Association between toxic organochlorine levels in human serum and systemic lupus erythematosus

Organochlorines (OCs) are groups of highly toxic pesticides with known immunotoxicity. The present work aimed to study the potential association between serum residues of OCs and the risk of developing systemic lupus erythematosus (SLE) as well as correlating to the clinical-laboratory manifestations in a sample of Egyptian SLE patients. A cross-sectional study was conducted on 132 patients environmentally exposed to OCs. Patients were diagnosed as SLE based on the American College of Rheumatology (ACR) revised criteria. Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) score was calculated to stratify the disease severity. Blood and urine samples were collected to measure the levels of OCs, serological markers, and urinary protein. The most frequently detected OCs were p,p’-DDE; lindane; and hexachlorobenzene (HCB). The risk of developing SLE was significantly associated with detected p,p’-DDE and HCB (B value 7.704 and 14.33, respectively). Hexachlorobenzene, in addition, was significantly associated with increased SLEDAI-2K score and polycythemia. Lindane was significantly associated with hypocomplementemia, cardiac manifestations of SLE, anemia, and leucopenia. In conclusion, the detected OCs p,p’-DDE and HCB are associated with increased risk of SLE in Egyptian patients and correlates to the manifestations of disease severity.

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THE CLINICAL, LABORATORY MANIFESTATIONS AND HISTOPATHOLOGY IN NEPHROTIC PATIENTS WITH LUPUS NEPHRITIS

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2018.2.9 ◽

2018 ◽

pp. 52-58

Author(s):

Le Thuan Nguyen ◽

Bui Bao Hoang

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Nephritis ◽

Lupus Erythematosus ◽

Clinical Laboratory ◽

Activity Index ◽

Clinical Manifestations ◽

Systemic Lupus ◽

Cross Sectional ◽

Organ Systems ◽

Tubulointerstitial Lesions

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organ systems. The kidney appears to be the most commonly affected organ, especially nephrotic is a serious kidney injury. The clinical, laboratory manifestations and histopathology are very useful for diagnosis, provide the means of predicting prognosis and guiding therapy in nephrotic patients with lupus nephritis. Methods: Descriptive cross-sectional study of nephrotic patients with lupus treated in the Department of Nephrology Trung Vuong Hospital and Cho Ray Hospital between May/2014 and May/2017. Renal histopathological lesions were classified according to International Society of Nephrology/Renal Pathology Society - ISN/RPS ’s 2003. The clinical, laboratory manifestations and histopathological features were described. Results: Of 32 LN with nephritic range proteinuria cases studied, 93.7% were women. The 3 most common clinical manifestations were edema (93.8%), hypertension (96.8%) and pallor (68.9%), musculoskeletal manifestions (46.9%), malar rash (40.6%). There was significant rise in laboratory and immunological manifestions with hematuria (78.1%), Hb < 12g/dL (93.5%), increased Cholesterol (100%), and Triglycerid (87.5%), Creatinine > 1.4 mg/dL (87.5%), increased BUN 71.9%, ANA (+) 93.8%, Anti Ds DNA(+) 96.9%, low C3: 96.9%, low C4: 84.4%. The most various and severe features were noted in class IV with active tubulointerstitial lesions and high activity index. Conclusion: Lupus nephritis with nephrotic range proteinuria has the more severity of histopathological feature and the more severity of the more systemic organ involvements and laboratory disorders were noted. Key words: Systemic lupus, erythematosus (SLE) lupus nepphritis, clinical

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Cut off point of neutrophil-to-lymphocyte ratio as a marker of active disease in systemic lupus erythematosus

Lupus ◽

10.1177/0961203320950822 ◽

2020 ◽

Vol 29 (12) ◽

pp. 1566-1570

Author(s):

