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35377442 All-cause and cause-specific mortality in rheumatoid arthritis, psoriatic arthritis and ax 2022 Apr 4 OBJECTIVES: To explore mortality and causes of death among Norwegian patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) compared with the general population by conducting a nationwide registry-based cohort study. METHODS: Patients with RA, PsA and axSpA were identified from the Norwegian Patient Registry based on ICD-10-codes between 2008 and 2017. Using age as the time variable, all-cause and cause-specific mortality were estimated between 2010 and 2017 with the Kaplan-Meier estimator and the cumulative incidence competing risk method, respectively. Sex-, education level-, health region- and age group-adjusted HRs for mortality were estimated using Cox regression models. RESULTS: We identified 36 095 RA, 18 700 PsA, and 16 524 axSpA patients (70%, 53%, and 45% women, respectively). RA and axSpA were associated with increased all-cause mortality (HR 1.45 [95% CI, 1.41-1.48] and HR 1.38 [95% CI, 1.28-1.38], respectively). Women but not men with PsA had a slightly increased mortality rate (HR 1.10 [95% CI, 1.00-1.21] among women and 1.02 [95% CI 0.93-1.11] among men). For all patient groups as well as for the general population, the three leading causes of death were cardiovascular diseases, neoplasms and respiratory diseases. RA patients had increased mortality from all of these causes, while axSpA patients had increased mortality from cardiovascular and respiratory diseases. CONCLUSION: Even in the era of modern treatments for IJDs, patients with RA and axSpA still have shortened life expectancy. Our findings warrant further attention to the prevention and management of comorbidities.
35052812 Postprandial Hyperlipidemia: Association with Inflammation and Subclinical Atherosclerosis 2022 Jan 8 OBJECTIVE: To describe postprandial lipidemia in patients with rheumatoid arthritis (RA) and to analyze its association with subclinical atherosclerosis and inflammatory activity. METHODS: Observational study of 80 cases of RA and 80 sex- and age-matched controls. We excluded individuals with dyslipidemia. Postprandial hyperlipidemia (PPHL) was defined as postprandial triglycerides >220 mg/dL and/or postprandial ApoB48 levels >75th percentile (>p75). Plasma lipids, cholesterol, triglycerides, ApoB48, and total ApoB were evaluated at baseline and after a meal. Other variables analyzed included subclinical atherosclerosis (defined as presence of carotid atheromatous plaque), inflammatory activity (disease activity score (DAS28-ESR)), cytokines, apolipoproteins, and physical activity. A multivariate analysis was performed to identify factors associated with PPHL in patients with RA. RESULTS: A total of 75 patients with RA and 67 healthy controls fulfilled the inclusion criteria. PPHL was more frequent in patients with RA than controls (No. (%), 29 (38.70) vs. 15 (22.40); p = 0.036), as was subclinical atherosclerosis (No. (%), 22 (30.10) vs. 10 (14.90); p = 0.032). PPHL in patients with RA was associated with subclinical atherosclerosis (OR (95% CI) 4.69 (1.09-12.11); p = 0.037), TNF-α (OR (95% CI) 2.00 (1.00-3.98); p = 0.048), high-sensitivity C-reactive protein (OR (95% CI) 1.10 (1.01-1.19); p = 0.027), and baseline triglycerides (OR (95% CI) 1.02 (1.00-1.04); p = 0.049). CONCLUSION: PPHL was more frequent in patients with RA than in controls. PPHL in patients with RA was associated with inflammation and subclinical atherosclerosis.
