Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
---|---|---|---|---|
34633781 | Upadacitinib. | 2012 | Upadacitinib is an oral selective inhibitor of Janus associated kinase 1 (JAK-1) that is used in the therapy of moderate-to-severe rheumatoid arthritis. Upadacitinib has been associated with a low rate of serum enzyme elevations during therapy, but has not been linked to cases of clinically apparent acute liver injury although it may pose a risk for reactivation of hepatitis B in susceptible patients. | |
31643344 | Baricitinib. | 2012 | Baricitinib is an orally available small molecule inhibitor of Janus kinases that is used to treat moderate-to-severe rheumatoid arthritis and in late 2020 was given emergency use authorization as therapy in combination with remdesivir for severe COVID-19. Baricitinib is associated with transient and usually mild elevations in serum aminotransferase levels during therapy but has yet to be linked to cases of clinically apparent acute liver injury. | |
32798283 | Improvement of Severe Fatigue Following Nuclease Therapy in Patients With Primary Sjögren | 2021 Jan | OBJECTIVE: To assess the safety and efficacy of RSLV-132, an RNase Fc fusion protein, in a phase II randomized, double-blind, placebo-controlled clinical trial in patients with primary Sjögren's syndrome (SS). METHODS: Thirty patients with primary SS were randomized to receive treatment with RSLV-132 or placebo intravenously once per week for 2 weeks, and then every 2 weeks for 12 weeks. Eight patients received placebo and 20 patients received RSLV-132 at a dose of 10 mg/kg. Clinical efficacy measures included the European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index, EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Profile of Fatigue (ProF), and the Digit Symbol Substitution Test (DSST). RESULTS: Patients randomized to receive RSLV-132 experienced clinically meaningful improvements in the ESSPRI score (P = 0.27), FACIT-F score (P = 0.05), ProF score (P = 0.07), and DSST (P = 0.02) from baseline to day 99, whereas patients who received placebo showed no changes in any of these clinical efficacy measures. This improvement was significantly correlated with increased expression of selected interferon-inducible genes (Pearson's correlations, each P < 0.05). CONCLUSION: Administration of RSLV-132 improved severe fatigue, as determined by 4 independent patient-reported measures of fatigue, in patients with primary SS. | |
34325914 | Migraine in multiple sclerosis and other chronic inflammatory diseases. | 2021 Sep | Migraine is a very prevalent disease worldwide and is a major cause of disability. As known for a long time, migraine is associated with neurogenic inflammation. Epidemiological studies have shown that migraine is comorbid with several chronic inflammatory diseases, including multiple sclerosis (MS), chronic inflammatory rheumatic diseases (CIRDs) and inflammatory bowel diseases (IBDs). This brief narrative review highlights some recent data supporting a link between migraine and these three chronic inflammatory diseases. Studies found that migraine prevalence is approximately two-fold higher in these diseases compared to the general population. The causal link between migraine and these chronic inflammatory diseases has not been identified yet. Here, we suggest that systemic mediators (such as cytokines) and gut microbiome make migraine worse or add significant risks. Systemic inflammation biomarkers and gut microbiome modification are certainly avenues worth exploring. | |
34239831 | Recurrent Methotrexate-related Lymphoproliferative Disorder of the Lumbar Spine Origin: A | 2021 Mar | INTRODUCTION: Previously, we reported a relatively rare case of methotrexate-related lymphoproliferative disorder (MTX-LPD) that developed in the lumbar spine. At present, we report the follow-up of that case, presenting with relapse of MTX-LPD. CASE REPORT: The participant was a 75-year-old woman who was diagnosed with MTX-LPD of the lumbar spine and in whom remission was obtained 6 months after discontinuing methotrexate (MTX). At 12 months after remission, elevated levels of soluble interleukin-2 receptor, lymph node swelling on plain computed tomography (CT), and fluorodeoxyglucose uptake on positron emission tomography CT were observed, and recurrent MTX-LPD was diagnosed. Doxorubicin, bleomycin, vinblastine, and dacarbazine therapy was initiated, and partial remission was obtained 6 months later. CONCLUSION: In MTX-LPD, remission is often achieved following discontinuation of MTX alone; however, some patients do not improve, and some patients relapse, as seen in the present case. Such cases are treated using the standard regimen for the observed histologic subtype. Even after remission has been achieved, strict follow-up observation is needed for MTX-LPD. Furthermore, when signs of recurrence are observed during follow-up, practitioners should endeavor to cooperate with other specialists and act without delay. | |