Akhmad Syaikhu Firizal ◽

Adhi Kristianto Sugianli ◽

Laniyati Hamijoyo

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Inflammatory Diseases ◽

Activity Index ◽

Disease Activity Index ◽

Neutrophil To Lymphocyte Ratio ◽

Systemic Lupus ◽

Cross Sectional ◽

Lymphocyte Ratio ◽

Active Disease

Aim We aimed to measure sensitivity, specificity, and to determine the cut-off value (COV) ratio of neutrophil-to-lymphocyte (NLR) in patients with active systemic lupus erythematosus (SLE). Methods A cross sectional study was conducted using the retrospective data from Hasan Sadikin Lupus Registry (HSLR). The inclusion criteria were SLE patients aged 18 years or older who had documented data of neutrophil, lymphocyte, and SLE disease activity index (SLEDAI). Patients with infections, malignancies, and other inflammatory diseases recorded in registry were excluded. SLEDAI with a score of ≤ 4 is considered inactive and score of > 4 is considered active. The neutrophil-to-lymphocyte ratio was calculated by dividing the absolute number of neutrophils by the absoulte number of lymphocytes. Receiver Operating Characteristic (ROC) curve was used to analyze and determine optimal COV of NLR. Results The total sample in this study were 112 subjects with a dominant of female (95.54%) and the mean age of 34.45 ± 9.40 years. The median of SLEDAI was 4.5 with a range from 0 to 16, while the median of NLR was 2.68 with a range of 0.59 to 19.02. The ROC analysis showed the optimal cut-off in this study was 2.94 with sensitivity and specificity as high as 60.71% and 76.79%, respectively. Conclusion Neutrophil-to-lymphocyte ratio with cut off value of 2.94 can be used to determine active disease of systemic lupus eythematousus.

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Spinal cord syndromes in patients with systemic lupus erythematosus: differentiating lupus myelitis, neuromyelitis optica, and multiple sclerosis

Lupus ◽

10.1177/0961203319886103 ◽

2019 ◽

Vol 28 (14) ◽

pp. 1656-1662

Author(s):

J N Williams ◽

C B Speyer ◽

D J Kreps ◽

D J Kimbrough ◽

K Costenbader ◽

...

Keyword(s):

Multiple Sclerosis ◽

Systemic Lupus Erythematosus ◽

Spinal Cord ◽

Disease Activity ◽

Neuromyelitis Optica ◽

Lupus Erythematosus ◽

Clinical Laboratory ◽

Activity Index ◽

Disease Activity Index ◽

Systemic Lupus

Objective Non-infectious myelitis in systemic lupus erythematosus (SLE) may be due to SLE myelitis, comorbid multiple sclerosis (MS), or neuromyelitis optica (NMO). We compared characteristics of these three conditions in SLE patients at a large academic institution. Methods We searched for neurologic diagnoses of SLE myelitis, NMO myelitis, and MS myelitis among 2297 patients with at least four 1997 American College of Rheumatology revised criteria for SLE between 2000 and 2015. Each subject was reviewed by a neurologist to confirm the underlying neurologic diagnosis. Demographic, clinical, laboratory, and radiographic data were extracted and compared using Fisher's exact test, analysis of variance, and Wilcoxon rank-sum test. Results Fifteen of the 2297 subjects with SLE (0.7%) met criteria for a spinal cord syndrome: seven had SLE myelitis, three had AQP4 seropositive NMO, and five had MS. The median SLE Disease Activity Index 2000 score at time of neurologic syndrome presentation was higher in SLE myelitis subjects (8, interquartile range (IQR) 7–16) compared with subjects with NMO (6, IQR 0–14) or MS (2, IQR 0–4), p = 0.02. Subjects with SLE myelitis were also more likely to have elevated anti-dsDNA antibodies at presentation (86%) compared with subjects with NMO (33%) or MS (0%), p = 0.03. Conclusion Myelitis occurs rarely among patients with SLE. Compared with subjects with SLE + NMO and subjects with SLE + MS, subjects with SLE myelitis had higher SLE disease activity at presentation.

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Measuring Disease Activity and Damage with Validated Metrics: A Systematic Review on Mortality and Damage in Systemic Lupus Erythematosus

The Journal of Rheumatology ◽

10.3899/jrheum.171310 ◽

2018 ◽

Vol 45 (10) ◽

pp. 1448-1461 ◽

Cited By ~ 5

Author(s):

Stephanie O. Keeling ◽

Ben Vandermeer ◽

Jorge Medina ◽

Trish Chatterley ◽

Tatiana Nevskaya ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Activity Index ◽

