Symposium on Gout and Gout
Author link opens overlay panel,,,,,,,,
https://doi.org/10.1016/j.semarthrit.2022.152052access to rights and content
To determine whether some patients who tested positive for anti-Scl-70 antibodies in clinical practice but did not have classifiable systemic sclerosis tested negative for anti-Scl-70 antibodies using a more specific immunodiffusion assay.
Patients evaluated by a rheumatologist at a scleroderma referral center who tested positive for anti-Scl-70 antibodies before referral but did not have SSc classifiable by clinical criteria were invited to immunodiffusion testing for anti-Scl-70 antibodies. . Record the patient's demographic and clinical characteristics at the time of evaluation and review the results of diagnostic tests using medical records.
Fifty-two patients were recruited during the 8-year period, of whom 48 (92.3%) were negative and 4 (7.7%) were positive for anti-Scl-70 antibodies by immunodiffusion. Of the 48 negative patients, 18 (37.5%) were negative by ANA indirect immunofluorescence, 33 (68.8%) did not present Raynaud's phenomenon, and 43 (89.6%) were classified according to the 2013 ACR/clinical standard point. ≤ 1 EULAR SSc. 21 (43.8%) patients with negative anti-Scl-70 antibodies by immunodiffusion underwent chest CT and 14 (29.2%) echocardiography. A total of 23 patients had at least one outpatient follow-up. Three of the four patients who were immunodiffusion-positive for anti-Scl-70 antibodies, but none of the 19 patients who were immunodiffusion-negative, developed sufficient criteria during follow-up to be classified as SSc.
Detection of anti-Scl-70 antibodies in commercial laboratories commonly used in clinical practice can give false positive results. These findings can cause patient anxiety, as well as unnecessary referrals and diagnostic evaluations.
Systemic sclerosis (SSc) is an autoimmune disease with a heterogeneous clinical presentation . Detection of autoantibodies is widely used to aid in the diagnosis of SSc and also has prognostic significance . Anti-Scl-70 antibodies (also known as anti-topoisomerase I antibodies), one of three autoantibodies included in the 2013 ACR/EULAR SSc classification criteria , have been shown to be specific for SSc and predict the risk of diffuse skin involvement, progressive interstitial lung disease (PID) and mortality , , , , , , , , .
Anti-Scl-70 antibodies in SSc patients were first described in 1979 when some antibodies from SSc patients were found to react with 70 Dalton protein purified from rat hepatocyte nuclei . The Scl-70 antigen (originally named based on its molecular weight) was later identified as a soluble proteolytic product of DNA topoisomerase I , , . Scl-70 antigen can be enriched from rabbit or calf thymus and used as a measure for the detection of anti-Scl-70 antibodies in serum samples by passive immunodiffusion [14,17]. In addition to immunodiffusion, several alternative methods for the detection of anti-Scl-70 antibodies have been described. These include enzyme-linked immunosorbent assay (ELISA) (sometimes called enzyme immunoassay or EIA), Western blotting, countercurrent immunoelectrophoresis (CIE), immunoprecipitation, chemiluminescence immunoassay (CIA), line blot immunoassay (LIA), and the use fluorescent staining antigen. . microspheres (sometimes called multiplex bead assays or multiplex bead assays) [5,14,,,,,,,]] . Adding another possible source of variation, recombinant topoisomerase I protein can be used as a target for the detection of anti-Scl-70 antibodies instead of native topoisomerase I enriched from rabbit or calf thymus .
Practicing physicians rely on local or commercial hospital or clinic laboratories for autoantibody testing, including anti-Scl-70 antibody testing. However, it is unclear to what extent the anti-Scl-70 antibody assay used by each laboratory for diagnostic evaluation of SSc has been validated. A recent report based on data from an academic laboratory showed that detection of anti-Scl-70 antibodies by multiplex flow immunoassays was poorly specific for SSc . ELISA shows better specificity than multiplex flow immunoassays, but much worse than immunodiffusion. The low specificity of the multiplex flow immunoassay and ELISA, two assay formats commonly offered by commercial laboratories in the United States, for testing for anti-Scl-70 antibodies raises concerns that false positive results for anti-Scl-70 antibodies may be frequent in the clinic. practice. Here, we present a case series to test this concern by identifying patients who tested positive for anti-Scl-70 antibodies in a commercial or local laboratory but did not have SSc and tested negative for anti-Scl-70 antibodies on immunodiffusion.