34456485 | Familial cold autoinflammatory syndrome with rheumatoid arthritis. | 2021 Sep | Familial cold autoinflammatory syndrome (FCAS) is a cryopyrin-associated periodic syndrome that presents with episodic fever, skin rash, and joint pain after exposure to cold temperatures. Although the diagnosis is often singular, there are several instances of concurrent underlying autoimmune pathologies with either rheumatoid arthritis (RA) or amyloidosis. Because symptoms of the two entities overlap, it can be difficult to address a potential dual diagnosis of FCAS and an autoimmune disorder. We found seven previously reported cases of FCAS and amyloidosis and five cases of FCAS and RA and present another case of an FCAS-RA dual diagnosis. | |
33333235 | Targeted therapies in interstitial lung disease secondary to systemic autoimmune rheumatic | 2021 Feb | Autoimmune rheumatic diseases (ARD) are characterized by systemic manifestations and multiple organ involvement, including the lung. Interstitial Lung Disease (ILD) is a cardinal manifestation of lung involvement in patients with ARD and is associated with significant morbidity and mortality. Corticosteroids and immunosuppressive drugs are used as first -line treatment. Targeted therapies, such as biological disease modifying antirheumatic drugs (DMARDS) and anti- fibrotic agents are new treatment options. In this review we discuss the role of targeted therapies in patients with ILD secondary to ARD. | |
35018973 | Role of mean platelet volume in differential diagnosis of adult-onset Still's disease and | 2021 Oct | OBJECTIVES: Mean platelet volume is a simple biomarker for inflammatory disease. The purpose of this study is to evaluate the role of mean platelet volume in distinguishing adult-onset Still's disease from sepsis. METHODS: We retrospectively selected 68 patients with adult-onset Still's disease and 55 patients with sepsis between January 2015 and December 2019. Related laboratory data were collected and analyzed. RESULTS: There were no significant differences in white blood cell counts, neutrophils, lymphocytes, and C-reactive protein between adult-onset Still's disease group and sepsis group. However, patients in adult-onset Still's disease group showed higher ferritin and platelets and lower mean platelet volume and platelet distribution width than those in sepsis group (p<0.01 for both). Receiver operating characteristic curve analysis was performed to distinguish adult-onset Still's disease and sepsis. The area under the curve of mean platelet volume was 0.761 (95%CI 0.673-0.849), with a sensitivity of 79.1%, a specificity of 63.3%, and a cutoff value of 10.9 fL. In contrast, the area under the curve of combined ferritin and mean platelet volume was 0.90l (95%CI 0.837-0.965), with higher sensitivity (82.8%) and specificity (96.2%). Therefore, mean platelet volume could be used as a supplementary indicator to distinguish adult-onset Still's disease from sepsis. CONCLUSION: We suggest that mean platelet volume could be used as a supplementary biomarker for differential diagnosis of adult-onset Still's disease and sepsis in addition to ferritin. | |