Damage Index ◽

Disease Activity Index ◽

Evaluation Methodology ◽

Systemic Lupus ◽

Increased Risk ◽

Damage Accrual

Objective.To identify the effect of disease activity and damage, measured by validated indices, on mortality and damage accrual, in order to inform upcoming Canadian systemic lupus erythematosus (SLE) recommendations.Methods.Following GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology to fill in evidence-to-decision tables to create recommendations for “minimal investigations needed to monitor SLE patients at baseline and subsequent visits,” a systematic literature review was performed. The effect of disease activity and damage, measured by validated metrics, on mortality and damage was systematically reviewed, with metaanalyses performed when available.Results.A title/abstract screen of 5599 articles identified 816 articles for full paper review, with 102 meeting inclusion criteria and 53 with extractable data. Thirty-three articles describing outcomes related to disease activity and 20 articles related to damage were identified. Mortality was associated with higher SLE Disease Activity Index-2000 scores in 6 studies (HR 1.14, 95% CI 1.06–1.22) and higher Systemic Lupus International Collaborating Clinics/ACR Damage Index scores in 6 studies (HR 1.53, 95% CI 1.28–1.83). Higher SLE Activity Measure scores were associated with increased risk of damage in 3 studies (OR 1.06, 95% CI 1.04–1.08). British Isles Lupus Assessment Group was associated with mortality in 1 study with HR of 1.15.Conclusion.Active SLE disease and damage are associated with and predict greater mortality and damage. The use of validated disease activity and damage metrics is important in the assessment of disease activity and damage and will inform upcoming Canadian recommendations for the assessment of SLE.

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HLA-DRB1*04 as a Risk Allele to Systemic Lupus Erythematosus and Lupus Nephritis in the Malay Population of Malaysia

Frontiers in Medicine ◽

10.3389/fmed.2020.598665 ◽

2021 ◽

Vol 7 ◽

Author(s):

Malarvili Selvaraja ◽

Voon Kin Chin ◽

Maha Abdullah ◽

Masita Arip ◽

Syafinaz Amin-Nordin

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Nephritis ◽

Lupus Erythematosus ◽

Activity Index ◽

Disease Activity Index ◽

Systemic Lupus ◽

Mortality And Morbidity ◽

Curative Therapy ◽

Multiple Organs ◽

Increased Risk

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease afflicting multiple organs. Lupus nephritis (LN) is a serious complication of SLE and remains a major cause of mortality and morbidity. Curative therapy remains unavailable as etiology from genetic and environmental factors is still unclear. The present study was conducted to elucidate the link between HLA-DRB1 gene polymorphisms with SLE and LN through clinical and laboratory/biological presentations in a population of Malaysian Malay females with SLE. A total of 100 Malay female SLE patients inclusive of 70 SLE patients without LN and 30 patients with LN were included in this study. HLA-DRB1 allele examination in SLE patients was performed using PCR-SSO, and the alleles' frequencies were compared with 951 publicly available datasets representing Malay healthy controls in Malaysia. Cytokines and free radical levels were detected by ELISA and bead-based multiplexed Luminex assays. The association between HLA-DRB1 alleles with clinical and serological manifestations and immune mediators was analyzed using different statistical approaches whenever applicable. Our study showed that HLA-DRB1*0405, HLA-DRB1*1502, and HLA-DRB1*1602 were associated with the increased risk of SLE while HLA-DRB1*1201 and HLADRB1*1202 alleles were associated with a lower risk of SLE development. Furthermore, HLA-DRB1*04 showed significant association to LN and arthritis while HLA-DRB1*15 was significantly associated with oral ulcer in Malay SLE patients. Association analysis of HLA-DRB1*04 with clinical and biological factors revealed that HLA-DRB1*04 was significantly associated with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, anti-nuclear antibody (ANA), C-reactive protein (CRP) in the blood, and total protein in the urine. SLE carriers with the HLA-DRB1*04 allele were significantly correlated to the increased levels of cytokines (IFN-y, GM-CSF, IL-17F, IL-18, IL-21, and VEGF) and were significantly showing negative correlation to IL-5 and free radicals (LPO and catalase enzyme) levels compared to SLE carriers without HLA-DRB1*04 allele. The results suggested that disease severity in SLE may be determined by HLA-DRB1 alleles. The risk of HLA-DRB1*04 allele with LN was supported by the demonstration of an intense inflammatory response in Malay SLE patients in Malaysia. More studies inclusive of a larger and multiple SLE cohorts in the future are warranted to validate these findings.

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Intestinal Microbiota and Active Systemic Lupus Erythematosus: protocol for a systematic review

10.21203/rs.3.rs-275808/v1 ◽

2021 ◽

Author(s):

Juliana Rosa Pires Vieira ◽

Andréa Toledo de Oliveira Rezende ◽

Marcos Rassi Fernandes ◽

Nilzio Antônio Silva

Keyword(s):