35289841 Associations of the MUC5B Promoter Variant with Timing of Interstitial Lung Disease and Rh 2022 Mar 15 OBJECTIVE: To investigate the associations of the common MUC5B promoter variant with timing of RA-associated interstitial lung disease (RA-ILD) and RA onset. METHODS: We identified patients with RA meeting 2010 ACR/EULAR criteria and available genotype information in the Mass General Brigham Biobank, a multi-hospital biospecimen and clinical data collection research study. We determined RA-ILD presence by reviewing all RA patients who had computed tomography (CT) imaging, lung biopsy, or autopsy results. We determined the dates of RA and RA-ILD diagnoses by manual record review. We examined the associations of the MUC5B promoter variant (G > T at rs35705950) with RA-ILD, RA-ILD occurring before or within 2 years of RA diagnosis, and RA diagnosis at age >55 years. We used multivariable logistic regression to estimate odds ratios (OR) for each outcome by MUC5B promoter variant status, adjusting for potential confounders including genetic ancestry and smoking. RESULTS: We identified 1,005 RA patients with available genotype data for rs35705950 (mean age 45 years; 79% women; 81% European ancestry). The MUC5B promoter variant was present in 155 (15.4%) and was associated with RA-ILD (multivariable OR 3.34 [95%CI 1.97-5.60]), RA-ILD before or within 2 years of RA diagnosis (OR 4.01 [95%1.78-8.80]), and RA onset after age 55 years (OR 1.52, [95%CI 1.08-2.12]). CONCLUSIONS: The common MUC5B promoter variant was associated with RA-ILD onset earlier in the RA disease course and older age of RA onset. These findings suggest that MUC5B may impact RA-ILD risk early in the RA disease course, particularly in patients with older-onset RA.
35196494 JAK1 signaling in dendritic cells promotes peripheral tolerance in autoimmunity through PD 2022 Feb 22 Dendritic cells (DCs) induce peripheral T cell tolerance, but cell-intrinsic signaling cascades governing their stable tolerogenesis remain poorly defined. Janus Kinase 1 (JAK1) transduces cytokine-receptor signaling, and JAK inhibitors (Jakinibs), including JAK1-specific filgotinib, break inflammatory cycles in autoimmunity. Here, we report in heterogeneous DC populations of multiple secondary lymphoid organs that JAK1 promotes peripheral T cell tolerance during experimental autoimmune encephalomyelitis (EAE). Mice harboring DC-specific JAK1 deletion exhibit elevated peripheral CD4(+) T cell expansion, less regulatory T cells (Tregs), and worse EAE outcomes, whereas adoptive DC transfer ameliorates EAE pathogenesis by inducing peripheral Tregs, programmed cell death ligand 1 (PD-L1) dependently. This tolerogenic program is substantially reduced upon the transfer of JAK1-deficient DCs. DC-intrinsic IFN-γ-JAK1-STAT1 signaling induces PD-L1, which is required for DCs to convert CD4(+) T cells into Tregs in vitro and attenuated upon JAK1 deficiency and filgotinib treatment. Thus, DC-intrinsic JAK1 promotes peripheral tolerance, suggesting potential unwarranted DC-mediated effects of Jakinibs in autoimmune diseases.
34376342 Crossed Screw Fixation Versus Dorsal Plating for First Metatarsophalangeal Joint Arthrodes 2022 Jan Multiple fixation techniques for first metatarsophalangeal joint arthrodesis have been described with an average fusion rate of 93.5%. This retrospective cohort study assesses the association between crossed screws (vs dorsal plating) and medical comorbidities and the outcome radiographic union. Bivariate tests of association and multivariable logistic regression were employed to assess differences across fixation type and outcomes. We identified 305 patients who underwent a first metatarsophalangeal joint arthrodesis during the study period. Crossed screw fixation was used in 158 (51.8%) patients while dorsal plating (tubular or anatomic locking plate) was used in 147 (48.2%) patients. Dorsal plating was utilized more often in patients with rheumatoid arthritis (p = .019) and history of smoking (p = .044). At 12 weeks post-operatively there were no significant differences in fusion rates between the two groups (crossed screw group = 95.3% vs dorsal plate group (referent) = 93.5%, Adjusted odds ratio (AOR) 1.39, 95% confidence interval [CI] 0.45-4.26). Not smoking was associated with a greater odds of fusion at 12 weeks (96.2% for nonsmokers vs 75.0% for smokers (referent), AOR 0.07, 95% CI 0.02-0.28). Lower body mass index was associated with a greater odds of fusion at 12 weeks (AOR 0.90, 95% CI 0.82-0.99). Surgeons allowed weightbearing earlier with dorsal plate fixation (2 weeks (interquartile range [IQR] 2.6) versus 5 weeks (IQR 2.6) for crossed screw fixation, p = .001). Patients with multiple medical comorbidities were more likely to require revision surgery than patients having 0-1 comorbidities (p < .05). Crossed screws can provide an inexpensive yet effective option for first metatarsophalangeal joint arthrodesis.
