Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
---|---|---|---|---|
31068953 | Cytomegalovirus Infection May Trigger Adult-Onset Still's Disease Onset or Relapses. | 2019 | Previous studies have revealed that several micro-organisms, especially DNA viruses, have been associated with adult-onset Still's disease (AOSD). However, there are no studies on the relationship between the presence of viral infections in AOSD patients with disease occurrence and reactivation. In the present study, we aimed to investigate the presence of antibodies against virus, virus DNA load and nucleic acid sensors in AOSD patients. Anti-viral antibodies were measured by enzyme-linked immunosorbent assay (ELISA) in plasma samples from 100 AOSD patients and 70 healthy controls (HCs). The copy number of cytomegalovirus (CMV) DNA in 100 AOSD patients was detected by PCR. The expression levels of nucleic acid sensors interferon gamma-inducible protein 16 (IFI16) and absent in melanoma 2 (AIM2) in peripheral blood mononuclear cell (PBMC) and skin from AOSD patients and HCs were analyzed by PCR and immunohistochemistry. The levels of antibodies against CMV were significantly higher in AOSD patients compared to HCs. Moreover, the level of anti-CMV IgM antibody was significantly increased in patients with fever, sore throat, arthralgia and rash. CMV DNA was found in plasma of AOSD patients with disease new-onset and relapse. Furthermore, the copy number of CMV DNA significantly increased in patients with fever, sore throat, arthralgia and rash. And the significant associations of the CMV DNA level with the levels of leukocytes, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) were observed. Moreover, we found an upregulation of cytoplasmic DNA-sensing receptor IFI16 and AIM2 in PBMC and skin from AOSD patients. In conclusion, our results showed that CMV infection may play a role in the initiation or amplification of inflammatory responses in AOSD. | |
30877775 | Aspirin Triggered Resolvin D1 reduces inflammation and restores saliva secretion in a Sjö | 2019 Jul 1 | OBJECTIVES: SS is characterized by chronic inflammation of the salivary glands leading to loss of secretory function, thereby suggesting specialized pro-resolving mediators targeting inflammation to be a viable option for treating SS. Previous studies demonstrated that aspirin-triggered resolvin D1 (AT-RvD1) prevents chronic inflammation and enhances saliva secretion in a SS-like mouse model when applied before disease onset. However, this therapy cannot be used in SS patients given that diagnosis occurs post-disease onset and no reliable screening methods exist. Therefore, we examined whether treatment with AT-RvD1 reduces SS-like features in a mouse model post-disease onset. METHODS: Tail vein injections were performed in a SS-like mouse model both with and without AT-RvD1 post-disease onset for 8 weeks, with salivary gland function and inflammatory status subsequently determined. RESULTS: Treatment of a SS-like mouse model with AT-RvD1 post-disease onset restores saliva secretion in both females and males. Moreover, although AT-RvD1 treatment does not reduce the overall submandibular gland lymphocytic infiltration, it does reduce the number of T helper 17 cells within the infiltrates in both sexes. Finally, AT-RvD1 reduces SS-associated pro-inflammatory cytokine gene and protein expression levels in submandibular glands from female but not male mice. CONCLUSION: AT-RvD1 treatment administered post-disease onset reduces T helper 17 cells and successfully restores salivary gland function in a SS mouse model with variable effects noted by sex, thus warranting further examination of both the causes for the sex differences and the mechanisms responsible for the observed treatment effect. | |