Systematic Review ◽

Systemic Lupus Erythematosus ◽

Intestinal Microbiota ◽

Lupus Erythematosus ◽

Activity Index ◽

Disease Activity Index ◽

Systemic Lupus ◽

Cross Sectional ◽

Assessment Development ◽

American College Of Rheumatology

Abstract BackgroundSystemic Lupus Erythematosus (SLE) is an autoimmune disease, characterized by being multi-systemic and, therefore, reaching various organs and affecting mainly young women. Its pathogenesis comprehends many factors, including the interaction between microbiota and immune system. The aim of this systematic review protocol is to assess the relationship between intestinal microbiota and SLE in activity, highlighting microbiota representative patterns regarding quantity and diversity. MethodsThe systematic review will be carried out using the following databases: Medline via PubMed, Scopus, and EMBASE. Inclusion criteria will be: observational studies (cross-sectional, cohort, and case-control) that analyzed intestinal microbiota composition in patients with SLE, with no restriction of age or sex, which fulfilled the classification criteria of either Systemic Lupus International Collaborating Clinic (SLICC), European League Against Rheumatism (EULAR) or American College of Rheumatology (ACR) and used the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) to classify disease in activity or remission. The Downs & Black Scale will be applied to analyze the risk of bias during study selection and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) will be used to assess the quality of the evidence of the selected studies.DiscussionThis review will identify investigation gaps, for better understanding of aspects related to etiopathogenesis and to the inflammatory process during SLE progression. Systematic review registration PROSPERO registration: CRD42021229322

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Photoprotection awareness and practices among patients with systemic lupus erythematosus and its association with disease activity and severity

Lupus ◽

10.1177/0961203318770016 ◽

2018 ◽

Vol 27 (8) ◽

pp. 1287-1295 ◽

Cited By ~ 4

Author(s):

W D Abdul Kadir ◽

A Jamil ◽

S Sazliyana Shaharir ◽

N Md Nor ◽

A H Abdul Gafor

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Activity Index ◽

Damage Index ◽

Disease Activity Index ◽

Sun Exposure ◽

Systemic Lupus ◽

Cross Sectional ◽

Sun Avoidance

Objective The objective of this paper is to determine photoprotection awareness, knowledge, practices, and its relationship with disease activity and damage in patients with systemic lupus erythematosus (SLE). Methods A cross-sectional study was performed. Data were acquired from in-person interviews and medical records. Results A total of 199 (89.6%) females and 23 (10.4%) males were recruited. Median age was 39.00 (interquartile range (IQR) 18) years, disease duration 12.12 (IQR 8) years, Fitzpatrick skin phototype III 119 (53.6%) and IV 81 (36.5%). Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) was 2.95 (IQR 4) while Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC-ACR DI) was 1.20 (IQR 2). The majority 205 (92.3%) were aware of sun exposure effects on SLE. Photoprotection methods were shade seeking 209 (94.1%), sun avoidance 212 (95.5%), long pants 168 (75.7%), long sleeves 155 (69.8%), sunscreen 116 (52.3%), sunglasses 114 (51.4%) and head cover 103 (46.4%). Significantly higher photoprotection practice scores (PPS) were observed in females, Malays, and individuals with higher education level and internet accessibility. PPS were not significantly correlated with SLICC-ACR DI and SLEDAI-2 K. Independent predictors for good photoprotection practice (GPP) were ethnicity (OR = 3.66, 95% CI 1.78–7.53), awareness (OR = 3.77, 95% CI 1.09–13.08) and cutaneous involvement (OR = 2.43, 95% CI 1.11–5.28). Photoprotection methods and GPP were not predictors for disease activity or damage. Conclusion Photoprotection awareness and knowledge was good. Shade seeking and sun avoidance were the common photoprotection methods practised. The use of sunscreen requires improvement. Photoprotection awareness and cutaneous manifestation were predictors for GPP. Neither photoprotection methods nor GPP were associated with disease activity or damage.

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The baseline interferon signature predicts disease severity over the subsequent 5 years in systemic lupus erythematosus

Arthritis Research & Therapy ◽

10.1186/s13075-021-02414-0 ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Lloyd Mai ◽

Arundip Asaduzzaman ◽

Babak Noamani ◽

Paul R. Fortin ◽

Dafna D. Gladman ◽

...

Keyword(s):