35232809 Impact of Tofacitinib on Components of the ACR Response Criteria: Post Hoc Analysis of Pha 2022 Jun OBJECTIVE: To evaluate the effect of tofacitinib (TOF) on American College of Rheumatology (ACR) response criteria components in patients with rheumatoid arthritis (RA). METHODS: This post hoc analysis pooled data from RA phase III randomized controlled trials (RCTs) assessing TOF 5 or 10 mg BID, adalimumab (ADA), or placebo, with conventional synthetic disease-modifying antirheumatic drugs, and a phase IIIb/IV RCT assessing TOF 5 mg BID monotherapy, TOF 5 mg BID with methotrexate (MTX), or ADA with MTX. Outcomes included proportions of patients achieving ACR20/50/70 responses and ≥ 20/50/70% improvement rates in ACR components at week 2 and months 1, 3, and 6; and mean percent improvement in ACR components and Clinical or Simplified Disease Activity Index (CDAI or SDAI) low disease activity or remission rates, at month 3, for ACR20/50/70 responders. RESULTS: Across treatment groups, ≥ 20/50/70% improvement rates were numerically higher for most physician- vs patient-reported measures. In phase III RCTs, at earlier timepoints, ≥ 50/70% improvements in patient global assessment of disease activity, pain, and physician global assessment were similar. Among ACR20 responders receiving TOF, mean percent improvements for tender and swollen joint counts were > 70% at month 3. CDAI/SDAI remission was achieved at month 3 by 27.8-45.0% of ACR70 responders receiving TOF. CONCLUSION: Among ACR20 responders treated with TOF, physician-reported components particularly exceeded 20% response improvement. At month 3, disease state generally did not corroborate ACR70 response criteria. Divergences between physician- and patient-reported measures highlight the importance of identifying appropriate patient-reported outcome targets to manage RA symptoms in clinical practice. (ClinicalTrials.gov: NCT00847613/NCT00856544/NCT00853385/NCT02187055).
35028144 Neutrophilic dermatoses in a seronegative rheumatoid arthritis patient: A case report. 2022 Jan Rheumatoid arthritis (RA) is a chronic inflammatory disease, characterized by symmetric and destructive polyarthritis with a broad-spectrum clinical manifestation of various organs. RND is an unusual distinctive manifestation of RA and typically develops in severe RA. This report aims to present an unusual and a rare neutrophilic skin condition, in a seronegative RA Sudanese patient. A 51-year-old woman was diagnosed with RA three years ago and a history of bilateral polyarthritis, presented with a skin rash involving her extremities and abdomen. Clinical examination of her skin revealed the presence of maculopapular lesions affecting the extensor surfaces of the lower extremities and the lower part of the abdomen with hyperpigmentation. Hand X-ray demonstrated periarticular osteopenia, and laboratory and immunological studies that include C-reactive protein, erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), anticitrullinated peptide antibodies (ACPAs), and antinuclear factor in addition to skin biopsy were all suggested a diagnosis of neutrophilic dermatosis. The patient received steroids for the skin lesion still no significant improvement was seen, and then, cyclosporin 100 mg was administrated twice/ day with close monitoring, and two weeks later marked improvement was shown.
