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1.
Am J Clin Nutr ; 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33742198

RESUMO

BACKGROUND: Epidemiologic studies have reported a modest inverse association between dairy consumption and the risk of type 2 diabetes (T2D). Whether plasma metabolite profiles associated with dairy consumption reflect this relationship remains unknown. OBJECTIVES: We aimed to identify the plasma metabolites associated with total and specific dairy consumption, and to evaluate the association between the identified multi-metabolite profiles and T2D. METHODS: The discovery population included 1833 participants from the Prevención con Dieta Mediterránea (PREDIMED) trial. The confirmatory cohorts included 1522 PREDIMED participants at year 1 of the trial and 4932 participants from the Nurses' Health Studies (NHS), Nurses' Health Study II (NHSII), and Health Professionals Follow-Up Study US-based cohorts. Dairy consumption was assessed using validated FFQs. Plasma metabolites (n = 385) were profiled using LC-MS. We identified the dairy-related metabolite profiles using elastic net regularized regressions with a 10-fold cross-validation procedure. We evaluated the associations between the metabolite profiles and incident T2D in the discovery and the confirmatory cohorts. RESULTS: Total dairy intake was associated with 38 metabolites. C14:0 sphingomyelin (positive coefficient), C34:0 phosphatidylethanolamine (positive coefficient), and γ-butyrobetaine (negative coefficient) were associated in a directionally similar fashion with total and specific (milk, yogurt, cheese) dairy consumption. The Pearson correlation coefficients between self-reported total dairy intake and predicted total dairy intake based on the corresponding multi-metabolite profile were 0.37 (95% CI, 0.33-0.40) in the discovery cohort and 0.16 (95% CI, 0.13-0.19) in the US confirmatory cohort. After adjusting for T2D risk factors, a higher total dairy intake-related metabolite profile score was associated with a lower T2D risk [HR per 1 SD; discovery cohort: 0.76 (95% CI, 0.63-0.90); US confirmatory cohort: 0.88 (95% CI, 0.78-0.99)]. CONCLUSIONS: Total dairy intake was associated with 38 metabolites, including 3 consistently associated with dairy subtypes (C14:0 sphingomyelin, C34:0 phosphatidylethanolamine, γ-butyrobetaine). A score based on the 38 identified metabolites showed an inverse association with T2D risk in Spanish and US populations.

2.
Ann Rheum Dis ; 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33753325

RESUMO

OBJECTIVES: We sought to identify metabolic changes potentially related to rheumatoid arthritis (RA) pathogenesis occurring in the blood prior to its diagnosis. METHODS: In a US military biorepository, serum samples collected at two timepoints prior to a diagnosis of RA were identified. These were matched to controls who did not develop RA by subject age, race and time between sample collections and RA diagnosis time to stored serum samples. Relative abundances of 380 metabolites were measured using liquid chromatography-tandem mass spectrometry. We determined whether pre-RA case versus control status predicted metabolite concentration differences and differences over time (trajectories) using linear mixed models, assessing for interactions between time, pre-RA status and metabolite concentrations. We separately examined pre-RA and pre-seropositive RA cases versus matched controls and adjusted for smoking. Multiple comparison adjustment set the false discovery rate to 0.05. RESULTS: 291 pre-RA cases (80.8% pre seropositive RA) were matched to 292 controls, all with two serum samples (2.7±1.6 years; 1.0±0.9 years before RA/matched date). 52.0% were women; 52.8% were White, 26.8% Black and 20.4% other race. Mean age was 31.2 (±8.1) years at earliest blood draw. Fourteen metabolites had statistically significant trajectory differences among pre-RA subjects versus controls, including sex steroids, amino acid/lipid metabolism and xenobiotics. Results were similar when limited to pre seropositive RA and after adjusting for smoking. CONCLUSIONS: In this military case-control study, metabolite concentration trajectory differences in pre-RA cases versus controls implicated steroidogenesis, lipid/amino acid metabolism and xenobiotics in RA pathogenesis. Metabolites may have potential as biomarkers and/or therapeutic targets preceding RA diagnosis.