The patient visited the University of Texas Rheumatology Clinic at Houston Health Science Center (UTHSC)H), and evaluated by one of four rheumatologists (SA, BJ, MDM, or BS). Patients will be invited to participate in this study if: (1) they were positive for anti-Scl-70 antibodies in a commercial or local laboratory before evaluation in our clinic and (2) they did not have sufficient clinical criteria in our time.
A total of 52 patients were enrolled over an 8-year period from 2013 to 2021. Immunodiffusion testing for anti-Scl-70 antibodies was negative in 48 patients and positive in 4 patients. An example of anti-Scl-70 antibody test results is shown in Figure 1.
In this study, we identified 48 patients who tested positive for anti-Scl-70 antibodies at a commercial or local laboratory but did not have SSc and who tested negative for anti-Scl-70 antibodies by immunodiffusion. Many of these patients did not have clinical criteria for SSc and/or were ANA negative by indirect immunofluorescence. We concluded that some anti-Scl-70 antibody results from laboratories commonly used in clinical practice were false positive.
in the most recent
This case series highlights the propensity of anti-Scl-70 antibody tests widely used in clinical practice to produce false-positive results, as well as some of their potential negative consequences. We suggest that the use of an anti-Scl-70 antibody immunodiffusion test in clinical practice will directly benefit clinicians and patients.
APPENDIX A: INDIVIDUAL PATIENT FACT SHEET
APPENDIX B: LINKS TO COMPANY WEBSITES AND INFORMATION ABOUT ITS METHODS
CRediT Author Contribution Statement
Brian H. Lin:Data curation, formal analysis, research, methodology, writing - manuscript.Shelvin Assassi:Conceptualization, Formal analysis, Fundraising, Research, Methodology, Project administration, Supervision, Writing - review and edition.Julio Carlos:Data curation, formal analysis, research, methodology, writing: review and editing.rana:Data curation, Writing - review and editing.Malka A. Lyons:Data curation, Writing - review and editing.Bohra
Declaration of conflicting interests
SA has received grants from the National Institutes of Health, Department of Defense, Scleroderma Research Foundation, Momenta, Boehringer Ingelheim, and Janssen, and from Boehringer Ingelheim, Corbus, Novartis, CSL Behring, Abbvie, and AstraZeneca Consulting Fees, Integrity CE, and the North Carolina Rheumatology Association, and served as a pro bono volunteer with the Scleroderma Clinical Trials Consortium and the Scleroderma Foundation Medical Advisory Board. MDM has
We thank Drs. Sam Theodore and Dr. Pat Gonzales for their assistance with patient recruitment, blood sampling, and access to external medical records, and Hau Pham and Kenneth Pham for their assistance in the laboratory.
SA received fromNational Institutes of Health(RO1AR073284BS was supported by a grant from the Arthritis National Research Foundation.
- GRAMS.spencer verdesale.
Test performance in systemic sclerosis: anti-centromere and anti-Scl-70 antibodies
american journal of medicine
African-American race and topoisomerase I antibodies are associated with greater severity of scleroderma lung disease
- J. P.Ioannidissale.
Mortality in systemic sclerosis: an international meta-analysis of individual patient data.
american journal of medicine
Identification of the nucleoprotein (Scl-70) as a unique target of human antinuclear antibodies in scleroderma
Topoisomerase I (Scl-70) autoantibodies: analysis by gel diffusion, Western blot and ELISA
Serum Prediffusion Convective Immunoelectrophoresis: An Improved Method for the Detection and Characterization of Antibodies Against Extractable Nuclear and Cytoplasmic Antigens
- keep timehome
Scleroderma: role of serum autoantibodies in defining specific clinical phenotypes and organ system involvement
Curr Opin Rheumatologists
- F.from abovesale.
Systemic Sclerosis Classification Criteria 2013: A Collaborative Initiative of the American College of Rheumatology/European League Against Rheumatism
- VENEREAL DISEASE.Steensale.