34161112 | Accuracy of minor salivary gland biopsy in the diagnosis of Sjögren syndrome. | 2021 | OBJECTIVES: The aim of this study was to find out the correlation and evaluate the accuracy of labial minor salivary gland biopsy as a diagnostic tool in the multidisciplinary management of patients with Sjögren syndrome. MATERIALS AND METHODS: Patients, referred to our outpatient office between January 2014 and December 2018 from a rheumatologist for biopsy examination, as part of the complex diagnostic plan for suspected Sjögren syndrome, were included in the current study. Each specimen was examined histomorphometrically by the pathologist to calculate the focus score describing the degree of salivary gland inflammatory infiltration. RESULTS: Fifty patients met the inclusion criteria. From the total number of patients, 39 presented with an established Sjögren syndrome by fulfilling the revised American-European criteria. From those, 27 had a positive lip biopsy. The remaining 12 patients from the total group, who were diagnosed with Sjögren syndrome based on the same criteria, had a negative lip biopsy. CONCLUSION: The labial minor salivary gland biopsy is a valuable diagnostic tool to establish the diagnosis of Sjögren syndrome. However, a positive biopsy result must always be correlated with all the other diagnostic criteria to prove the exact diagnosis (Tab. 1, Fig. 4, Ref. 49). Text in PDF www.elis.sk Keywords: Sjögren syndrome, keratoconjunctivitis sicca, xerostomia, labial minor salivary glands, biopsy, focal lymphocytic infiltration, focus score. | |
32028307 | Accuracy of US Administrative Claims Codes for the Diagnosis of Autoinflammatory Syndromes | 2021 Oct 1 | OBJECTIVE: To determine the accuracy of case definitions for autoinflammatory syndromes (AISs) based on administrative claims codes compared with rheumatology records in the electronic medical record (EMR). METHODS: An AIS screening filter of administrative codes was applied to a large tertiary care EMR database to extract all possible AIS cases. We manually chart reviewed all patients who were evaluated by a rheumatologist to determine their reference standard diagnosis of adult onset Still's disease (AOSD), Behçet's disease (BD), and familial Mediterranean fever (FMF). We calculated sensitivity, specificity, positive predictive values, negative predictive values, and area under the receiver operating characteristic curve of specific codes for diagnosing AIS subtypes. RESULTS: We identified 273 individuals with possible AIS, of which 72 (26.4%) had a true AIS diagnosis, including 24 with AOSD, 32 with BD, and 9 with FMF. For all 3 AIS subtypes, the estimates of specificities and negative predictive values for specific administrative codes were excellent (>95%). Sensitivity estimates were excellent (>89%) for BD and FMF codes and lower for AOSD (46%-50%). Positive predictive values were excellent for BD (>99%) and AOSD (>86%) and lower for FMF (>53%). Area under the receiver operating characteristic curve estimates were excellent for BD (97%-98%) and FMF (93%) and very good for AOSD (75%). CONCLUSIONS: This is the first study to characterize the accuracy of specific administrative codes for the diagnosis of AOSD, BD, and FMF in a large tertiary care EMR. Validation in external EMRs and linked EMR-administrative databases is needed to enable future clinical outcomes research of AIS. | |
32889544 | Genetic and clinical basis for two distinct subtypes of primary Sjögren's syndrome. | 2021 Feb 1 | OBJECTIVES: Clinical presentation of primary Sjögren's syndrome (pSS) varies considerably. A shortage of evidence-based objective markers hinders efficient drug development and most clinical trials have failed to reach primary endpoints. METHODS: We performed a multicentre study to identify patient subgroups based on clinical, immunological and genetic features. Targeted DNA sequencing of 1853 autoimmune-related loci was performed. After quality control, 918 patients with pSS, 1264 controls and 107 045 single nucleotide variants remained for analysis. Replication was performed in 177 patients with pSS and 7672 controls. RESULTS: We found strong signals of association with pSS in the HLA region. Principal component analysis of clinical data distinguished two patient subgroups defined by the presence of SSA/SSB antibodies. We observed an unprecedented high risk of pSS for an association in the HLA-DQA1 locus of odds ratio 6.10 (95% CI: 4.93, 7.54, P=2.2×10-62) in the SSA/SSB-positive subgroup, while absent in the antibody negative group. Three independent signals within the MHC were observed. The two most significant variants in MHC class I and II respectively, identified patients with a higher risk of hypergammaglobulinaemia, leukopenia, anaemia, purpura, major salivary gland swelling and lymphadenopathy. Replication confirmed the association with both MHC class I and II signals confined to SSA/SSB antibody positive pSS. CONCLUSION: Two subgroups of patients with pSS with distinct clinical manifestations can be defined by the presence or absence of SSA/SSB antibodies and genetic markers in the HLA locus. These subgroups should be considered in clinical follow-up, drug development and trial outcomes, for the benefit of both subgroups. | |