4.
Nat Med ; 27(3): 454-462, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33589825

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to spread relentlessly, associated with a high frequency of respiratory failure and mortality. Children experience largely asymptomatic disease, with rare reports of multisystem inflammatory syndrome in children (MIS-C). Identifying immune mechanisms that result in these disparate clinical phenotypes in children could provide critical insights into coronavirus disease 2019 (COVID-19) pathogenesis. Using systems serology, in this study we observed in 25 children with acute mild COVID-19 a functional phagocyte and complement-activating IgG response to SARS-CoV-2, similar to the acute responses generated in adults with mild disease. Conversely, IgA and neutrophil responses were significantly expanded in adults with severe disease. Moreover, weeks after the resolution of SARS-CoV-2 infection, children who develop MIS-C maintained highly inflammatory monocyte-activating SARS-CoV-2 IgG antibodies, distinguishable from acute disease in children but with antibody levels similar to those in convalescent adults. Collectively, these data provide unique insights into the potential mechanisms of IgG and IgA that might underlie differential disease severity as well as unexpected complications in children infected with SARS-CoV-2.


Assuntos
Anticorpos Antivirais/sangue , /imunologia , Adolescente , Adulto , Idade de Início , Idoso , Anticorpos Neutralizantes/análise , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/análise , Infecções Assintomáticas , /patologia , Portador Sadio/sangue , Portador Sadio/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Imunidade/fisiologia , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Pandemias , Índice de Gravidade de Doença , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/epidemiologia , Adulto Jovem
6.
Med (N Y) ; 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33283203

RESUMO

Background: Small studies have correlated hypertension with pneumonia risk; whether this is recapitulated in larger prospective studies, and represents a causal association, is unclear. Methods: We estimated the risk for prevalent hypertension with incident respiratory diseases over mean follow-up of 8 years among 377,143 British participants in the UK Biobank. Mendelian randomization of blood pressure on pneumonia was implemented using 75 independent, genome-wide significant variants associated with systolic and diastolic blood pressures among 299,024 individuals not in the UK Biobank. Secondary analyses with pulmonary function tests were performed. Findings: In total, 107,310 participants (30%) had hypertension at UK Biobank enrollment, and 9,969 (3%) developed pneumonia during follow-up. Prevalent hypertension was independently associated with increased risk for incident pneumonia (HR: 1.36; 95% CI: 1.29-1.43; p < 0.001), as well as other incident respiratory diseases. Genetic predisposition to a 5 mm Hg increase in blood pressure was associated with increased risk for incident pneumonia for systolic blood pressure (HR: 1.08; 95% CI: 1.04-1.13; p < 0.001) and diastolic blood pressure (HR: 1.11; 95% CI: 1.03-1.20; p = 0.005). Additionally, consistent with epidemiologic associations, increased blood pressure genetic risk was significantly associated with reduced performance on pulmonary function tests (p < 0.001). Conclusions: These results suggest that elevated blood pressure increases risk for pneumonia. Maintaining adequate blood pressure control, in addition to other measures, may reduce risk for pneumonia. Funding: S.M.Z. (1F30HL149180-01), M.H. (T32HL094301-07), and P.N. (R01HL1427, R01HL148565, and R01HL148050) are supported by the National Institutes of Health. J.P. is supported by the John S. LaDue Memorial Fellowship.

7.
medRxiv ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33236019

RESUMO

Age is the dominant risk factor for infectious diseases, but the mechanisms linking the two are incompletely understood 1,2 . Age-related mosaic chromosomal alterations (mCAs) detected from blood-derived DNA genotyping, are structural somatic variants associated with aberrant leukocyte cell counts, hematological malignancy, and mortality 3-11 . Whether mCAs represent independent risk factors for infection is unknown. Here we use genome-wide genotyping of blood DNA to show that mCAs predispose to diverse infectious diseases. We analyzed mCAs from 767,891 individuals without hematological cancer at DNA acquisition across four countries. Expanded mCA (cell fraction >10%) prevalence approached 4% by 60 years of age and was associated with diverse incident infections, including sepsis, pneumonia, and coronavirus disease 2019 (COVID-19) hospitalization. A genome-wide association study of expanded mCAs identified 63 significant loci. Germline genetic alleles associated with expanded mCAs were enriched at transcriptional regulatory sites for immune cells. Our results link mCAs with impaired immunity and predisposition to infections. Furthermore, these findings may also have important implications for the ongoing COVID-19 pandemic, particularly in prioritizing individual preventive strategies and evaluating immunization responses.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33052715