Clinical relevance and prognosis based on serum autoantibodies in patients with systemic sclerosis
rhubarb for arthritis
Clinical and prognostic associations based on serum antinuclear antibodies in Japanese patients with systemic sclerosis
rhubarb for arthritis
Effects of clinical features, serum antinuclear antibodies, and lung function on survival in patients with systemic sclerosis
Journal of Rheumatology
Predictors of interstitial lung disease in early systemic sclerosis: longitudinal prospective study of the GENISOS cohort
Development of an outcome-based disease classification in systemic sclerosis using autoantibodies and skin subgroups
Autoreactive B cell responses to nuclear antigens in systemic sclerosis: implications for disease pathogenesis
2023, Gout and Gout Symposium
Autoantibody reactivity allows stratification of patients early in the disease course, facilitating a personalized approach and treatment [66,85,92]. When considering the prognostic significance of ATA in particular, it is important to take into account the variability in ATA results due to differences in test methods [93,94]. The strong association with SSc and its role as a biomarker may indicate the potential pathogenicity of these autoreactive B-cell responses, similar to those reported for SLE , antiphospholipid syndrome , and Sjogren's syndrome .
A hallmark of the pathogenesis of systemic sclerosis (SSc) disease is the presence of an autoreactive B cell response directed against nuclear proteins. Almost all patients with SSc have circulating antinuclear autoantibodies, among which anti-topoisomerase 1, anti-centromeric protein, anti-RNA polymerase III, and anti-fibrin autoantibodies (ATA, ACA, ARA, and AFA, respectively) are the most common. and specific. In clinical practice, autoantibodies are used as diagnostic biomarkers that can help identify the clinical phenotype of the disease. However, the drivers of disease progression in SSc are still poorly understood, and it is difficult to predict the course of the disease in individual patients. Furthermore, treatment decisions are still quite empirical and response rates vary between clinical trials due to patient heterogeneity. Current evidence suggests that certain patients may benefit from B cell-directed therapy. Therefore, it is important to understand the role of antinuclear autoantibodies and their underlying B cell responses in the pathogenesis of SSc.
The problem of the low specificity of the detection of anti-Scl-70 antibodies in commercial laboratories
2022, Arthritis and Gout Symposium
Sex-specific risk of anti-topoisomerase antibodies for mortality and disease severity in systemic sclerosis: a 10-year analysis of the Leiden CCISS and EUSTAR cohorts
2022, The Lancet Rheumatology
The presence of other unknown or unmeasured autoantibodies in these at-risk populations cannot be excluded, but is unlikely to have influenced the results, given the rarity of simultaneous expression of different autoantibodies in patients with systemic sclerosis. We also cannot rule out that some people may have false positive results on the ATA test. 33 However, as all patients in this study were ANA positive and had a clinical diagnosis of systemic sclerosis, we believe that our results were not due to false positive ATA results.
Our objective was to assess the sex-specific risk of anti-topoisomerase I (ATA) antibodies for mortality in patients with systemic sclerosis, diffuse cutaneous systemic sclerosis, interstitial lung disease, and pulmonary hypertension in two groups.
The study was a 10-year analysis of the prospective Combined Care Leiden Systemic Sclerosis (CCISS) cohort in the Netherlands and the European International Scleroderma Trial and Research (EUSTAR) cohort. Patients with systemic sclerosis according to the 2013 American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) classification were included; available autoantibody status; available skin subtype; at least one available stromal imaging evaluation of lung disease; and a known start date. Patients with systemic sclerosis were divided into six risk groups by gender and autoantibody status (anti-centromeric antibody [ACA] positive women, ACA positive men, ACA and ATA negative women, ACA and ATA negative men, ATA negative women). positive and ATA positive men). We constructed Kaplan-Meier curves and Cox proportional hazards models considering left-truncated survival to avoid bias, since all patients had a disease onset date (first non-Raynaud's symptom) prior to the date of admission. to the cohort. The primary outcome was all-cause mortality, and the secondary outcomes were diffuse cutaneous systemic sclerosis, interstitial lung disease, and pulmonary hypertension.