31424086 | Cytometry by time of flight identifies distinct signatures in patients with systemic scler | 2020 Jan | Systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and primary Sjögrens syndrome (pSS) are clinically distinct systemic autoimmune diseases (SADs) that share molecular pathways. We quantified the frequency of circulating immune-cells in 169 patients with these SADs and 44 healty controls (HC) using mass-cytometry and assessed the diagnostic value of these results. Alterations in the frequency of immune-cell subsets were present in all SADs compared to HC. Most alterations, including a decrease of CD56(hi) NK-cells in SSc and IgM(+) Bcells in pSS, were disease specific; only a reduced frequency of plasmacytoid dendritic cells was common between all SADs Strikingly, hierarchical clustering of SSc patients identified 4 clusters associated with different clinical phenotypes, and 9 of the 12 cell subset-alterations in SSc were also present during the preclinical-phase of the disease. Additionally, we found a strong association between the use of prednisone and alterations in B-cell subsets. Although differences in immune-cell frequencies between these SADs are apparent, the discriminative value thereof is too low for diagnostic purposes. Within each disease, mass cytometry analyses revealed distinct patterns between endophenotypes. Given the lack of tools enabling early diagnosis of SSc, our results justify further research into the value of cellular phenotyping as a diagnostic aid. | |
30794472 | Comparison of Meibomian Gland Imaging Findings and Lipid Layer Thickness between Primary S | 2020 | Purpose: To compare meibomian gland (MG) imaging findings and lipid layer thickness (LLT) between patients with primary Sjögren syndrome (SS) dry eyes (DE) and non-SS DE.Methods: A total of 60 patients-30 with SS DE and 30 with non-SS DE were evaluated. Infrared image findings of MGs and LLT were assessed using the LipiView II interferometer.Results: The maximum LLT was significantly lower in the SS DE group. SS DE exhibited significantly higher MG dropout compared to the non-SS DE. Average and maximal LLT showed significant negative correlations with MG dropout in both groups (p<0.05). Conjunctival staining scores showed significant correlations with average and maximum LLT and MG dropout values in the SS DE group (p<0.05).Conclusion: These findings suggest that the new interferometer will be useful in understanding the pathophysiology of SS DE. | |
28532741 | Coexistence of sarcoidosis and adult onset Still disease. | 2019 Sep | Sarcoidosis is a chronic, inflammatory disease with unknown cause characterized by non-caseating granuloma formations. It can be presented with bilateral hilar lymphadenopathy, skin lesions, eye involvement and locomotor system findings. Adult onset Still disease (AOSD) is a chronic inflammatory disease which presents with fever, arthritis and typical skin rashes. The disease is rare and can be misdiagnosed due to the absence of typical clinical and laboratory findings. The association of sarcoidosis and AOSD has not been previously reported in the literature. Herein we reported the development of AOSD in a patient followed by the diagnosis of sarcoidosis. The patient did not respond to high-dose corticosteroids and methotrexate therapy, and the disease was under control with anti-IL-6 (Tocilizumab) drug. | |
31354737 | Neuro-Sjögren: Peripheral Neuropathy With Limb Weakness in Sjögren's Syndrome. | 2019 | Objective: Sjögren's syndrome is a heterogeneous inflammatory disorder frequently involving peripheral nerves with a wide spectrum of sensory modalities and distribution patterns. The objective of this cross-sectional study was to determine characteristics of Sjögren's syndrome as a cause for severe neuropathy with limb weakness. Methods: One hundred and eighty four patients with polyneuropathy associated with limb weakness underwent routine diagnostics including investigations for Sjögren's syndrome. Forty-four patients with Sjögren's syndrome (ACR-EULAR classification criteria) and severe neuropathy were identified. Results: Sjögren's syndrome was found at a median age of 63 years and the gender distribution showed a balanced female-male ratio of 1:1. Anti-SSA(Ro) antibodies were detected in 48% while seronegative patients were diagnosed with Sjögren's syndrome based on sialadenitis on minor salivary gland biopsy with a focus score ≥1. The majority of patients (93%) were diagnosed with Sjögren's syndrome after neurological symptoms appeared. Limbs were symmetrically involved in 84% of patients (57% tetraparesis, 27% paraparesis). Sensory function was not affected in 11% of patients indicating that Sjögren's syndrome