34590439 | Association between RA disease activity and periodontitis defined by tooth loss: longitudi | 2021 Sep 30 | OBJECTIVE: To analyze the effect of tooth loss/periodontitis on disease activity in early and established RA. METHODS: Participants of the CAPEA early arthritis cohort reported their number of teeth at baseline. The number of teeth had been validated as predictor of periodontitis. Clinical endpoints including disease activity score (DAS28-ESR), swollen joint count (SJC), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were collected at baseline, 3, 6, 12, 18, and 24 months. We used linear mixed regression models to estimate the association between tooth loss and clinical endpoints over time in early arthritis. For established RA, we analysed cross-sectional data from the German National Database (NDB). All models accounted for age, sex, smoking, seropositivity, education level, and disease duration (only NDB). RESULTS: Among 1,124 CAPEA participants with early arthritis, those with higher tooth loss were older, more often male, smokers, seropositive, and they had higher disease activity and inflammation markers at baseline. Tooth loss was associated with higher disease activity and ESR values over time. Inflammatory markers decreased comparably across tooth loss categories. Glucocorticoid use was higher among those with more tooth loss while dose reduction was similar across tooth loss categories. Among 7,179 NDB participants with longstanding RA, disease activity and inflammation markers but not SJC were significantly higher in patients with more tooth loss. CONCLUSIONS: While we observed an association between tooth loss and disease activity scores and inflammation markers in early and established RA, longitudinal results suggest that tooth loss does not hamper treatment response. | |
33537759 | Disease activity and its predictors in early inflammatory arthritis: findings from a natio | 2021 Oct 2 | OBJECTIVES: We set out to characterize patient factors that predict disease activity during the first year of treatment for early inflammatory arthritis (EIA). METHODS: We used an observational cohort study design, extracting data from a national clinical audit. All NHS organizations providing secondary rheumatology care in England and Wales were eligible to take part, with recruitment from 215/218 (99%) clinical commissioning groups (CCGs)/Health Boards. Participants were >16 years old and newly diagnosed with RA pattern EIA between May 2018 and May 2019. Demographic details collected at baseline included age, gender, ethnicity, work status and postcode, which was converted to an area level measure of socioeconomic position (SEP). Disease activity scores (DAS28) were collected at baseline, three and 12 months follow-up. RESULTS: A total of 7455 participants were included in analyses. Significant levels of CCG/Health board variation could not be robustly identified from mixed effects modelling. Gender and SEP were predictors of low disease activity at baseline, three and 12 months follow-up. Mapping of margins identified a gradient for SEP, whereby those with higher degrees of deprivation had higher disease activity. Black, Asian and Minority Ethnic patients had lower odds of remission at three months follow-up. CONCLUSION: Patient factors (gender, SEP, ethnicity) predict disease activity. The rheumatology community should galvanise to improve access to services for all members of society. More data are required to characterize area level variation in disease activity. | |