445 (63%) of 708 participants in CCISS between April 1, 2009 and January 1, 2022 (101 [23%] men and 344 [77%] women) and June 2004 4,263 (50%) of 8,590 for 1 day and on March 28, 2018 in EUSTAR (783 [18%] men and 3480 [82%] women) were eligible for this study. In both cohorts, ATA expression was significantly more common in men than in women (39 [39%] of 101 men vs. 67 [19%] of 344 women in CCISS; p<0 0001 and 381 [49%] of 783 men vs. .1323 [38%] of 3480 women in EUSTAR; p<0 0001). Based on estimated survival, within 10 years, 30% of ATA-positive men and 12% of ATA-positive women died in the CCISS cohort and 33% and 15%, respectively, in the CCISS cohort. of EUSTAR. After adjustment for age, race, and autoantibody status, male gender remained the most important risk factor for all-cause mortality (HR 2 9 [95% CI 1 5-5 5] in CCISS, p=0 0018; EUSTAR HR 2 6 [2.0 -3.4] inches, p<0.0001).
We show that the association between male gender and increased mortality in systemic sclerosis cannot be explained by a higher incidence of ATA. However, more research is needed on the impact of gender characteristics in people with systemic sclerosis.
The role of scleroderma autoantibodies in guiding surveillance and treatment decisions
2022, the latest opinion in rheumatology
Early diagnosis of systemic sclerosis: deciphering the heterogeneity of systemic sclerosis in the early stages of the disease
2022, Journal of Scleroderma and Related Disorders
Pediatric Glucocorticoid Toxicity Index
Arthritis and Rheumatology Symposium, bind 56, 2022, artikel 152068
Develop the pediatric glucocorticoid toxicity index (pGTI), an assessment of standardized weighted clinical outcomes to measure changes in glucocorticoid (GC) toxicity over time.
Fourteen medical specialists from seven subspecialties attended the meeting. Specialist physicians represent several subspecialties, of which GC plays an important role in the treatment of inflammatory diseases: nephrology, rheumatology, oncology, endocrinology, genetics, psychiatry, and maternal-fetal medicine. Nine researchers are from Canada, Europe, or New Zealand, and five are from the United States. Group consensus methods and multicriteria decision analysis were used. The pGTI is a comprehensive assessment of common, important, and dynamic GC toxicity. These toxicities were categorized as minor, moderate, or major health domains and weighted by severity. Relative weights are derived from group consensus and multi-criteria decision analysis using 1000MindsMT valuesoftware platform Two quantitative scores comprise the overall toxicity profile derived from the pGTI data: (1) cumulative deterioration score, (2) composite improvement score. The pGTI also includes an unweighted qualitative record of GC side effects, called the Impairment Checklist, which documents less common toxicities that, while potentially serious, are unlikely to change with GC dose.
One hundred seven (107) toxic items are included in the pGTI and thirty-two (32) toxic items are included in the damage list. To assess how well the pGTIs corresponded with expert clinical judgment, the investigators ranked the 15 cases based on clinical judgment from highest to lowest GC toxicity. The expert ratings were then compared with the pGTI case ratings, yielding excellent agreement (weighted kappa 0.86). The pGTI was migrated to the digital environment after its development and initial validation. The digital platform is designed to ensure ease of clinical use, rigor of application, and accuracy of scoring. Clinic staff enter vital signs, laboratory results, and medication changes against the pGTI score. Clinicians document findings of GC myopathy, skin toxicity, mood disturbances, and infection. The pGTI algorithm then applies weights to this raw data and calculates a score. Built-in logic explains the impact of age- and gender-related reference intervals on several domains of health: blood pressure, lipid metabolism, and bone mineral density. Other algorithms account for expected changes in height Z scores used in growth domains, thus addressing issues specific to GC toxicity in children. The impairment checklist provides a comprehensive measure of GC toxicity, but does not affect the pGTI score, as the scoring fields emphasize manifestations of GC toxicity that may change over the course of the assay.
We describe the development and initial evaluation of a weighted composite toxicity index to assess the morbidity associated with GC use in children and adolescents. The development of the pGTI digital platform was essential to perform the detailed calculations required to ensure rigor, precision, and ease of use in clinical and research settings.