RESUMO

RATIONALE: Glucagon-like peptide-1 receptor (GLP-1R) agonists are approved to treat type 2 diabetes mellitus and obesity. GLP-1R agonists reduce airway inflammation and hyperresponsiveness in preclinical models. OBJECTIVES: To compare rates of asthma exacerbations and symptoms between type 2 diabetic adults with asthma prescribed GLP-1R agonists and those prescribed sodium-glucose cotransporter-2 (SGLT-2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, sulfonylureas or basal insulin for diabetes treatment intensification. METHODS: Electronic health records-based new-user, active comparator, retrospective cohort study of patients with type 2 diabetes and asthma newly prescribed GLP-1R agonists or comparator drugs, January 2000-March 2018. Primary outcome was asthma exacerbations; secondary outcome was encounters for asthma symptoms. Propensity scores were calculated for GLP-1R agonist and non-GLP-1R agonist use. Zero-inflated Poisson regression models included adjustment for multiple covariates. MEASUREMENTS AND MAIN RESULTS: Patients initiating GLP-1R agonists (n=448), SGLT-2 inhibitors (n=112), DPP-4 inhibitors (n=435), sulfonylureas (n=2,253) or basal insulin (n=2,692), were identified. At six months, asthma exacerbation counts were lower in persons initiating GLP-1R agonists (reference) compared to SGLT-2 inhibitors (incidence rate ratio [IRR], 2.98 [95% CI, 1.30 to 6.80]), DPP-4 inhibitors (IRR, 2.45 [95% CI, 1.54 to 3.89]), sulfonylureas (IRR, 1.83 [95% CI, 1.20 to 2.77]) and basal insulin (IRR, 2.58 [95% CI, 1.72 to 3.88]). Encounters for asthma symptoms were also lower among GLP-1R agonist users. CONCLUSIONS: Adult asthmatics prescribed GLP-1R agonists for type 2 diabetes had lower counts of asthma exacerbations compared to other drugs initiated for treatment intensification. GLP-1R agonists may represent a novel treatment for asthma associated with metabolic dysfunction.

9.
Lupus ; : 961203320966378, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33092467

RESUMO

OBJECTIVES: Early detection of autoimmune rheumatic diseases is crucial given their high morbidity and mortality and short window of opportunity to improve patient outcomes. Self-administered screening questionnaires such as the connective tissue disease screening questionnaire (CSQ) have been shown to promote early detection of autoimmune rheumatic diseases. However, optimal scoring of screening questionnaires may differ with prevalence of clinical features and changes in classification criteria. We compared the performance of 3 scoring methods for the CSQ for early detection of autoimmune rheumatic diseases in a multi-ethnic Asian population. METHODS: Patients who were newly referred for evaluation of possible autoimmune rheumatic diseases were invited to answer the cross-culturally adapted CSQ. Detection of autoimmune rheumatic diseases using 1) the original CSQ scoring, 2) a modified CSQ scoring and 3) a scoring based on current classification criteria, were compared to classification of autoimmune rheumatic diseases by classification criteria. RESULTS: Of 819 participants, 85 were classified as having autoimmune rheumatic diseases screened for by the adapted CSQ. The original CSQ scoring yielded relatively lower sensitivities in detecting both any and individual autoimmune rheumatic diseases (67% and 20-57%, respectively) compared to the modified CSQ scoring (81% and 60-73%, respectively) and the scoring based on current classification criteria (89% and 50-88%, respectively). CONCLUSION: The adapted CSQ with the classification criteria-based scoring achieved relatively high sensitivities in detecting autoimmune rheumatic diseases, suggesting this could be employed as the first step in population screening.