34290773 | Diagnostic and therapeutic delay in Rheumatoid Arthritis patients: Impact on disease outco | 2021 Jul | OBJECTIVE: To identify factors causing diagnostic and therapeutic delay in patients with rheumatoid arthritis, and to evaluate relationship of diagnostic and therapeutic delay with disease outcome. METHODS: This cross-sectional study was conducted in Rheumatology Department, Fatima Memorial Hospital, Lahore, Pakistan, from May 2018 to July 2018. In this study 102 patients fulfilling ACR/EULAR criteria 2010 were enrolled. Lag times were calculated in months: lag-1 (delay in initial medical consultation); lag-2 (delay in consulting rheumatologists); lag-3 (diagnostic delay); lag-4 (therapeutic delay). Disease activity and functional outcome were measured by DAS28, HAQ-DI respectively. Association of lag-3 and lag-4 with HAQ-DI and DAS28 was calculated by Pearson correlation. RESULTS: Median (IQR) disease duration of study group was 6(2-10) years. Initial consultations were with; orthopedic surgeon 40(39.2%), general practitioner 27(26.5%), rheumatologist 13(12.7%), medical specialists 14(13.7%). Median (IQR) lag times in months: lag-1 (delayed initial consultation): 2(0-5), lag-2 (delay in consulting rheumatologist): 30(7.7-72), lag-3 (diagnostic delay): 12(3-48), lag-4 (therapeutic delay):18(5.7-72). Factors attributed to lag-3 (diagnostic delay) and lag-4 (therapeutic delay) (p<0.05): older Age (r= 0.2), education level(r= - 0.2), initial consultation (non-rheumatologist) (r=0.2), lag-2(r=0.8), >three doctors visited before diagnosis(r=0.6). Positive anti-CCP antibodies(r=0.2) and lag-1 (delayed initial consultation) (r=1) were associated with lag-3 (diagnostic delay) only; no association was found with positive RA factor. Significant correlation (p=<0.05) of lag-3 (diagnostic delay) was found with both DAS28(r=0.2) & HAQ-DI(r=0.2). Similarly lag-4 (therapeutic delay) also correlated with both & DAS28(r=0.2) & HAQ-DI(r=0.3) (p=<0.05). CONCLUSION: Diagnostic and therapeutic delay were associated with older age, lower education and delayed consultation with rheumatologist but not with positive RA factor. Positive anti-CCP antibodies were associated with diagnostic delay only. Diagnostic and therapeutic delay led to high disease activity and poor functional outcome in RA patients. | |
34168509 | Objective and Subjective Sleep in Rheumatoid Arthritis and Severe Seasonal Allergy: Prelim | 2021 | INTRODUCTION: Disturbed sleep in inflammatory disorders such as allergy and rheumatoid arthritis (RA) is common and may be directly or indirectly related to disease processes, but has not been well characterized in these patient groups, especially not with objective methods. AIM: The present study aimed to characterize objective and subjective sleep in patients with allergy or RA using sleep diaries, one-channel EEG and actigraphy. It also aimed to investigate if sleep measures were associated with central immune activation, assessed using translocator protein (TSPO) positron emission tomography, as well as cytokine markers of peripheral inflammation and disease-specific symptoms or general symptoms of sickness. METHODS: In total, 18 patients with seasonal pollen allergy, 18 patients with RA and 26 healthy controls were included in the study. Allergy patients and matched controls were assessed twice, in and out of pollen season, and RA patients and controls were assessed once. Sleep was recorded for approximately 1 week at each occasion. RESULTS: Patients with allergy had increased levels of slow-wave sleep during pollen season. In contrast, patients with RA had less SWS compared to healthy controls, while no differences were observed in sleep duration or subjective sleep quality. Across groups, neither proinflammatory cytokines, grey matter TSPO levels nor general sickness symptoms were associated with objective or subjective measures of sleep. Rhinitis, but not conjunctivitis, was correlated to worse subjective sleep and more slow wave sleep in allergy. Functional status, but not disease activity, predicted lower subjective sleep in RA. CONCLUSION: This study tentatively indicates that both patients with allergy and RA display sleep alterations but does not support inflammation as an independent predictor of the sleep disturbance across these patient groups. | |