Gene Expression ◽

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Disease Severity ◽

Lupus Erythematosus ◽

Activity Index ◽

Type I Interferons ◽

Type I ◽

Systemic Lupus ◽

Increased Risk

Abstract Objectives Type I interferons (IFNs) play an important role in the pathophysiology of systemic lupus erythematosus (SLE). While cross-sectional data suggest an association between IFN-induced gene expression and SLE disease activity, interest in this as a biomarker of flare has been tempered by a lack of fluctuation with disease activity in the majority of patients. This led us to question whether IFN-induced gene expression might instead be a biomarker of overall disease severity, with patients with high levels spending more time in an active disease state. Methods Levels of five interferon-responsive genes were measured in the whole peripheral blood at baseline visit for 137 SLE patients subsequently followed for 5 years. Log transformed values were summed to yield a composite IFN5 score, and the correlation with various disease outcomes examined. Receiver operator characteristic analyses were performed for outcomes of interest. Kaplan-Meier curves were generated to compare the proportion of flare-free patients with high and low IFN5 scores over time. Results The baseline IFN5 score was positively correlated with the adjusted mean SLE disease activity index-2000, number of flares, adjusted mean prednisone dose, and number of new immunosuppressive medications over the subsequent 5 years. Optimal cut-offs for the IFN5 score were determined using Youden’s index and predicted more severe outcomes with 57–67% accuracy. A high baseline IFN5 level was associated with a significantly increased risk of subsequent flare. Conclusions Measurement of the type I IFN signature is a useful tool for predicting the subsequent disease activity course.

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Impact of markers of endothelial injury and hypercoagulability on systemic lupus erythematosus

Lupus ◽

10.1177/0961203319899478 ◽

2020 ◽

Vol 29 (2) ◽

pp. 182-190

Author(s):

W Batista Cicarini ◽

R C Figueiredo Duarte ◽

K Silvestre Ferreira ◽

C de Mello Gomes Loures ◽

R Vargas Consoli ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Activity Index ◽

Disease Activity Index ◽

Endothelial Injury ◽

Control Group ◽

Systemic Lupus ◽

Low Concentrations ◽

The Relationship

We have explored the relationship between possible hemostatic changes and clinical manifestation of the systemic lupus erythematosus (SLE) as a function of greater or lesser disease activity according to Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) criteria. Endothelial injury and hypercoagulability were investigated in patients with SLE by measuring thrombomodulin (TM), D-dimer (DDi) and thrombin generation (TG) potential. A total of 90 participants were distributed into three groups: 1) women with SLE presenting with low disease activity (laSLE) (SLEDAI-2K ≤ 4), 2) women with SLE presenting with moderate to high disease activity (mhaSLE) (SLEDAI-2K > 4), and 3) a control group comprising healthy women. Levels of TM and DDi were higher both in the laSLE and mhaSLE groups compared to controls and in mhaSLE compared to the laSLE group. With respect to TG assay, lagtime and endogen thrombin potential, low concentrations of tissue factor provided the best results for discrimination among groups. Analysis of these data allow us to conclude that TM, DDi and TG are potentially useful markers for discriminating patients with very active from those with lower active disease. Higher SLE activity may cause endothelial injury, resulting in higher TG and consequently a hypercoagulability state underlying the picture of thrombosis common in this inflammatory disease.

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Disease activity index is associated with subclinical atherosclerosis in childhood-onset systemic lupus erythematosus

Pediatric Rheumatology ◽

10.1186/s12969-021-00513-5 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Priscila B. S. Medeiros ◽

Roberta G. Salomão ◽

Sara R. Teixeira ◽

Diane M. Rassi ◽

Luciana Rodrigues ◽

...

Keyword(s):

Risk Factors ◽

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Activity Index ◽

Subclinical Atherosclerosis ◽

Disease Activity Index ◽

Uncontrolled Hypertension ◽

Childhood Onset ◽

Systemic Lupus

Abstract Background Systemic lupus erythematosus (SLE) is an independent risk factor for cardiovascular events. The present study determined the prevalence of subclinical atherosclerosis in childhood-onset SLE using the carotid intima-media thickness (CIMT) measurement and investigated associations between traditional and nontraditional risk factors for atherosclerosis, such as medications, SLE Disease Activity Index - SLEDAI-2 K and SLICC-ACR damage index and CIMT. Methods Cross-sectional prospective study between 2017 and 2018. CIMT was assessed by ultrasonography. Data were collected by chart review, nutritional evaluation and laboratory tests and analyzed by Fisher, Wilcoxon-Mann-Whitney tests, multiple linear and log binomial regression. Results Twenty-eight patients (mean age 13.9 years, SD 3) were enrolled. The prevalence of subclinical atherosclerosis was 32% (95% CI 14.8, 49.4). The mean CIMT was 0.43 ± 0.035 mm. The most common traditional risk factors observed were dyslipidemia (82.1%), uncontrolled hypertension (14.2%), obesity (14.3%), and poor diet (78.6%). Uncontrolled hypertension (p = 0.04), proteinuria (p = 0.02), estimated glomerular filtration rate < 75 ml /min/1.73 m2 (p = 0.02) and SLEDAI-2 K > 5 (P = 0.04) were associated with subclinical atherosclerosis. SLEDAI-2 K > 5 maintained association with CIMT after adjusting for control variables. Conclusion Subclinical atherosclerosis is frequently observed in cSLE, mainly in patients with moderate to severe disease activity.

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