associated neuropathy can present as a pure motor syndrome. Electrophysiological measurements did not reveal pathognomonic findings (23% demyelinating pattern, 36% axonal pattern, 41% both demyelinating and axonal damage signs). More than half of our patients fulfilled the European Federation of Neurological Societies (EFNS) diagnostic criteria for CIDP indicating that distinction between Neuro-Sjögren and other causes of neuropathy such as CIDP is challenging. Interpretation: Our findings show that severe neuropathy with limb weakness is often associated with Sjögren's syndrome. This is of great importance in identifying and understanding the causes of immune mediated polyneuropathy. | |
30967862 | Ablation of the Chaperone Protein ERdj5 Results in a Sjögren's Syndrome-Like Phenotype in | 2019 | Objective: Sjögren's syndrome (SS) is a chronic autoimmune disorder that affects mainly the exocrine glands. Endoplasmic reticulum (ER) stress proteins have been suggested to participate in autoimmune and inflammatory responses, either acting as autoantigens, or by modulating factors of inflammation. The chaperone protein ERdj5 is an ER-resident disulfide reductase, required for the translocation of misfolded proteins during ER-associated protein degradation. In this study we investigated the role of ERdj5 in the salivary glands (SGs), in association with inflammation and autoimmunity. Methods: In situ expression of ERdj5 and XBP1 activation were studied immunohistochemically in minor SG tissues from primary SS patients and non-SS sicca-complaining controls. We used the mouse model of ERdj5 ablation and characterized its features: Histopathological, serological (antinuclear antibodies and cytokine levels), and functional (saliva flow rate). Results: ERdj5 was highly expressed in the minor SGs of SS patients, with stain intensity correlated to inflammatory lesion severity and anti-SSA/Ro positivity. Moreover, SS patients demonstrated higher XBP1 activation within the SGs. Remarkably, ablation of ERdj5 in mice conveyed many of the cardinal features of SS, like spontaneous inflammation in SGs with infiltrating T and B lymphocytes, distinct cytokine signature, excessive cell death, reduced saliva flow, and production of anti-SSA/Ro and anti-SSB/La autoantibodies. Notably, these features were more pronounced in female mice. Conclusions: Our findings suggest a critical connection between the function of the ER chaperone protein ERdj5 and autoimmune inflammatory responses in the SGs and provide evidence for a new, potent animal model of SS. | |
30927277 | Refractory macrophage activation syndrome in the setting of adult-onset Still disease with | 2019 Jul | A 19-year-old Caucasian female with adult-onset Still disease (AOSD) presented for evaluation of an acute clinical decompensation and atypical annular papules and plaques with purpura on the lower extremities. A punch biopsy demonstrated histiocytes with engulfed degenerated erythrocytes and lymphocytes, consistent with hemophagocytic lymphohistiocytosis (HLH). HLH, clinically referred to as macrophage activation syndrome, is a rare complication of AOSD and is life-threatening. Relevant clinical, laboratory, and histologic features of this diagnosis are reviewed. | |
30738190 | The risk of Sjogren's syndrome in the older adults with gout: A medicare claims study. | 2019 Oct | OBJECTIVES: In the absence of previous studies, our objective was to assess whether gout was associated with an increase or decrease in the risk of Sjogren's Syndrome (SS) in older adults, 65 years or older. METHODS: We used the 5% Medicare claims from 2006-2012. A multivariable Cox regression model assessed the association of gout with incident SS adjusting for age, sex, race, Charlson-Romano comorbidity index, and the use of medications for cardiovascular diseases (statins, beta-blockers, diuretics, ACE-inhibitors) and gout (allopurinol, febuxostat). Hazard ratios (HR) and 95% confidence intervals (CI) were calculated. RESULTS: There were 3,186 new cases of SS in the study cohort with crude incidence rates of SS of 30/100,000 person-years in patients without gout and 49/100,000 person-years in patients with gout. Multivariable-adjusted analyses showed that gout was independently