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1.
Int J Rheum Dis ; 2019 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-31762221

RESUMO

AIM: Systemic lupus erythematosus (SLE) causes irreversible damage to organ systems. Recently, evidence has been obtained for subphenotypes of SLE. This study aimed to identify damage clusters and compare the associated clinical manifestations, SLE disease activity, mortality, and genetic risk scores (GRS). METHODS: The study was conducted on the Hanyang BAE lupus cohort. Patients with disease duration <5 years were excluded to minimize confounding effects of disease duration. They were grouped into 3 clusters based on the Systemic Lupus International Collaborating Clinics Damage Index using k-means cluster analysis. RESULTS: Among the 1130 analyzed patients, musculoskeletal damage was most prevalent (20.2%), followed by ocular (11.4%), renal (10.5%), and neuropsychiatric damage (10.2%). Three significantly different damage clusters were identified. Patients in cluster 1 (n = 824) showed the least damage. Cluster 2 (n = 195) was characterized by frequent renal (55.4%) and ocular (58.0%) damage, and cluster 3 (n = 111) was dominated by neuropsychiatric (100%) and musculoskeletal damage (35.1%). Cluster 2 had the highest adjusted mean AMS (adjusted mean SLE Disease Activity Index score; mean ± SD: 5.4 ± 2.9), while cluster 3 had the highest mortality (14.4%). Weighted GRS did not differ significantly between the clusters. CONCLUSION: Patients in prevalent renal and ocular damage cluster had the highest AMS scores, while the cluster with frequent neuropsychiatric damage had the highest mortality.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31609532

RESUMO

OBJECTIVES: There is a paucity of data regarding healthcare costs associated with damage accrual in systemic lupus erythematosus (SLE). We describe costs associated with damage states across the disease course using multi-state modeling. METHODS: Patients from 33 centres in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. Annual data on demographics, disease activity, damage (SLICC/American College of Rheumatology (ACR) Damage Index [SDI]), hospitalizations, medications, dialysis, and selected procedures were collected. Ten-year cumulative costs (Canadian dollars) were estimated by multiplying annual costs associated with each SDI state by the expected state duration using a multi-state model. RESULTS: 1687 patients participated, 88.7% female, 49.0% of Caucasian race/ethnicity, mean age at diagnosis 34.6 years (SD 13.3), and mean follow up 8.9 years (range 0.6-18.5). Annual costs were higher in those with higher SDIs (SDI ≥ 5: $22 006 2019 CDN, 95% CI $16 662, $27 350 versus SDI=0: $1833, 95% CI $1134, $2532). Similarly, 10-year cumulative costs were higher in those with higher SDIs at the beginning of the 10-year interval (SDI ≥ 5: $189 073, 95% CI $142 318, $235 827 versus SDI=0: $21 713, 95% CI $13 639, $29 788). CONCLUSION: Patients with the highest SDIs incur 10-year cumulative costs that are almost 9-fold higher than those with the lowest SDIs. By estimating the damage trajectory and incorporating annual costs, damage can be used to estimate future costs, critical knowledge for evaluating the cost-effectiveness of novel therapies.

3.
J Autoimmun ; : 102340, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31629628

RESUMO

OBJECTIVE: The soluble urokinase plasminogen activator receptor (suPAR) has potential as a prognosis and severity biomarker in several inflammatory and infectious diseases. In a previous cross-sectional study, suPAR levels were shown to reflect damage accrual in cases of systemic lupus erythematosus (SLE). Herein, we evaluated suPAR as a predictor of future organ damage in recent-onset SLE. METHODS: Included were 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who met the 1997 American College of Rheumatology classification criteria with 5-years of follow-up data available. Baseline sera from patients and age- and sex-matched controls were assayed for suPAR. Organ damage was assessed annually using the SLICC/ACR damage index (SDI). RESULTS: The levels of suPAR were higher in patients who accrued damage, particularly those with SDI≥2 at 5 years (N = 32, 46.8% increase, p = 0.004), as compared to patients without damage. Logistic regression analysis revealed a significant impact of suPAR on SDI outcome (SDI≥2; OR = 1.14; 95% CI 1.03-1.26), also after adjustment for confounding factors. In an optimized logistic regression to predict damage, suPAR persisted as a predictor, together with baseline disease activity (SLEDAI-2K), age, and non-Caucasian ethnicity (model AUC = 0.77). Dissecting SDI into organ systems revealed higher suPAR levels in patients who developed musculoskeletal damage (SDI≥1; p = 0.007). CONCLUSION: Prognostic biomarkers identify patients who are at risk of acquiring early damage and therefore need careful observation and targeted treatment strategies. Overall, suPAR constitutes an interesting biomarker for patient stratification and for identifying SLE patients who are at risk of acquiring organ damage during the first 5 years of disease.