35135554 Relationship of cytochrome P450 gene polymorphisms with blood concentrations of hydroxychl 2022 Feb 8 BACKGROUND: Hydroxychloroquine (HCQ) is a cornerstone therapy for systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). This study aimed to investigate the relationship of cytochrome P450 (CYP450) gene polymorphisms with blood concentrations of HCQ and its metabolites and adverse drug reactions (ADRs) in patients with SLE and RA. METHODS: A cohort of 146 patients with SLE and RA treated with HCQ was reviewed. The ADRs of the patients were recorded. The blood concentrations of HCQ and its metabolites were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Genotyping of single nucleotide polymorphisms (SNPs) in CYP450, a metabolic enzyme involved in the HCQ metabolic pathway, was performed using a MassARRAY system. The chi-square test, T-test, and one-way analysis of variance were used to analyse data. RESULTS: Among 29 candidate SNPs, we found that CYP3A4 (rs3735451) was significantly associated with blood levels of HCQ and its metabolites in both the unadjusted model and adjusted model (patients taking HCQ for > 10 years) (P < 0.05). For CYP3A5 (rs776746), a greater risk of skin and mucous membrane ADRs was associated with the TT genotype than with the CT + CC genotypes (P = 0.033). For CYP2C8 (rs1058932), the AG genotype carried a greater risk of abnormal renal function than the AA + GG genotype (P = 0.017); for rs10882526, the GG genotype carried a greater risk of ophthalmic ADRs than the AA + AG genotypes (P = 0.026). CONCLUSIONS: The CYP2C8 (rs1058932 and rs10882526) and CYP3A5 (rs776746) polymorphisms are likely involved in the ADRs of HCQ. Gene polymorphism analysis of CYP450 and therapeutic drug monitoring of HCQ and its metabolites might be useful to optimise HCQ administration and predict ADRs.
35148758 Methotrexate-loaded nanoparticles ameliorate experimental model of autoimmune arthritis by 2022 Feb 11 BACKGROUND: Rheumatoid arthritis (RA) is a progressive systemic autoimmune disease that is characterized by infiltration of inflammatory cells into the hyperplastic synovial tissue, resulting in subsequent destruction of adjacent articular cartilage and bone. Methotrexate (MTX), the first conventional disease-modifying antirheumatic drug (DMARD), could alleviate articular damage in RA and is implicated in humoral and cellular immune responses. However, MTX has several side effects, so efficient delivery of low-dose MTX is important. METHODS: To investigate the efficacy of MTX-loaded nanoparticles (MTX-NPs) against experimental model of RA, free MTX or MTX-NPs were administered as subcutaneous route to mice with collagen-induced arthritis (CIA) at 3 weeks after CII immunization. The levels of inflammatory factors in tissues were determined by immunohistochemistry, confocal microscopy, real-time PCR, and flow cytometry. RESULTS: MTX-NPs ameliorated arthritic severity and joint destruction in collagen-induced arthritis (CIA) mice compared to free MTX-treated CIA mice. The levels of inflammatory cytokines, including interleukin (IL)-1β, tumor necrosis factor-α, and vascular endothelial growth factor, were reduced in MTX-NPs-treated mice. Number of CD4 + IL-17 + cells decreased whereas the number of CD4 + CD25 + Foxp3 + cells increased in spleens from MTX- NPs-treated CIA mice compared to MTX-treated CIA mice. The frequency of CD19 + CD25 + Foxp3 + regulatory B cells increased in ex vivo splenocytes from MTX-loaded NPs-treated CIA mice compared to MTX-treated CIA mice. CONCLUSION: The results suggest that MTX-loaded NPs have therapeutic potential for RA.
35123251 The risk factors for self-reported fibromyalgia with and without multiple somatic symptoms 2022 Apr OBJECTIVE: The numerous risk factors for fibromyalgia reflect its heterogeneous nature. This study assessed whether the predictors of fibromyalgia onset vary according to number of prior somatic symptoms. METHODS: The prospective, population-based Lifelines cohort study included 138,617 adults without fibromyalgia or marked muscle pain. At baseline socio-demographic status, physical and psychiatric disorders, psycho-social and behavioural variables were assessed as potential predictors. At follow-up (mean 2.4 years later) new onsets of fibromyalgia were recorded by self-report. The predictors of new onsets of self-reported fibromyalgia were assessed using logistic regression with interaction terms between key variables and number of somatic symptoms. RESULTS: At follow-up 679 (0.5%) participants reported new onset fibromyalgia. The strongest predictors were: female sex, rheumatoid and osteo-arthritis, IBS, impaired sleep, migraine, few years of education and impairment by bodily pain. Interaction terms with somatic symptoms were significant for years of education, low income, rheumatoid arthritis and no. of analgesics; these were predictors only for fibromyalgia with few somatic symptoms. Participants with multiple somatic symptoms had a higher number of predictors than those with few somatic symptoms. CONCLUSION: This study suggests that people developing self-reported fibromyalgia with multiple pre-existing somatic symptoms have a high risk factor load reflecting risk factors for both fibromyalgia and multiple somatic symptoms. Self-reported fibromyalgia with few somatic symptoms has fewer predictors which may be specific to fibromyalgia. Future research could usefully study whether different pathophysiological mechanisms occur when fibromyalgia is preceded by high or low number of somatic symptoms.