associated with a higher hazard ratio of SS of 1.73 (95% CI, 1.45, 2.06). Sensitivity analyses that substituted continuous Charlson-Romano comorbidity index score with categorized score (model 2) or individual comorbidities plus three common cardiovascular diseases (hypertension, hyperlipidemia, and coronary artery disease; model 3), confirmed the main study findings with minimal attenuation of hazard ratio, 1.70 (95% CI, 1.43, 2.02) and 1.48 (95% CI, 1.25, 1.77), respectively. Younger age, female sex, White race and higher comorbidity score were associated with a higher hazard of SS. CONCLUSIONS: Gout was associated with more than 1.7-fold higher risk of incident SS in adults 65 years or older. This finding needs to be reproduced and the underlying mechanisms for this association need further study. | |
30799581 | Quantitative Analysis of Parotid Gland Secretion Function in Sjögren's Syndrome Patients | 2019 Mar | OBJECTIVE: To evaluate the secretory function of parotid glands by dynamic magnetic resonance (MR) sialography and determine the clinical performance of this technique in diagnosing and evaluating Sjögren's syndrome (SS) patients. MATERIALS AND METHODS: This study enrolled 29 healthy volunteers (25 women and 4 men; mean age, 34.8 ± 6.3 years; age range, 26-47 years) and 25 primary SS (pSS) patients (23 women and 2 men; mean age, 37.7 ± 7.9 years; age range, 25-50 years) with decreased secretory function. The volume of the parotid gland ducts was precisely measured for both groups at single pre- and 6 post-gustatory-stimulated phases. Time-dependent volume change ratio curves were generated, four parameters were derived from the curves: the slope of the increase in the first post-stimulation phase (slope(1st)), the peak value, the time-to-peak, the total saliva secretion post-stimulation. All values were used to quantitatively evaluate the secretory function of the parotid gland. The repeated measurement analysis, Mann-Whitney U test and receiver operating characteristic curve were applied. RESULTS: Time-dependent volume change ratio curves demonstrated that there is a statistically significant difference between the two groups (F = 8.750; p = 0.005). A quickly increasing curve was shown in the volunteer group, whereas a slowly increasing curve was shown in the pSS patient group. The slope1st, peak value and total saliva secretion post-stimulation of the patient group were significantly lower than those of the volunteer group (p = 0.005, p = 0.003, and p = 0.002, respectively). The time-to-peak between the two groups was not significantly different (p = 0.383). The slope1st can be used as a discriminator to diagnose SS patients (p = 0.015; odds ratio = 4.234; area under the curve = 0.726). CONCLUSION: Dynamic MR sialography is proven to be an effective method in evaluating salivary gland function and has a great potential in diagnosing and evaluating pSS patients. | |
30776147 | Danger signals in oral cavity-related diseases. | 2019 Jul | The oral cavity is a unique environment containing teeth juxtaposed with soft tissues, all of which are constantly bathed in microbial products and host-derived factors. While microbial dysbiosis in the oral cavity clearly leads to oral inflammatory disease, recent advances find that endogenous danger-associated molecular patterns (DAMPs) released from oral and salivary tissue also contribute to the progression of inflammatory and autoimmune disease, respectively. In contrast, DAMPs produced during oral fungal infection actually promote the resolution of infection. Here, we present a review of the literature suggesting a role for signaling by DAMPs, which may intersect with pathogen-associated molecular pattern (PAMP) signaling, in diseases that manifest in the oral cavity, specifically periodontal disease, oropharyngeal candidiasis, and Sjögren's syndrome. | |