33976574 | High Prevalence of Depressive Symptoms Among Ugandan Patients with Rheumatoid Arthritis. | 2021 | BACKGROUND: There is a scarcity of data on the burden of depression among Ugandans with rheumatoid arthritis (RA) patients. We aimed to screen for symptoms of depression, their severity and associated factors among patients with RA in Uganda. PATIENTS AND METHODS: A descriptive, cross-sectional study was conducted between September and December 2020 at Mulago National Referral Hospital (MNRH) and Nsambya Hospital. Patients with RA were enrolled consecutively. Data on demographics, disease course and comorbidities and depression symptomatology were collected through an interviewer administered questionnaire. Symptoms of depression were screened for using the depression/anxiety dimension of the EuroQoL questionnaire. RESULTS: Forty-eight patients with a median age of 52 (IQR: 43.5-60.5) years were recruited in the study. The majority of the patients were female (91.7%, n=44). Twenty-nine patients (60.4%) had comorbidities with a median Charlson comorbidity score of 3 (IQR: 2-4). Overall, 70.8% (n=34) had depressive symptoms. Patients attending MNRH were more likely to have depressive symptoms (p=0.025). Significantly, patients with depressive symptoms were younger (p=0.027), had lower health index value (p<0.001), and lower overall self-reported health status (p=0.013). At binary logistic regression, patients at MNRH (crude odds ratio (COR): 4.32, 95% confidence interval (CI): 1.16-16.15, P=0.030), patients aged <52 years (COR: 5.24, 95% CI: 1.23-22.28, P=0.025) and those with mild RA (COR: 5.71, 95% CI: 1.15-28.35, P=0.033) were significantly more likely to have depressive symptoms. Increase in age (COR: 0.94, 95% CI: 0.89-0.99, P=0.025), and high visual analogue score (COR: 0.94, 95% CI: 0.89-0.99, P=0.013) were protective. CONCLUSION: Depressive symptoms were common among RA patients in Uganda. Routine screening, diagnosis and management of depression is recommended among young patients to improve quality of life and patient outcomes. | |
33656739 | Safety and Effectiveness of Peficitinib (ASP015K) in Patients with Rheumatoid Arthritis: F | 2021 Mar | INTRODUCTION: This final analysis of a long-term extension (LTE) study assessed the safety, tolerability, and effectiveness of peficitinib (ASP015K), a pan-Janus kinase inhibitor, in Asian patients with rheumatoid arthritis (RA). METHODS: Patients had previously completed the 12-week phase 2b (RAJ1), or 52-week phase 3 (RAJ3 and RAJ4) peficitinib studies in Japan, Korea, and Taiwan, and received oral peficitinib 50 or 100Â mg/day. Dose increase to 150Â mg/day or reduction to 50Â mg/day was permitted. Efficacy endpoints included American College of Rheumatology (ACR)20/50/70 response rates, 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP), and ACR components. Safety endpoints included treatment-emergent adverse events (TEAEs), and incidence rates (IRs) of adverse events of special interest per 100 patient-years (PY). RESULTS: Overall, 843 patients received peficitinib for a mean 32.0Â months (maximum 85.2Â months), and most (64.4%) received peficitinib 100Â mg/day as a maximum dose. Respective ACR20/50/70 response rates were maintained from baseline (week 0 of LTE; 71.6, 52.1, and 34.7%) to end of treatment (78.7, 63.3, and 44.1%); continuous improvements in ACR components and DAS28-CRP were observed from the baselines of preceding studies and throughout the LTE. Overall, 796/843 (94.4%) patients experienced TEAEs; most were severity grade 1/2. Most common TEAEs were nasopharyngitis (47.0%) and herpes zoster (17.3%). Drug-related TEAEs leading to permanent discontinuation occurred in 140 (16.6%) patients, and IRs (95% confidence interval) per 100 PY of serious infections, herpes zoster-related disease, and malignancies were 2.7 (2.1, 3.4), 7.3 (6.2, 8.6), and 1.2 (0.9, 1.8), respectively. Two deaths occurred during the study; one each from diffuse large B cell lymphoma and pneumonia, which were, respectively considered probably and possibly related to study drug. CONCLUSIONS: Improvements in effectiveness variables were maintained during this long-term study of peficitinib in Asian patients with RA; peficitinib was generally well tolerated over a mean 32Â months' duration. TRIAL REGISTRATION: ClinicalTrials.gov. NCT01638013, retrospectively registered on 11 July 2012 https://clinicaltrials.gov/ct2/show/NCT01638013 . | |