34775770 Pharmacology and molecular docking study of cartilage protection of Chinese herbal medicin 2022 Feb BACKGROUND: This study aims to explore whether Fufang Shatai Heji (STHJ), as a mixture collected by a decoction of a variety of Chinese herbal medicines for immune system diseases, can improve the cartilage destruction of rheumatoid arthritis (RA). METHODS: The therapeutic effects of STHJ were studied using collagen induced arthritis (CIA) mice. The improvement effect of STHJ on synovitis and cartilage damage caused by arthritis was studied by joint pathological analysis. The inhibitory effect of STHJ on related degradation enzymes in cartilage was studied by immunohistochemistry and real-time polymerase chain reaction (PCR). The specific targets of STHJ were predicted by molecular docking. RESULTS: After successfully inducing CIA, the paws of the mice showed significant swelling, and athological analysis of the ankle and knee joints also showed significant cartilage destruction and synovial hyperplasia. However, synovial hyperplasia and cartilage destruction were markedly alleviated after administration of STHJ. And after STHJ treatment, the expression of ADAMTS-4, ADAMTS-5, MMP-9 and MMP-13, in the cartilage layer of CIA mice was significantly inhibited. Through molecular docking assays, we proved that acteoside in STHJ could directly bind to the Glu111, Phe110 residues in MMP-9 and glycyrrhizic acid in STHJ bind to the Glu382, Asn433 residues in MMP-13. CONCLUSIONS: Our results suggested that STHJ may alleviate synovial hyperplasia and cartilage destruction in CIA mice and protect cartilage by inhibiting the expression of MMP-9 and other enzymes.
35653890 Gender differences and pharmacological regulation of angiogenesis induced by synovial flui 2022 May 30 Several mediators including cytokines, growth factors and metalloproteinases (MMP) modulate pathological angiogenesis associated with inflammatory arthritis. The biological factors underlying sex disparities in the incidence and severity of rheumatic musculoskeletal diseases are only partially understood. We hypothesized that synovial fluids (SFs) from rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients would impact on endothelial biology in a sexually dimorphic fashion. Immune cell counts and levels of pro-angiogenic cytokines found in SFs from RA and PsA patients (n = 17) were higher than in osteoarthritis patients (n = 6). Synovial VEGF concentration was significantly higher in male than in female RA patients. Zymography revealed that SFs comprised solely MMP-9 and MMP-2, with significantly higher MMP-9 levels in male than female RA patients. Using in vitro approaches that mimic the major steps of the angiogenic process, SFs from RA and PsA patients induced endothelial migration and formation of capillary-like structures compared to control. Notably, endothelial cells from female donors displayed enhanced angiogenic response to SFs with respect to males. Treatment with the established anti-angiogenic agent digitoxin prevented activation of focal adhesion kinase and SF-induced in vitro angiogenesis. Thus, despite higher synovial VEGF and MMP-9 levels in male patients, the responsiveness of vascular endothelium to SF priming was higher in females, suggesting that gender differences in angiogenic responses were mainly related to the endothelial genotype. These findings may have implications for pathogenesis and targeted therapies of inflammatory arthritis.