31661988 | Juxtaposition of IL-1β and IFN-γ expression and apoptosis of keratinocytes in adult-onse | 2019 Dec | Backgroud: Recently, atypical persistent skin eruptions (APSEs) have been documented as a new manifestation of adult-onset Still's disease (AOSD), with a unique pathological feature of necrotic keratinocytes in the upper third of the epidermis, but the mechanism has not been elucidated. The aim of this study was to explore the potential mechanism of the unique pathological phenomenon of APSEs.Methods: Clinical and pathological data from 26 AOSD patients with APSEs and 6 with evanescent skin eruptions (ESEs) were reviewed. Fourteen APSE biopsies and 6 ESE biopsies were selected for multi-spectrum immunohistochemistry with 5 disease controls and 5 healthy controls.Results: The unique pathological manifestation was present in all APSE patients but was hardly found in ESE patients. There were more CD4 + T-cells infiltrated in the dermis of APSEs than in the dermis of ESEs. IL-1β and IFN-γ were specifically expressed in the upper third of the epidermis and were juxtaposed to the loci of the necrotic keratinocytes.Conclusion: Our findings showed important cellular and molecular derangements related to the APSE-specific pathological phenomena and helped to understand the pathogenesis of dyskeratosis in the epidermis. The findings could also pave a way to explore an effective intervention to this potentially life-threatening disorder. | |
31173212 | Interleukin‑12 exacerbates Sjögren's syndrome through induction of myeloid‑derived su | 2019 Aug | Interleukin (IL)‑12 modulates the generation and function of various immune cells and plays a vital role in the pathogenesis of Sjögren's syndrome (SS). Myeloid‑derived suppressor cells (MDSCs) are involved in autoimmune diseases by regulating various immune responses. However, it has not been confirmed whether inflammatory IL‑12 participates in the progression of SS via regulating MSDCs. In the present study, the plasma levels of IL‑12 were detected by ELISA in SS‑like non‑obese diabetic (NOD) mice. The mice were treated by intraperitoneal injection of IL‑12 and anti‑IL‑12 antibody, respectively, and then the salivary flow rate was detected. The pathology of submandibular glands was evaluated in tissue sections stained with hematoxylin and eosin. The proportion of MDSCs was assessed by flow cytometry. The results showed that plasma IL‑12 was significantly increased in the SS‑like NOD mice comparing with that noted in the control mice. The exogenous IL‑12 exacerbated SS‑like symptoms of NOD mice and promoted the generation of both bone marrow (BM) and splenic MDSCs in the SS‑like NOD mice. Of note, anti‑IL‑12 alleviated SS‑like symptoms of NOD mice and inhibited the generation of BM and splenic MDSCs. Moreover, the generation of MDSCs was crippled in the IL‑12‑deficient C57BL/6 (Il‑12‑/‑ B6) mice. Our findings suggest that aggravation of SS‑like symptoms by IL‑12 in NOD mice may be attributed to its promotion of MDSC development. | |
31131409 | Dysregulated miRNome of plasmacytoid dendritic cells from patients with Sjögren's syndrom | 2019 Dec 1 | OBJECTIVE: A considerable body of evidence supports a role for type-I IFN in the pathogenesis of primary SS (pSS). As plasmacytoid dendritic cells (pDCs) are a major source of type-I IFN, we investigated their molecular regulation by measuring expression of a large set of miRNAs. METHODS: pDCs were isolated from peripheral blood of pSS patients (n = 30) and healthy controls (n = 16) divided into two independent cohorts (discovery and replication). Screening of 758 miRNAs was assessed by an OpenArray quantitative PCR-based technique; replication of a set of identified miRNAs was performed by custom array. Functional annotation of miRNA targets was performed using pathway enrichment. Novel targets of miR-29a and miR-29c were identified using a proteomic approach (stable isotope labelling with amino acids in cell culture). RESULTS: In the discovery cohort, 20 miRNAs were differentially expressed in pSS pDCs compared with healthy control pDCs. Of these, differential expression of 10 miRNAs was confirmed in the replication cohort. The dysregulated miRNAs were involved in phosphoinositide 3-kinase-Ak strain transforming and mammalian target of rapamycin signalling, as well as regulation of cell death. In addition, a set of novel protein targets of miR-29a and miR-29c were identified, including five targets that were regulated by both miRs. CONCLUSION: The dysregulated miRNome in pDCs of patients with pSS is associated with aberrant regulation of processes at the centre of pDC function, including type-I IFN production and cell death. As miR-29a and miR-29c are pro-apoptotic factors and several of the novel targets identified here are regulators of apoptosis, their downregulation in patients with pSS is associated with enhanced pDC survival. | |