COVID-19 outcomes in patients with dermatomyositis: a registry-based cohort analysis
Symposium on Arthritis and Rheumatism, bind 56, 2022, artikel 152034
Background: It is well known that patients with rheumatic diseases (RD) such as DM are susceptible to various types of infections because the aggressive activity of the disease requires high doses of immunosuppressive therapy. Due to the heterogeneity of the disease, the severity of COVID-19 in ER has been limited in the literature. Therefore, the specific details of mortality are essential to understand the necessary precautions in treatment.
Objective: To determine the outcome of COVID-19 in DM compared to controls and to identify risk associations by sex, race, interstitial lung disease, tumors, and use of immunosuppressants.
Methods: Retrospective data on people with DM and COVID-19 and the general population with COVID-19 between January 2020 and August 2021 were retrieved from the TriNetX database. 1:1 propensity score matching was used to adjust for confounding factors. We assessed COVID-19 outcomes such as mortality, hospitalization, ICU admission, severe COVID-19, mechanical ventilation (MV), acute kidney injury (AKI), venous thromboembolism (VTE), ischemic stroke, acute respiratory distress syndrome (ARDS), renal replacement therapy (RTR) and sepsis. Subgroup analyzes included gender, race, ILD, cancer patients, disease-modifying antirheumatic drug (DMARD) use, and glucocorticoid (GC) use.
RESULTS: We identified 5,574 diabetic patients with COVID-19 and 5,574 general population (control groups) with COVID-19. DM with COVID-19 had lower risk of death compared with controls [RR 0.76], hospitalization [RR 0.8], severe COVID-19 [RR 0.76], AKI [RR 0.83] and sepsis [RR 0.73]. Men and African Americans were more likely to develop AKI [RR 1.35, 1.65], whereas African Americans were more likely to have severe COVID-19 [RR 1.62] and VTE [RR 1.54]. DMs in the EPI group also experienced higher odds of severe COVID-19 infection [RR 1.64] and VTE [RR 2.06].
DM patients treated with DMARDs and corticosteroids had higher odds of hospitalization [RR 1.46, 2.12] and sepsis [RR 3.25, 2.4] Subgroup analysis of DM patients with COVID-19 with a 5-year history of cancer was insufficient for a significant significant comparison .
Conclusions: Patients with dermatomyositis without comorbidity had reasonable COVID-19 outcomes, including mortality and hospitalization. Black race, male gender, ILD, DMARDS, and corticosteroid users were associated with worse outcomes.
Rheumatic diseases in patients with fever of unknown origin: systematic review and meta-analysis
Arthritis and Rheumatology Symposium, bind 56, 2022, artikel 152066
A systematic review of the literature and meta-analysis was performed to estimate the proportion of cases of fever of unknown origin (FUO) and inflammation of unknown origin (UIO) due to rheumatic diseases and the relative frequency of specific entities associated with FUO/UIO.
PubMed and EMBASE were searched between January 1, 2002 and December 31, 2021 for studies containing ≥50 patients reporting an FUO/IUO aetiology. The primary outcome was the proportion of FUO/IUO patients with rheumatic disease. Secondary outcomes included associations between study and patient characteristics and the proportion of rheumatic disease and the relative frequency of rheumatic disease in this group. Proportion estimates were calculated using a random effects model.
The included studies represented 16,884 patients with FUO/IUO. Rheumatic diseases explained 22.2% (95% CI 19.6 – 25.0%) of the cases. Adult Still's disease (22.8% [95% CI 18.4-27.9%]), giant cell arteritis (11.4% [95% CI 8.0-16.3%), and lupus erythematosus systemic (11.1% [95% CI 9.0-13.8]%]) was the most common disease. Rheumatic diseases were significantly more prevalent in high-income countries (25.9% [95% CI 21.5 – 30.8%)] than in middle-income countries (19.5% [95% CI 16.7 – 22.7%) and in prospective studies (27.0) High % [95% CI 21.9–32.8%]) compared to retrospective studies (20.6% [95% CI 18.1–24, 0%]). Multivariable meta-regression analysis showed that rheumatic disease was associated with duration of fever (0.011 [95% CI 0.003-0.021]; P=0.01) and the proportion of patients with OIU (1.05 [95% CI 0.41-1.68], P= 0.002).
Rheumatic diseases are common causes of FUO/IUO. Treatment of patients with FUO/IUO should be supervised by physicians familiar with the diagnosis of rheumatology.