33401700 | Insights in the Role of Lipids, Oxidative Stress and Inflammation in Rheumatoid Arthritis | 2021 Jan 2 | Rheumatoid arthritis (RA) is a highly debilitating chronic inflammatory autoimmune disease most prevalent in women. The true etiology of this disease is complex, multifactorial, and is yet to be completely elucidated. However, oxidative stress and lipid peroxidation are associated with the development and pathogenesis of RA. In this case, oxidative damage biomarkers have been found to be significantly higher in RA patients, associated with the oxidation of biomolecules and the stimulation of inflammatory responses. Lipid peroxidation is one of the major consequences of oxidative stress, with the formation of deleterious lipid hydroperoxides and electrophilic reactive lipid species. Additionally, changes in the lipoprotein profile seem to be common in RA, contributing to cardiovascular diseases and a chronic inflammatory environment. Nevertheless, changes in the lipid profile at a molecular level in RA are still poorly understood. Therefore, the goal of this review was to gather all the information regarding lipid alterations in RA analyzed by mass spectrometry. Studies on the variation of lipid profile in RA using lipidomics showed that fatty acid and phospholipid metabolisms, especially in phosphatidylcholine and phosphatidylethanolamine, are affected in this disease. These promising results could lead to the discovery of new diagnostic lipid biomarkers for early diagnosis of RA and targets for personalized medicine. | |
33772564 | Stimulated whole salivary flow rate: The most appropriate technique for assessing salivary | 2021 May 1 | BACKGROUND: We sought to determine the most appropriate method for measuring salivary flow to aid the diagnosis of Sjögren's syndrome (SS). Specifically, we compared the unstimulated whole salivary flow rate (UWSFR) with the stimulated whole salivary flow rate (SWSFR). MATERIAL AND METHODS: This case-control study comprised one group of 103 patients with SS and a control group of 50 healthy people. We measured the UWSFR and SWSFR in both groups according to the guidelines established by Navacet [1993]. RESULTS: The UWSFR and SWSFR were significantly lower in the patient group compared with the controls (p < 0.01). Among the participants in the patient group, we found a decreased UWSFR in 84 individuals (81.5%) and a decreased SWSFR in 90 individuals (87.4%). We encountered difficulties obtaining saliva in 37 (35.9%) patients during the UWSFR test, and in 12 (11.7%) patients during the SWSFR test. There was no significant statistical difference in the UWSFR or SWSFR between patients with primary and secondary SS. CONCLUSIONS: Compared with the UWSFR, the SWSFR is a more suitable and effective method for measuring salivary flow in patients with SS, as well as for qualitative analysis of the obtained saliva. | |
34207385 | Influence of the FCGR2A rs1801274 and FCGR3A rs396991 Polymorphisms on Response to Abatace | 2021 Jun 18 | Abatacept (ABA) is an immunosuppressant indicated for treatment of rheumatoid arthritis (RA). Effectiveness might be influenced by clinical RA variants and single-nucleotide polymorphisms (SNPs) in genes encoding protein FCGR2A (His131Arg) and FCGR3A (Phe158Val) involved in pharmacokinetics of ABA. An observational cohort study was conducted in 120 RA Caucasian patients treated with ABA for 6 and 12 months. Patients with the FCGR2A rs1801274-AA genotype (FCGR2A-p.131His) showed a better EULAR response (OR = 2.43; 95% CI = 1.01-5.92) at 12 months and low disease activity (LDA) at 6 months (OR = 3.16; 95% CI = 1.19-8.66) and 12 months (OR = 6.62; 95% CI = 1.25-46.89) of treatment with ABA. A tendency was observed towards an association between the FCGR3A rs396991-A allele (FCGR3A-p.158Phe) and better therapeutic response to ABA after 12 months of treatment (p = 0.078). Moreover, we found a significant association between the low-affinity FCGR2A/FCGR3A haplotypes variable and LDA after 12 months of ABA treatment (OR = 1.59; 95% CI = 1.01-2.58). The clinical variables associated with better response to ABA were lower age at starting ABA (OR = 1.06; 95% CI = 1.02-1.11) and greater duration of ABA treatment (OR = 1.02; 95% CI = 1.01-1.04), lower duration of previous biological therapies (OR = 0.99; 95% CI = 0.98-0.99), non-administration of concomitant disease-modifying antirheumatic drugs (DMARDs) (OR = 24.53; 95% CI = 3.46-523.80), non-use of concomitant glucocorticoids (OR = 0.12; 95% CI = 0.02-0.47), monotherapy (OR = 19.22; 95% CI = 2.05-343.00), lower initial patient's visual analogue scale (PVAS) value (OR = 0.95; 95% CI = 0.92-0.97), and lower baseline ESR (OR = 0.92; 95% CI = 0.87-0.97). This study showed that high-affinity FCGR2A-p.131His variant, low-affinity FCGR3A-p.158Phe variant, and combined use of FCGR2A/FCGR3A genetic variations could affect ABA effectiveness. Further studies will be required to confirm these results. |