35645418 Methods of assessment of joint involvement in various systemic connective tissue diseases. 2022 Joint involvement is one of the most common clinical manifestations of systemic connective tissue diseases (CTD). Joint symptoms can take various forms, ranging from joint pain to mono-arthritis or symmetrical poly-arthritis. In most cases, arthritis takes a non-destructive form, such as in the course of systemic lupus erythematosus or primary Sjögren's syndrome, to destructive arthritis in overlap syndromes of CTD with rheumatoid arthritis. In addition, apart from the wide variety of forms of joint involvement, it should be noted that joint symptoms may be one of the domains suggesting a severe course of the disease. The study attempts to present the methods of assessing the involvement of the locomotor system. The search for appropriate scales to determine the degree of joint involvement is important in assessing the severity of joint changes, has an impact on the overall degree of disease activity, and allows for timely implementation of appropriate treatment.
34787826 A case of smoldering antineutrophil cytoplasmic antibody-associated vasculitis development 2022 May Various forms of glomerular lesions have been described in primary Sjögren's syndrome (pSjS); however, myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is rarely reported, and the disease onset and clinical course of ANCA-associated vasculitis (AAV) complicated by pSjS are not well understood. A 51-year-old woman was referred to our hospital because of mild proteinuria and microscopic hematuria. She fulfilled the classification criteria for pSjS. We performed a kidney biopsy; however, it revealed no characteristic findings for pSjS, vasculitis, or other autoimmune diseases, including systemic lupus erythematosus. After 9 months, urinalysis abnormalities worsened and renal function was slowly declining, and ANCA was found to be positive. A second kidney biopsy was performed, revealing MPO-ANCA-associated pauci-immune segmental necrotizing glomerulonephritis with crescent formation. Even though immunofluorescence microscopy did not reveal any positive findings, additional electron microscopy demonstrated the presence of mesangial electron-dense deposits in both kidney biopsies. Based on kidney biopsy results and sequential serum ANCA measurements, we considered that smoldering ANCA-associated vasculitis had developed in this patient as this can develop during the clinical course of pSjS. She responded well to steroid therapy. Serum measurement, especially perinuclear, ANCA levels can be useful in patients with pSjS to detect the onset of ANCA-associated vasculitis, even in the absence of acute renal deterioration or severe urinary abnormalities.
35597820 Bone marrow-derived macrophages from a murine model of Sjögren's syndrome demonstrate an 2022 May 21 Sjögren's syndrome (SjS) is a female-dominated autoimmune disease involving lymphocytic infiltration of the exocrine glands. We have previously demonstrated cleavage of the TAM (Tyro3, Axl, Mer) receptor Mer is enhanced in SjS, leading to defective efferocytosis. Mer also plays a role in modulating phagocyte inflammatory response to apoptotic cells. Here we investigated the SjS macrophage response to apoptotic cells (AC). Bone marrow-derived macrophages (BMDMs) from SjS-susceptible (SjS(s)) C57BL/6.NOD-Aec1Aec2 mice and C57BL/6 (B6) controls were treated with either AC or CpG-oligodeoxynucleotides. RNA was collected from macrophages and bulk sequencing was performed to analyze transcripts. Cytokine expression was confirmed by Bio-plex. RT-qPCR was used to determine toll-like receptor (TLR) 7 and 9 involvement in BMDM inflammatory response to apoptotic cells. SjS(S) BMDMs exhibited a distinct transcriptional profile involving upregulation of a broad array of inflammatory genes that were not elevated in B6 BMDMs by AC. Inhibition of TLR 7 and 9 was found to limit the inflammatory response of SjS(S) BMDMs to ACs. ACs elicit an inflammatory reaction in SjS(S) BMDMs distinct from that observed in B6 BMDMs. This discovery of aberrant macrophage behavior in SjS in conjunction with previously described efferocytosis defects suggests an expanded role for macrophages in SjS, where uncleared dead cells stimulate an inflammatory response through macrophage TLRs recruiting lymphocytes, participating in co-stimulation and establishing an environment conducive to autoimmunity.