32232095 | Investigational treatment of rheumatoid arthritis with a vibrotactile device applied to th | 2019 | BACKGROUND: Rheumatoid arthritis (RA) is a chronic and debilitating inflammatory disease characterized by extensive joint tissue inflammation. Implantable bioelectronic devices targeting the inflammatory reflex reduce TNF production and inflammation in preclinical models of inflammatory disease, and in patients with RA and Crohn's disease. Here, we assessed the effect of applying a vibrotactile device to the cymba concha of the external ear on inflammatory responses in healthy subjects, as well as its effect on disease activity in RA patients. METHODS: Six healthy subjects received vibrotactile treatment at the cymba concha, and TNF production was analyzed at different time points post-stimulation. In a separate study, nineteen healthy subjects were enrolled in a randomized cross-over study, and effects of vibrotactile treatment at either the cymba concha or gastrocnemius on cytokine levels were assessed. In addition, the clinical efficacy of vibrotactile treatment on disease activity in RA was assessed in nine patients with RA in a prospective interventional study. RESULTS: Vibrotactile treatment at the cymba concha reduced TNF levels, and the suppressive effect persisted up to 24 h. In the cross-over study with 19 healthy subjects, vibrotactile treatment at the cymba concha but not at the gastrocnemius significantly reduced TNF, IL-1β, and IL-6 levels compared to pre-treatment baseline (TNF p < 0.05, IL-6 p < 0.01, IL-1β p < 0.001). In healthy subjects, vibrotactile treatment at the cymba concha inhibited TNF by 80%, IL-6 by 73%, and IL-1β by 50% as compared to pre-treatment baseline levels. In RA patients, a significant decrease in DAS28-CRP scores was observed two days post-vibrotactile stimulation at the cymba concha (DAS28-CRP score pre-treatment = 4.19 ± 0.33 vs post-treatment = 3.12 ± 0.25, p < 0.05). Disease activity remained significantly reduced 7 days following vibrotactile treatment (DAS28-CRP score 7 days post-treatment = 2.79 ± 0.21, p < 0.01). In addition, a persistent improvement in visual analogue scale scores, a patient derived measure of global health assessment, was observed in RA patients following vibrotactile treatment. CONCLUSION: Application of a vibrotactile device to the cymba concha inhibits peripheral blood production of TNF, IL-1β, and IL-6 in healthy subjects, and attenuates systemic inflammatory responses in RA patients. TRIAL REGISTRATIONS: ClinicalTrials.gov Identifier: NCT01569789 and NCT00859859. The AMC trial conducted in The Netherlands does not have a ClinicalTrials.gov Identifier. | |
30886991 | Tissue metabolite of type I collagen, C1M, and CRP predicts structural progression of rheu | 2019 | BACKGROUND: Biomarkers of rheumatoid arthritis (RA) disease activity typically measure inflammation or autoimmunity (e.g. CRP, RF). C1M and C3M, metabolites of type I and III collagen, are markers reflecting tissue metabolism. These markers have been documented to provide additional prognostic and predictive value compared to commonly used biomarkers. We investigated the relationship of high serum levels of C1M or C3M to radiographic progression, and benchmarked them to CRP and RF. METHODS: Placebo treated patients of the OSK1, 2 and 3 studies (Phase III clinical trials testing efficacy of fostamatinib) with baseline serum biomarkers C1M, C3M, CRP and RF were included (n(BL) = 474). Van der Heijde mTSS was calculated at baseline and 24-week (n(24) = 261). Progression was defined as moderate or rapid by ΔmTSS ≥0.5 or ≥ 5 units/year. Patients were divided into subgroups; low (L), high (H) or very high (V) C1M, C3M and CRP, or RF negative, positive and high positive. Difference in clinical parameters were analyzed by Mann-Whitney or χ(2)tests, and modelling for prediction of progression by logistic regression including covariates (age, gender, BMI, and clinical assessment scores). RESULTS: Levels