10.
Sleep ; 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32954408

RESUMO

STUDY OBJECTIVES: Implementation of electronic health record biobanks has facilitated linkage between clinical and questionnaire data and enabled assessments of relationships between sleep health and diseases in phenome-wide association studies (PheWAS). In the Mass General Brigham Biobank, a large health system-based study, we aimed to systematically catalog associations between time in bed, sleep timing and weekly variability with diseases derived from ICD-9/10 codes. METHODS: Self-reported habitual bed and wake times were used to derive variables: short (<7hr) and long (≥9hr) time in bed, sleep midpoint, social jetlag, and sleep debt. Logistic regression and Cox proportional hazards models were used to test cross-sectional and prospective associations, respectively, adjusted for age, gender, race/ethnicity, and employment status, and further adjusted for BMI. RESULTS: In cross-sectional analysis (n=34,651), sleep variable associations were most notable for circulatory system, mental disorders, and endocrine/metabolic diseases. We observed the strongest associations for short time in bed with obesity, for long time in bed and sleep midpoint with Major depressive disorder, for social jetlag with Hypercholesterolemia, and for sleep debt with Acne. In prospective analysis (n=24,065), we observed short time in bed associations with higher incidence of Acute pain, and later sleep midpoint and higher sleep debt and social jetlag associations with higher incidence of Major depressive disorder. CONCLUSION: Our analysis reinforced that sleep health is a multidimensional construct, corroborated robust known findings from traditional cohort studies, and supported the application of PheWAS as a promising tool for advancing sleep research. Considering the exploratory nature of PheWAS, careful interrogation of novel findings is imperative.

11.
medRxiv ; 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32909004

RESUMO

The human beta coronavirus SARS-CoV-2, causative virus of COVID-19, has infected more than 15 million people globally and continues to spread. Widespread, population level testing to detect active and past infections is critical to curb the COVID-19 pandemic. Antibody (serological) testing is the only option for detecting past infections outside the narrow window accessible to nucleic acid-based tests. However, currently available serological assays commonly lack scalability. Here, we describe the development of a rapid homogenous serological assay for the detection of antibodies to SARS-CoV-2 in patient plasma. We show that the fluorescence-based assay accurately detects seroconversion in COVID-19 patients from less than 1 microliter of plasma. Using a cohort of samples from COVID-19 infected or healthy individuals, we demonstrate detection with 100% sensitivity and specificity. This assay addresses an important need for a robust, low barrier to implementation, and scalable serological assay with complementary strengths to currently available serological platforms.

12.
Arthritis Rheumatol ; 72(11): 1863-1871, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32969204

RESUMO

OBJECTIVE: To identify interactions between genetic factors and current or recent smoking in relation to risk of developing systemic lupus erythematosus (SLE). METHODS: For the study, 673 patients with SLE (diagnosed according to the American College of Rheumatology 1997 updated classification criteria) were matched by age, sex, and race (first 3 genetic principal components) to 3,272 control subjects without a history of connective tissue disease. Smoking status was classified as current smoking/having recently quit smoking within 4 years before diagnosis (or matched index date for controls) versus distant past/never smoking. In total, 86 single-nucleotide polymorphisms and 10 classic HLA alleles previously associated with SLE were included in a weighted genetic risk score (wGRS), with scores dichotomized as either low or high based on the median value in control subjects (low wGRS being defined as less than or equal to the control median; high wGRS being defined as greater than the control median). Conditional logistic regression models were used to estimate both the risk of SLE and risk of anti-double-stranded DNA autoantibody-positive (dsDNA+) SLE. Additive interactions were assessed using the attributable proportion (AP) due to interaction, and multiplicative interactions were assessed using a chi-square test (with 1 degree of freedom) for the wGRS and for individual risk alleles. Separate repeated analyses were carried out among subjects of European ancestry only. RESULTS: The mean ± SD age of the SLE patients at the time of diagnosis was 36.4 ± 15.3 years. Among the 673 SLE patients included, 92.3% were female and 59.3% were dsDNA+. Ethnic distributions were as follows: 75.6% of European ancestry, 4.5% of Asian ancestry, 11.7% of African ancestry, and 8.2% classified as other ancestry. A high wGRS (odds ratio [OR] 2.0, P = 1.0 × 10-51 versus low wGRS) and a status of current/recent smoking (OR 1.5, P = 0.0003 versus distant past/never smoking) were strongly associated with SLE risk, with significant additive interaction (AP 0.33, P = 0.0012), and associations with the risk of anti-dsDNA+ SLE were even stronger. No significant multiplicative interactions with the total wGRS (P = 0.58) or with the HLA-only wGRS (P = 0.06) were found. Findings were similar in analyses restricted to only subjects of European ancestry. CONCLUSION: The strong additive interaction between an updated SLE genetic risk score and current/recent smoking suggests that smoking may influence specific genes in the pathogenesis of SLE.