35219608 Drug allergy and autoimmune diseases. 2022 Apr Systemic autoimmune diseases are reportedly associated with a high frequency of drug allergies. In particular, systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), and adult-onset Still's disease (AOSD) have recently drawn attention. Based on previous reports, drug allergies have been reported in 17.1-63%, 7-40.1%, and 17.6-54% of patients with SS, SLE, and AOSD patients, respectively. Antimicrobial agents, including sulfa drugs and nonsteroidal anti-inflammatory drugs, are the most common causative agents of drug allergies. However, few studies have examined in detail the relationship between drug eruptions, a major symptom of drug allergy, and systemic autoimmune diseases, and their actual status remains unclear. These autoimmune diseases commonly exhibit a diverse range of skin manifestations in the course of these diseases, rendering it may be difficult to determine whether it is a true drug eruption. Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), a fatal, severe drug eruption, has also been associated with autoimmune diseases. The development of SS-like symptoms after SJS/TEN onset and high prevalence of anti-SS-A antibodies in SJS/TEN are intriguing observations. Although the presence of SLE is known to be a risk factor for SJS/TEN, common pathological conditions, such as excessive immune status, abnormal function of regulatory T cells, and neutrophil extracellular traps in autoimmune diseases such as SS and SLE, are potentially involved in the development of drug eruptions.
35489168 Psychological stress in rheumatoid arthritis: a systematic scoping review. 2022 Apr 21 BACKGROUND: Rheumatoid arthritis (RA) considerably impacts patients' mental health. However, it is largely unclear how people suffering from RA experience psychological stress beyond depression or anxiety, and what drives stress in these patients. OBJECTIVE: To examine the impact of RA on psychological stress, as follows: 1) How is stress defined and described in studies on RA? 2) Do patients with RA experience more stress than the general population or people suffering from other chronic conditions? 3) What are risk factors for developing stress in this context? METHODS: We systematically searched EMBASE, PubMed, Web of Science Core Collection and Cochrane Library for English language peer-reviewed reports published up to 19 April 2020. Eligible studies included any measure or definition of psychological stress as an outcome in patients with RA. Data were extracted on patient and study characteristics, instruments used to measure stress and predictors of stress, and were summarized descriptively. Study quality was assessed with the MINORS or AXIS-tool for longitudinal and cross-sectional studies, respectively. RESULTS: Among 11.115 potentially relevant studies, 16 studies were included. Remarkably, 13 different instruments to measure stress were reported in these studies. Different types of stress experienced by patients with RA included role stress, social stress, and work stress. Work stress and social stress, particularly resulting from interpersonal stressors, were reported as more prevalent in patients with RA compared to healthy controls. Stress at disease onset appeared more pronounced in patients with RA compared to people suffering from osteoarthritis, while psychological stress was reported as higher in patients with chronic pain syndromes compared to patients with RA. More disability, more pain, less social support, lower income, younger age and personality traits like excessive worrying, pessimism, and sensitivity to anxiety, seemed to increase the risk for higher stress levels. CONCLUSIONS: This scoping review is, to our knowledge, the first to address the important heterogeneity of the measurement tools and definitions of psychological stress in RA research. This review could provide a basis to standardize the concept of stress in people suffering from RA, with a view to proposing tailored stress-reducing interventions.
35059877 Diminished natural killer T-like cells correlates with aggravated primary Sjögren's syndr 2022 Apr OBJECTIVE: To reveal the characteristics and potential role of natural killer T-like cells (NKT-like cells) in the pathogenesis of primary Sjögren's syndrome (pSS). METHODS: Forty-six patients with pSS and 30 healthy subjects were enrolled in the study. The frequencies and cell count of NKT-like cells as well as other lymphocyte subsets were analyzed by flow cytometry. The clinical and laboratory indicators of pSS patients were also collected. Then, the correlation between NKT-like cells and pSS patient manifestations was analyzed by Spearman's rank test. In addition, NKT-like cells before and after therapy were also compared. RESULTS: Both the number and the frequencies of NKT-like cells were significantly decreased in pSS patients. The counts of NKT-like cells were positively correlated with CD4(+) T cells (r = 0.464, P = 0.001), CD8(+) T cells (r = 0.363, P = 0.013), NK cells (r = 0.488, P = 0.001), and IgM levels (r = 0.443, P = 0.002), while negatively correlated with the disease duration (r =  - 0.33, P = 0.027). Moreover, after effective therapy, NKT-like cells were recovered both in the cell counts and frequencies. CONCLUSION: In pSS, NKT-like cells were fundamentally decreased, potentially contributing to the disease pathogenesis. Modulating the status of NKT-like cells might provide a novel strategy for treating the disease. KEY POINTS: • NKT-like cells were significantly decreased in pSS patients. • NKT-like cells were correlated with pSS patient manifestations. • NKT-like cells might be serverd as a new marker for assessing the status of pSS.