of C1M, C3M, CRP and RF were significantly (p < 0.05) associated with measures of disease activity and mTSS at baseline. For prognostic measures, there were 2.5 and 4-fold as many rapid progressors in the C1M(H) and CRP(H) (p < 0.05), and in the C1M(V) and CRP(V) groups (p < 0.001) compared C1M(L) and CRP(L), respectively. C1M and CRP performed similarly in the predictive analysis, where high levels predicted moderate and rapid progression with odds ratio of 2.1 to 3.8 and 3.7 to 13.1 after adjustment for covariates. C3M and RF did not provide prognostic value alone. DISCUSSION: Serum C1M and CRP showed prognostic value and may be tools for enrichment of clinical trials with structural progressor. The two markers reflect two different aspect of disease pathogenesis (tissue turnover vs. inflammation), thus may provide individual and supplementary information. | |
32118001 | Enalapril Influence on Arterial Stiffness in Rheumatoid Arthritis Women: A Randomized Clin | 2019 | Introduction: Cardiovascular parameters disruption can be found in patients at early stages of rheumatoid arthritis (RA). The primary endpoint of this study was the reduction of arterial stiffness in RA patients without traditional cardiovascular risk factors or previous comorbidities, measured by cardio-ankle vascular index (CAVI) through the enalapril intervention. The secondary endpoints were the enalapril influence on carotid femoral pulse wave velocity (cfPWV), carotid intima media thickness (cIMT), carotid artery distensibility (cDistensibility), Young's incremental elastic modulus (Einc)]. Materials and Methods: Fifty-three patients were enrolled in a clinical, randomized, closed-label trial. The subjects were randomly assigned into two groups: One receiving 5 mg of enalapril (27) or placebo (26), both twice a day. The drug was acquired at Victory Enterprises®. The placebo was kindly provided by the Universidad de Guadalajara (UdeG), as well as the blinding into two groups: A and B. Enalapril and placebo were packed into bottles without labeling. Clinical assessment included a structured questionnaire to gather demographic and clinical variables as well as determination of CAVI, cfPWV, cIMT, carotid artery distensibility and Einc. The whole set of evaluations were analyzed at the baseline and at the end of 12 weeks of intervention. Results: The CAVI measurement at baseline was 7.1 ± 1.4 and increased up to 7.5 ± 1.2 at the end of 12 weeks. Meanwhile, the enalapril group was as follows: 7.4 ± 1.2 and at the of intervention, reduced to 7.1 ± 0.9. A reduction in delta CAVI of 0.21 in the enalapril intervention group was found. In contrast, an increase of 0.39 was observed in the placebo group. The delta CAVI reduction was not influenced by age or peripheral systolic blood pressure (pSBP). Discussion: Enalapril seems to be effective in CAVI reduction in RA patients. The effect of enalapril intervention on arterial stiffness translated to the clinical context might be interpreted as a reduction of 6.4 years of arterial aging. Trial Registration: The protocol was approved by the Institutional Review Board with the register CI-0117 from UdeG, and 0211/18 from Hospital Civil "Dr. Juan I. Menchaca", SecretarÃa de Salud Jalisco: DGSP/DDI/D.INV.28/18 and retrospectively registered at ClinicalTrials.gov Protocol Registration and Results System: NCT03667131. | |
31661424 | Polyneuropathy and the sural/radial sensory nerve action potential ratio in primary Sjögr | 2020 Jan | Objectives: Polyneuropathy is the most common neurological complication in primary Sjögren's syndrome (pSS). A ratio of sural nerve and superficial radial nerve sensorial action potential amplitudes (SRARs) of <0.4 is an indicator for early axonal neuropathy. We evaluated the polyneuropathies and SRARs in pSS patients.Method: Fifty-two female patients who were diagnosed with pSS according to the European-American Consensus Criteria and 45 healthy controls were enrolled. Nerve conduction studies were performed to diagnose polyneuropathy. Sensory axonal polyneuropathy was diagnosed in three patients, so SRARs were compared in 49 patients and 50 healthy controls.Results: Fifty-two patients with pSS underwent nerve conduction tests. The sural sensory nerve action