13.
Am J Clin Nutr ; 112(6): 1613-1630, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-32936887

RESUMO

BACKGROUND: Adherence to a healthy diet has been associated with reduced risk of chronic diseases. Identifying nutritional biomarkers of diet quality may be complementary to traditional questionnaire-based methods and may provide insights concerning disease mechanisms and prevention. OBJECTIVE: To identify metabolites associated with diet quality assessed via the Alternate Healthy Eating Index (AHEI) and its components. METHODS: This cross-sectional study used FFQ data and plasma metabolomic profiles, mostly lipid related, from the Nurses' Health Study (NHS, n = 1460) and Health Professionals Follow-up Study (HPFS, n = 1051). Linear regression models assessed associations of the AHEI and its components with individual metabolites. Canonical correspondence analyses (CCAs) investigated overlapping patterns between AHEI components and metabolites. Principal component analysis (PCA) and explanatory factor analysis were used to consolidate correlated metabolites into uncorrelated factors. We used stepwise multivariable regression to create a metabolomic score that is an indicator of diet quality. RESULTS: The AHEI was associated with 83 metabolites in the NHS and 96 metabolites in the HPFS after false discovery rate adjustment. Sixty-three of these significant metabolites overlapped between the 2 cohorts. CCA identified "healthy" AHEI components (e.g., nuts, whole grains) and metabolites (n = 27 in the NHS and 33 in the HPFS) and "unhealthy" AHEI components (e.g., red meat, trans fat) and metabolites (n = 56 in the NHS and 63 in the HPFS). PCA-derived factors composed of highly saturated triglycerides, plasmalogens, and acylcarnitines were associated with unhealthy AHEI components while factors composed of highly unsaturated triglycerides were linked to healthy AHEI components. The stepwise regression analysis contributed to a metabolomics score as a predictor of diet quality. CONCLUSION: We identified metabolites associated with healthy and unhealthy eating behaviors. The observed associations were largely similar between men and women, suggesting that metabolomics can be a complementary approach to self-reported diet in studies of diet and chronic disease.

14.
Artigo em Inglês | MEDLINE | ID: mdl-32936999

RESUMO

OBJECTIVE: Knowledge remains scarce regarding diet and SLE risk. We investigated four dietary quality scores and SLE risk overall and by anti-dsDNA positive (+) versus negative (-) subtypes. METHODS: We studied 79,568 women in the Nurses' Health Study (NHS, 1984-2014) and 93,554 in the NHSII (1991-2013). Using validated food frequency questionnaires, we calculated four dietary scores: the 2010 Alternative Healthy Eating Index [AHEI-2010], Alternative Mediterranean Diet Score (1), Dietary Approach to Stop Hypertension [DASH], and Empirical Dietary Inflammatory Pattern [EDIP]. Incident SLE was confirmed by medical record review. Time-varying Cox regression models estimated pooled hazard ratios (HRs [95% confidence intervals]) of SLE risk, overall and by anti-dsDNA, for cumulative average dietary quality score tertiles and individual AHEI-2010 components. RESULTS: We identified 194 incident SLE cases. SLE risk was similar in women with the highest (vs. lowest) dietary scores (AHEI-2010: HR 0.78 [95% CI 0.54-1.14], aMed: HR 0.82 [95% CI 0.56-1.18], DASH: HR 1.16 [95% CI 0.81-1.66], EDIP: HR 0.83 [95% CI 0.57-1.21]). No association was demonstrated for dsDNA+ or dsDNA- SLE risk. Women in the highest (vs. lowest) AHEI-2010 tertile of nut/legume intake had a decreased SLE risk (HR 0.59 [95% CI 0.40-0.87]). No association was demonstrated for other AHEI-2010 components and SLE risk. CONCLUSION: We observed no association between long-term adherence to the AHEI-2010, aMed, DASH, or EDIP scores with SLE risk, suggesting a large effect of dietary quality on SLE risk is unlikely. However, potential reduction in overall SLE risk with high nut/legume intake warrants further investigation.