34996068 Longitudinal Tracking of Extractable Nuclear Antigen (ENA) Antibodies in a Quaternary Hosp 2022 Jan 5 BACKGROUND: Antiextractable nuclear antigens (anti-ENAs) are regarded as diagnostic tests with no established value for serial monitoring. We therefore sought to establish the stability over time of anti-ENAs in a large diagnostic immunopathology laboratory. METHODS: A retrospective review of all patients who had a serial anti-ENA ordered at the Westmead Hospital (Sydney, Australia) was performed over 24 months. Anti-ENA characterization was performed using line immunoassay, and historical data were available from 2013 onward. The earliest available densitometry readings were compared with the latest available to examine for a change in quantitation or qualitative (serostatus) result (from negative to positive, and vice versa). Medical records were examined for clinical correlations. RESULTS: A total of 283 patients (24.1%) had serial testing of anti-ENA in the audit period, with each patient having an average of 3.9 ± 2.9 tests each. Most patients were diagnosed with systemic lupus erythematosus or primary Sjögren's syndrome. About 25% and 58% of patients had a qualitative and quantitative change, respectively, in at least 1 anti-ENA in the study period. Changes in anti-ENA levels correlated with erythrocyte sedimentation rate and disease activity. Increasing duration between serial tests increased the probability of observing a change in anti-ENA levels. CONCLUSION: Certain anti-ENAs are dynamic autoantibodies that may have significance for monitoring disease activity. Laboratories may consider reporting quantitative results. Further disease- and autoantibody-specific studies are required to determine the clinical significance of changes in anti-ENAs.
34782448 Sex-related Differences in Systemic Sclerosis: A Multicenter Cross-sectional Study From th 2022 Feb OBJECTIVE: There is still a great deal to learn about the influence of sex in systemic sclerosis (SSc). In this respect, national registries provide large and homogeneous patient cohorts for analytical studies. We therefore investigated a wide-ranging and well-characterized SSc series with the aim of identifying sex differences in disease expression, with a special focus on demographic, clinical, and serological characteristics. METHODS: A multicenter SSc cohort of 2281 patients, including 247 men, was recruited in the Italian Systemic sclerosis PRogression INvestiGation (SPRING) registry. Demographic data, disease manifestations, serological profile, and internal organ involvement were compared. RESULTS: The overall female/male ratio was 8.2:1. Female/male ratios for limited cutaneous SSc, diffuse cutaneous SSc, and SSc sine scleroderma subsets were 8.7:1, 4.9:1, and 10.7:1, respectively. A shorter time from onset of Raynaud phenomenon to SSc diagnosis, an increased prevalence of the diffuse cutaneous subset, renal crisis, and digital ulcers were found in males, whereas a significantly higher percentage of sicca syndrome, serum antinuclear antibodies, antiextractable nuclear antigens, anti-La/SSB, and anticentromere protein B was detected in the female group. Males exhibited lower left ventricular ejection fraction, as well as higher prevalence of conduction blocks, arrhythmias, ground glass, and honeycombing. Moreover, forced vital capacity and total lung capacity were medially lower in men than in women. Finally, males were more frequently treated with immunosuppressive drugs. CONCLUSION: Our study further supports the presence of several sex-related differences in patients with SSc. These differences were pronounced in the severity of cutaneous, peripheral vascular, and cardiopulmonary involvement for male patients, whereas an increased prevalence of sicca syndrome and a specific autoantibody profile characterized the female sex.