potential (SNAP) was <6 µV in threepatients and they were diagnosed with sensory axonal neuropathy. SRARs were evaluated in 49 female patients, with a mean age of 51.98 ± 10.79 years and 50 healthy controls with a mean age of 50.52 ± 12.55 years. The mean disease duration was 7.59 ± 6.17 years. The SRAR values were different between the patient and control groups. SRAR was <0.4 in 20.4% of the patient group and <0.4 in 6% of the control group. The SRAR value was not statistically different within the patient group based on anti-Ro and anti-La.Discussion: The potential for neurological involvement in patients with pSS who have no signs or injury should be evaluated because nervous system involvement in pSS is a negative prognostic factor. SRAR in patients with pSS can be used as a marker for the early detection of axonal neuropathy. | |
31327933 | The use of self-retained, cryopreserved amniotic membrane for the treatment of Sjögren sy | 2019 | PURPOSE: To determine whether signs and symptoms of ocular surface disease improve after placement of a self-retained, cryopreserved amniotic membrane (CAM) in patients with Sjögren syndrome (SS). METHODS: The medical records of SS patients who received a self-retained CAM implant (Prokera or Prokera Slim; TissueTech Inc, Doral, FL) for the treatment of ocular surface disease between August 2012 and August 2016 at a single, large academic institution were reviewed retrospectively. Visual acuity, results of slit-lamp examination of the cornea and conjunctiva, and dry eye symptoms, were evaluated before and after CAM insertion. RESULTS: A total of 6 eyes of 6 patients (all female; mean age, 62.5 ± 13.0 years [range, 49-86 years]) were included. All patients were on topical medications at the time of the study and had signs of ocular surface dryness. There were reductions in corneal and/or conjunctival staining in 5 eyes (83%) after the CAM dissolved. All patients who completed therapy (5/5) experienced a relapse in their signs and symptoms within 1 month of removal of the CAM, with an average time to relapse of 24.6 days. Mean follow-up time was 54.5 days. Foreign body sensation and blurred vision were the most common complaints associated with the CAM implant. CONCLUSIONS: In this small case series, self-retained CAM implantation was found to be beneficial in SS patients with ocular surface disease that is refractory to standard therapies; however, we found that the effects were temporary. Future larger studies are needed to confirm these benefits. | |
31249278 | Risk of Cardiovascular Involvement in Patients with Primary Sjögren's Syndrome: a large-s | 2019 Jan | OBJECTIVE: To evaluate the presence of cardiovascular involvement and analyze potential risk factors independently associated with cardiovascular involvement in primary Sjögren's syndrome (PSS) patients. METHODS: We recruited a cohort of 367 PSS patients and 367 age- and gender-matched controls from the First Affiliated Hospital of Wenzhou Medical University. Demographic, clinical and laboratory data, and overt cardiovascular involvement events were recorded. Potential risk factors associated with cardiovascular involvement were determined by multivariate analyses. RESULTS: PSS patients had a significantly higher cardiovascular involvement rate than that of the controls (61.6% versus 29.7%; p<0.01). Compared with PSS patients without cardiovascular involvement, those with cardiovascular involvement were significantly older; had higher rates of hypertension, diabetes, hypoalbuminemia, and hyperlipemia; were more likely to have extraglandular organ involvement; and had a higher level of C-reactive protein (CRP) (all p<0.05). In the multivariate analysis, age, hypertension, and extraglandular organ involvement were found to be risk factors independently correlated with cardiovascular events in PSS patients. CONCLUSIONS: PSS patients are more vulnerable to cardiovascular diseases (CVDs). In addition to traditional CVD risk factors such as age and hypertension, extraglandular organ involvement was found to be independently associated with cardiovascular involvement in PSS patients, which suggests the need for early detection and prevention measures to improve the prognosis in those patients. |