Factors Influencing Patient-Reported Outcomes in ANCA-Associated Vasculitis: The Relevance of Patient Global Assessment
Symposium on arthritis and rheumatism, link 56, 2022, article 152048
Patient-reported outcomes (PROs) are currently poorly integrated into the clinical assessment of disease activity in patients with ANCA-associated vasculitis (AAV).
To assess the distribution of Patient Global Assessment (PtGA) in AAV patients in stable remission and determine the PtGA correlation; to assess inconsistency between PtGA and Physician Global Assessment (PhGA) scores.
Patients diagnosed with AAV who were in stable remission (BVAS = 0) and Physician's Global Assessment (PhGA) = 0 were included. The following PROs were assessed on a visual analogue scale (VAS) from 0 to 100 based on patient opinion: PtGA , fatigue, pain, general health, sleep quality and chronic deterioration. The Cragg Hurdle model was used to evaluate predictors of PtGA.
65 patients were included, 57% women, mean age 61±12 years. Median duration of the disease 6 years (IQR 3-12). The vasculitic lesion index (VDI) was 4.4±2.3. Despite being classified as in remission, 37% of the patients had elevated PtGA. PtGA was not associated with age, comorbidities, educational level, type of AAV diagnosis, number of organ systems affected, previous relapse, disease duration, or greater VDI. Female gender was significantly associated with PtGA: 51% of female patients reported elevated PtGA compared to 18% of men (p=0.009). PtGA was significantly associated with all other PROs tested. Pain and fatigue are the main determinants of elevated PtGA.
A large proportion of AAV patients who are considered by clinicians to be in remission still report ongoing uncontrolled disease. PtGA is markedly affected by pain and fatigue, and more emphasis should be placed on this in future evaluations of AAV patients.
Efficacy of plasmapheresis in addition to standard immunosuppressive therapy in adults with macrophage activation syndrome associated with autoimmune inflammatory rheumatic disease, a single-center real-world analysis
Arthritis and Rheumatology Symposium, bind 55, 2022, artikel 152043
There is currently a lack of real evidence on the effectiveness of treatments for macrophage activation syndrome (MAS) in adults associated with autoimmune inflammatory rheumatic disease (AIIRD).
To analyze the effectiveness of different treatment methods, especially plasma exchange (PE) in MAS associated with AIIRD.
Among the 5775 AIIRD patients at Tongji Hospital from 2014 to 2020, a total of 62 AIIRD-related MAS cases were collected. Clinical features and potential factors associated with prognosis were characterized using unadjusted logistic regression, operator selection and absolute minimum shrinkage (LASSO), and inverse probability of treatment weights (IPTW) analysis. Paired t-test was used to compare changes in inflammatory indicators before and after PE treatment.
Baseline data were defined as data collected at the start of the MAS, and all 62 patients were diagnosed with AIIRD before the start of the MAS. The prevalence of MAS in the AIIRD was 1.1%, and the most common types of AIIRD were systemic lupus erythematosus (45.2%) and adult Still's disease (33.9%). The 62 patients with MAS were treated with corticosteroids, 87.1% received at least one immunosuppressive agent, and 54.8% received PE. LASSO regression indicated positive effects of PE-based variables. After PE treatment, the serum levels of several inflammatory cytokines decreased rapidly, accompanied by improvements in clinical symptoms and laboratory indicators, including ferritin, lactate dehydrogenase, and C-reactive protein. LASSO regression showed that PE treatment was associated with a significant reduction in mortality (from 53.6% to 11.8%) with a hazard ratio (HR) of 0.148 (p<0.001) after adjustment for confounding factors using IPTW analysis.
With background therapy of glucocorticoids and immunosuppressants, PE is an effective method of rapidly clearing inflammatory cytokines and reducing AIIRD-associated MAS mortality.
This study provides real information on the efficacy of PE in AIIRD-associated MAS.
Hydroxyquinone use does not increase the risk of venous thromboembolism in patients with rheumatoid arthritis: real-world evidence from a population-based cohort study
Arthritis and Rheumatology Symposium, bind 56, 2022, artikel 152044
© 2022 The Elsevier Company. All rights reserved.