4.
Arthritis Rheumatol ; 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31631584

RESUMO

OBJECTIVE: The Systemic Lupus International Collaborating Clinics (SLICC) frailty index (FI) has been shown to predict mortality, but its association with other important outcomes is unknown. We examined the association of baseline SLICC-FI values with damage accrual in the SLICC inception cohort. METHODS: The baseline visit was defined as the first at which both organ damage (SLICC/ACR Damage Index [SDI]) and health-related quality of life (Short-Form 36 [SF-36]) were assessed. Baseline SLICC-FI scores were calculated. Damage accrual was measured by the increase in SDI between the baseline assessment and the last study visit. Multivariable negative binomial regression estimated the association between baseline SLICC-FI values and the rate of increase in the SDI during follow-up, adjusting for relevant demographic and clinical characteristics. RESULTS: The 1549 SLE patients eligible for this analysis were mostly female (88.7%) with mean (standard deviation, SD) age 35.7 (13.3) years and median (interquartile range) disease duration 1.2 (0.9-1.5) years at baseline. Mean (SD) baseline SLICC-FI was 0.17 (0.08) with a range of 0-0.51. Over a mean (SD) follow-up of 7.2 (3.7) years, 653 patients (42.2%) had an increase in SDI. Higher baseline SLICC-FI values (per 0.05 increment) were associated with higher rates of increase in the SDI during follow-up (Incidence Rate Ratio [IRR] 1.19; 95% CI 1.13-1.25), after adjusting for age, sex, ethnicity/region, education, baseline SLEDAI-2K, baseline SDI, and baseline use of corticosteroids, antimalarials, and immunosuppressives. CONCLUSION: The SLICC-FI predicts damage accrual in incident SLE, which further supports the SLICC-FI as a valid health measure in SLE.

6.
Arthritis Rheumatol ; 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31390162

RESUMO

OBJECTIVE: To determine the frequency, clinical characteristics, associations, and outcomes of different types of peripheral nervous system (PNS) disease in a multiethnic/multiracial, prospective inception cohort of systemic lupus erythematosus (SLE) patients. METHODS: Patients were evaluated annually for 19 neuropsychiatric (NP) events including 7 types of PNS disease. SLE disease activity, organ damage, autoantibodies, and patient and physician assessment of outcome were measured. Time to event and linear regressions were used as appropriate. RESULTS: Of 1,827 SLE patients, 88.8% were female, and 48.8% were white. The mean ± SD age was 35.1 ± 13.3 years, disease duration at enrollment was 5.6 ± 4.2 months, and follow-up was 7.6 ± 4.6 years. There were 161 PNS events in 139 (7.6%) of 1,827 patients. The predominant events were peripheral neuropathy (66 of 161 [41.0%]), mononeuropathy (44 of 161 [27.3%]), and cranial neuropathy (39 of 161 [24.2%]), and the majority were attributed to SLE. Multivariate Cox regressions suggested longer time to resolution in patients with a history of neuropathy, older age at SLE diagnosis, higher SLE Disease Activity Index 2000 scores, and for peripheral neuropathy versus other neuropathies. Neuropathy was associated with significantly lower Short Form 36 (SF-36) physical and mental component summary scores versus no NP events. According to physician assessment, the majority of neuropathies resolved or improved over time, which was associated with improvements in SF-36 summary scores for peripheral neuropathy and mononeuropathy. CONCLUSION: PNS disease is an important component of total NPSLE and has a significant negative impact on health-related quality of life. The outcome is favorable for most patients, but our findings indicate that several factors are associated with longer time to resolution.

