate that TAK1 mRNA expression is enhanced in bone marrow CD34+ cells independently of the clinimetrics or treatment in RA. It is also suggested that the upregulation of TAK1 mRNA expression might lead to the enhanced expression of NFκB1 mRNA in bone marrow CD34+ cells, but possibly not vice versa, resulting in their abnormal response to TNF-α.
35330335 Adalimumab and ABP 501 in the Treatment of a Large Cohort of Patients with Inflammatory Ar 2022 Feb 23 The recent introduction of ABP 501, an adalimumab biosimilar, in the treatment of rheumatic diseases was supported by a comprehensive comparability exercise with its originator. On the other hand, observational studies comparing adalimumab and ABP 501 in inflammatory arthritis are still lacking. The main aim of this study is to compare the clinical outcomes of the treatment with adalimumab, both the originator and ABP 501, in a large cohort of patients affected by autoimmune arthritis in a real life setting. We retrospectively analysed the baseline characteristics and the retention rate in a cohort of patients who received at least a course of adalimumab (originator or ABP 501) from January 2003 to December 2020. We stratified the study population according to adalimumab use: naive to original (oADA), naive to ABP 501 (bADA) and switched from original to ABP 501 (sADA). The oADA, bADA and sADA groups included, respectively, 724, 129 and 193 patients. In each group, the majority of patients had a diagnosis of rheumatoid arthritis. The total observation period was 9805.6 patient-months. The 18-month retentions rate in oADA, bADA and sADA was, respectively, 81.5%, 84.0% and 88.0% (p > 0.05). The factors influencing the adalimumab retention rate were an axial spondylarthritis diagnosis (Hazard Ratio (HR) 0.70; p = 0.04), switch from oADA to ABP 501 (HR 0.53; p = 0.02) and year of prescription (HR 1.04; p = 0.04). In this retrospective study, patients naive to the adalimumab originator and its biosimilar ABP 501 showed the same retention rate. Patients switching from the originator to biosimilar had a higher retention rate, even though not statistically significant, when compared to naive.
33760442 Shrinking Lung Syndrome. 2022 Jan Shrinking lung syndrome (SLS) is a rare complication of systemic autoimmune disease. It occurs most commonly in systemic lupus erythematosus but there are rare reports of it developing in systemic sclerosis, Sjogren's syndrome, and rheumatoid arthritis. It should be suspected in a patient with a relevant autoimmune disease who presents with exertional shortness of breath with or without pleuritic chest pain with radiographic evidence of unilateral or bilateral elevation of the hemidiaphragm or diaphragms. Reduced lung volumes and a restrictive deficit on lung function testing are typical. It is a diagnosis of exclusion and therefore other investigations such as computed tomography of the chest are undertaken to exclude competing diagnoses.
31855356 Chloroquine. 2022 Jan Chloroquine is a medication used in the management and treatment of malaria and inflammatory diseases. It is in the sulfonamides class of drugs. This activity describes the indications, action, and contraindications for chloroquine as a valuable agent in the therapy of malaria, rheumatoid arthritis, and lupus erythematosus. This activity will highlight the mechanism of action, adverse event profile, and other key factors (e.g., off-label uses, dosing, pharmacodynamics, pharmacokinetics, monitoring, relevant interactions) pertinent for members of the interprofessional team in the treatment, prevention, and management of patients with malaria and related conditions.
29939640 Disease Modifying Anti-Rheumatic Drugs (DMARD). 2022 Jan Disease-modifying antirheumatic drugs (DMARDs) are a class of drugs indicated for the treatment of several inflammatory arthritides, including rheumatoid arthritis (RA), as well as for the management of other connective tissue diseases and some cancers. This activity will highlight the mechanism of action, adverse event profile, pharmacology, monitoring, and relevant interactions of DMARDs, pertinent for members of the interprofessional team in the treatment of patients with autoimmune disorders that will respond to such therapy.
30570980 Celecoxib. 2022 Jan The FDA recommends celecoxib and other NSAIDs (non-steroidal anti-inflammatory drugs), along with acetaminophen, as first-line analgesics for patients with osteoarthritis and rheumatoid arthritis. Celecoxib also has an FDA indication for the management of acute pain in adult women and primary dysmenorrhea. Furthermore, the FDA also recommends using celecoxib as an adjunct therapy in patients with familial adenomatous polyposis to reduce the number of colorectal polyps. This activity reviews the mechanism of action, adverse event profile, toxicity, dosing, pharmacodynamics, and monitoring of celecoxib, pertinent for clinicians and other interprofessional team members to allow for appropriate utilization of celecoxib.
31194347 Azathioprine. 2022 Jan Azathioprine (AZA) is a medication used in the management and treatment of active rheumatoid arthritis (RA) and the prevention of kidney transplant rejection. This activity reviews the indications, action, and contraindications for azathioprine as a valuable agent in treating RA and other disorders when applicable. This activity will highlight the mechanism of action, adverse event profile, and other key factors (e.g., off-label uses, dosing, pharmacodynamics, pharmacokinetics, monitoring, relevant interactions) pertinent for members of the interprofessional team in the treatment of patients with RA and related conditions.
35582851 Structure of type II collagen from sturgeon cartilage and its effect on adjuvant-induced r 2022 May 18 The purpose of this paper was to extract and characterize type II collagen of sturgeon cartilage (SC-CII), and to explore the effects of taking SC-CII orally on rheumatoid arthritis (RA) in rats. SC-CII showed a triple-helix structure (RPN = 0.12), with d1 of 11.82 Å and d2 of 4.08 Å, which was analyzed by FT-IR, CD, XRD, and MS. It was constructed of the repeating tripeptide unit Gly-X-Y, where X and Y are generally Pro or Hyp, proved by amino acid composition and peptide mass fingerprinting. Furthermore, the effects of SC-CII on RA were evaluated. Ankle thickness was significantly decreased in SC-CII groups, with changes in lymphocyte proliferation also observed. Compared with the model control group, there was an evident decrease in TNF-α, IL-1β, COX-2, MCP-1, and TLR-4 mRNA levels, but no remarkable differences in APF, MMP-3, and MyD88 mRNA levels in the SC-CII groups. In addition, TNF-α, IL-1β, RF, Anti-CII Ab were significantly reduced in the SC-CII groups, proved by ELISA. Therefore, SC-CII showed alleviating effects on RA through the TLR4/MyD88-NFκB pathway.