16.
Artigo em Inglês | MEDLINE | ID: mdl-32619290

RESUMO

BACKGROUND: Smoking has been associated with increased systemic lupus erythematosus (SLE) risk, but the biologic basis for this association is unknown. We investigated whether women's smoking was positively associated with SLE-associated pro-inflammatory chemokines/cytokines, [stem cell factor (SCF), B-lymphocyte stimulator (BLyS), interferon-inducible protein-10 (IP-10), interferon-alpha (IFN-α)]; or negatively associated with anti-inflammatory cytokine interleukin-10 (IL-10)]; and whether associations were modified by SLE-related autoantibody status. METHODS: The Nurses' Health Study (NHS, n=121,700) and NHSII (n=116,429) cohorts were begun in 1976 and 1989. In 1988-1990 (NHS) and 1996-1999 (NHSII), ~25% participants donated blood samples. We identified 1177 women without SLE with banked samples and tested by ELISA for chemokines/cytokines as well as anti-Sm, -Ro/SSA, La/SSB and RNP. Antinuclear antibodies (ANA) were detected by HEp-2 cell indirect immunofluorescence and anti-double-stranded DNA antibodies and were assayed by ELISA. Smoking was assessed until blood draw. Separate tobit and linear regression analyses, adjusted for potential confounders, modeled associations between smoking and log-transformed chemokine/cytokine concentrations. Analyses were stratified by autoantibody status. Effect estimates were calculated as ratios of geometric means, expressed as % differences. RESULTS: Among the 15% current/recent vs. 85% past/never smokers, BLyS levels were 8.7% higher (p<0.01), and were 24% higher (p<0.0001) among those ANA+. Current/recent smokers had IL-10 concentrations 46% lower (p<0.01) than past/never smokers; each 10 pack-years of smoking was associated with -17% IL-10 (p <0.001). Smoking was not associated with IP-10 or SCF. CONCLUSIONS: Elevated BLyS and lower IL-10 levels among current smokers, particularly among ANA+ women, may be involved in SLE pathogenesis.

17.
medRxiv ; 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32607518

RESUMO

Background Seroepidemiology is an important tool to characterize the epidemiology and immunobiology of SARS-CoV-2 but many immunoassays have not been externally validated raising questions about reliability of study findings. To ensure meaningful data, particularly in a low seroprevalence population, assays need to be rigorously characterized with high specificity. Methods We evaluated two commercial (Roche Diagnostics and Epitope Diagnostics IgM/IgG) and two non-commercial (Simoa and Ragon/MGH IgG) immunoassays against 68 confirmed positive and 232 pre-pandemic negative controls. Sensitivity was stratified by time from symptom onset. The Simoa multiplex assay applied three pre-defined algorithm models to determine sample result. Results The Roche and Ragon/MGH IgG assays each registered 1/232 false positive, the primary Simoa model registered 2/232 false positives, and the Epitope registered 2/230 and 3/230 false positives for the IgG and IgM assays respectively. Sensitivity >21 days post symptom-onset was 100% for all assays except Epitope IgM, but lower and/or with greater variability between assays for samples collected 9-14 days (67-100%) and 15-21 days (69-100%) post-symptom onset. The Simoa and Epitope IgG assays demonstrated excellent sensitivity earlier in the disease course. The Roche and Ragon/MGH IgG assays were less sensitive during early disease, particularly among immunosuppressed individuals. Conclusions The Epitope IgG demonstrated good sensitivity and specificity. The Roche and Ragon/MGH IgG assays registered rare false positives with lower early sensitivity. The Simoa assay primary model had excellent sensitivity and few false positives.

18.
J Rheumatol ; 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32669445

RESUMO

OBJECTIVE: Being overweight or obese increases rheumatoid arthritis (RA) risk among women, particularly among those diagnosed at a younger age. Abdominal obesity may contribute to systemic inflammation more than general obesity; thus, we investigated whether abdominal obesity, compared to general obesity, predicted RA risk in 2 prospective cohorts: the Nurses' Health Study (NHS) and NHS II. METHODS: We followed 50,682 women (1986-2014) in NHS and 47,597 women (1993-2015) in NHS II, without RA at baseline. Waist circumference (WC), BMI, health outcomes, and covariate data were collected through biennial questionnaires. Incident RA cases and serologic status were identified by chart review. We examined the associations of WC and BMI with RA risk using time-varying Cox proportional hazards models. We repeated analyses restricted to age ≤ 55 years. RESULTS: During 28 years of follow-up, we identified 844 incident RA cases (527 NHS, 317 NHS II). Women with WC > 88 cm (35 in) had increased RA risk (HR 1.22, 95% CI 1.06-1.41). A similar association was observed for seropositive RA, which was stronger among young and middle-aged women. Further adjustment for BMI attenuated the association to null. In contrast, BMI was associated with RA (HRBMI ≥ 30 vs < 25 1.33, 95% CI 1.05-1.68) and seropositive RA, even after adjusting for WC, and, as in WC analyses, this association was stronger among young and middle-aged women. CONCLUSION: Abdominal obesity was associated with increased RA risk, particularly for seropositive RA, among young and middle-aged women; however, it did not independently contribute to RA risk beyond general obesity.

19.
Lupus ; 29(8): 976-982, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32507075

RESUMO

OBJECTIVES: Moderate alcohol consumption has been associated with decreased systemic lupus erythematosus risk, but the biologic basis for this association is unknown. We aimed to determine whether moderate alcohol consumption was associated with lower concentrations of systemic lupus erythematosus-associated chemokines/cytokines in an ongoing cohort of female nurses without systemic lupus erythematosus, and whether the association was modified by the presence of systemic lupus erythematosus-related autoantibodies. METHODS: About 25% of participants from the Nurses' Health Study (n = 121,700 women) and Nurses' Health Study 2 (n = 116,429) donated a blood sample; of these, 1177 women were without systemic lupus erythematosus at time of donation. Cumulative average and current (within 4 years) intakes of beer, wine or liquor were assessed from pre-blood draw questionnaires. Chemokine/cytokine concentrations (stem cell factor, B-lymphocyte stimulator, interferon-inducible protein-10, interferon-alpha, interleukin-10) and antibodies against dsDNA and extractable nuclear antigens were obtained using enzyme-linked immunosorbent assays. Antinuclear antibodies were detected by indirect immunofluorescence on HEp-2 cells. RESULTS: At blood draw, the women's mean age was 56 years and 22% were antinuclear antibody positive; 36% were African-American. About half (46%) reported consuming 0-5 g/day of alcohol. Stem cell factor levels were 0.5% lower (p < 0.0001) for every gram per day increase in cumulative average alcohol consumption. Women who consumed >5 g/day had mean stem cell factor levels 7% lower (p = 0.002) than non-drinkers. Other cytokines were not significantly associated with alcohol intake. Autoantibody status did not modify observed associations. CONCLUSION: In this study of female nurses, moderate alcohol consumption was associated with lower stem cell factor levels, suggesting a plausible mechanism through which alcohol may lower systemic lupus erythematosus risk might be by decreasing circulating stem cell factor.

20.
J Am Coll Cardiol ; 75(22): 2769-2780, 2020 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-32498804

RESUMO

BACKGROUND: Polygenic risk scores (PRS) for coronary artery disease (CAD) identify high-risk individuals more likely to benefit from primary prevention statin therapy. Whether polygenic CAD risk is captured by conventional paradigms for assessing clinical cardiovascular risk remains unclear. OBJECTIVES: This study sought to intersect polygenic risk with guideline-based recommendations and management patterns for CAD primary prevention. METHODS: A genome-wide CAD PRS was applied to 47,108 individuals across 3 U.S. health care systems. The authors then assessed whether primary prevention patients at high polygenic risk might be distinguished on the basis of greater guideline-recommended statin eligibility and higher rates of statin therapy. RESULTS: Of 47,108 study participants, the mean age was 60 years, and 11,020 (23.4%) had CAD. The CAD PRS strongly associated with prevalent CAD (odds ratio: 1.4 per SD increase in PRS; p < 0.0001). High polygenic risk (top 20% of PRS) conferred 1.9-fold odds of developing CAD (p < 0.0001). However, among primary prevention patients (n = 33,251), high polygenic risk did not correspond with increased recommendations for statin therapy per the American College of Cardiology/American Heart Association (46.2% for those with high PRS vs. 46.8% for all others, p = 0.54) or U.S. Preventive Services Task Force (43.7% vs. 43.7%, p = 0.99) or higher rates of statin prescriptions (25.0% vs. 23.8%, p = 0.04). An additional 4.1% of primary prevention patients may be recommended for statin therapy if high CAD PRS were considered a guideline-based risk-enhancing factor. CONCLUSIONS: Current paradigms for primary cardiovascular prevention incompletely capture a polygenic susceptibility to CAD. An opportunity may exist to improve CAD prevention efforts by integrating both genetic and clinical risk.

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