7.
Arthritis Res Ther ; 21(1): 195, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462329

RESUMO

BACKGROUND: Structural variations such as copy number variations (CNVs) have a functional impact on various human traits. This study profiled genome-wide CNVs in Korean patients with rheumatoid arthritis (RA) to investigate the efficacy of treatment with TNF-α blockers. METHODS: A total of 357 Korean patients with RA were examined for the efficacy of TNF-α blocker treatment. Disease activity indexes were measured at baseline and 6 months after the treatment. The patients were classified as responders and non-responders based on the change in disease activity indexes according to the EULAR response criteria. CNVs in the same patients were profiled using fluorescence signal intensity data generated by a genome-wide SNP array. The association of CNVs with response to TNF-α blockers was analyzed by multivariate logistic regression accounting for genetic background and clinical factors including body mass index, gender, baseline disease activity, TNF-α blocker used, and methotrexate treatment. RESULTS: The study subjects varied in their responses to TNF-α blockers and had 286 common CNVs in autosomes. We identified that the 3.8-kb deletion at 2q14.3 in 5% of the subjects was associated with response to TNF-α blockers (1.37 × 10- 5 ≤ P ≤ 4.07 × 10- 4) at a false discovery rate threshold of 5%. The deletion in the identified CNV was significantly more frequent in the non-responders than in the responders, indicating worse response to TNF-α blockers in the deletion carriers. The 3.8-kb deletion at 2q14.3 is located in an intergenic region with the binding sites of two transcription factors, MAFF and MAFK. CONCLUSIONS: This study obtained the CNV landscape of Korean patients with RA and identified the common regional deletion associated with poor response to treatment with TNF-α blockers.

8.
Postgrad Med J ; 95(1125): 378-381, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31127051

RESUMO

OBJECTIVE: To search out whether or not years of education is causally related to rheumatoid arthritis (RA). METHOD: We conducted a two-sample Mendelian randomisation (MR) analysis employing inverse-variance weighted (IVW), weighted median and MR-Egger regression analysis. We chose statistic data of years of education from the UK Biobank genome-wide association studies (GWASs) (n=293 723) as the exposure and a meta-analysis of GWASs of RA with autoantibody (n=5539) and European controls (n=20 169) as the outcome. RESULTS: We selected a total of 49 single nucleotide polymorphisms as instrumental variables (IVs). The IVW method instructed an inverse causative relationship between years of education and RA (ß=- 0.039, SE=0.283, p=0.008). MR-Egger regression test showed that directional pleiotropy seems not to bias the MR results (intercept=0.028; p=0.358). MR-Egger analysis demonstrated no causative relationship between RA and years of education (ß=- 2.320, SE=1.709, p=0.181). However, the weighted median approach indicated a causative association between RA and years of education (ß=-0.950, SE=0.355, p=0.008). CONCLUSIONS: The MR analysis supported a potential inverse causative relationship between years of education and development of RA.

9.
Int J Rheum Dis ; 22(7): 1239-1246, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31090187

RESUMO

AIM: To estimate incidence rate (IR) and risk factors for opportunistic infections (OI) in early rheumatoid arthritis (RA) patients. METHODS: Retrospective cohorts were identified in the Korean National Claims Database. Incident RA cases were recruited in 2010 (n = 14 081). Follow up was ended at the time of development of new OI or at the date of last visit within 12 months of diagnosis. The IR and standardized incidence ratio (SIR) of OI in early and overall RA (n = 226 838) over a year were calculated. A multivariable regression model was used to identify risk factors for OI in early RA. RESULTS: The IR of OI in early and overall RA were 3.81/100 and 3.67/100 person-years, respectively. The SIR for OI in early RA was 1.14 (95% CI, 1.05-1.23). Herpes zoster (SIR = 1.12, 95% CI, 1.03-1.22) and candidiasis (SIR = 2.40, 95% CI, 1.55-3.54) were common in early RA. Age (50 < age ≤ 60 [OR 1.74, 95% CI, 1.30-2.33], 60 < age ≤ 70 [OR 1.85, 95% CI, 1.36-2.52], age > 70 [OR 1.89, 95% CI, 1.34-2.68]), female sex (OR 1.40, 95% CI, 1.12-1.74), comorbidities (one comorbidity [OR 1.53, 95% CI, 1.24-1.89], ≥ two comorbidities [OR 1.84, 95% CI, 1.47-2.29]), and corticosteroid use of 5 mg/d or more (OR 1.38, 95% CI, 1.13-1.69) were significantly associated with increased risk of OI in early RA. CONCLUSION: Opportunistic infections, especially for herpes zoster and candidiasis, tend to occur more often in early RA than in overall RA. Age, female sex, comorbidities and corticosteroid use are related to increased OI in early RA patients.

10.
J Rheumatol ; 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30988130

RESUMO

OBJECTIVE: To construct a Frailty Index (FI) as a measure of vulnerability to adverse outcomes among patients with systemic lupus erythematosus (SLE), using data from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort. METHODS: The SLICC inception cohort consists of recently diagnosed patients with SLE followed annually with clinical and laboratory assessments. For this analysis, the baseline visit was defined as the first study visit at which sufficient information was available for construction of an FI. Following a standard procedure, variables from the SLICC database were evaluated as potential health deficits. Selected health deficits were then used to generate a SLICC-FI. The prevalence of frailty in the baseline dataset was evaluated using established cutpoints for FI values. RESULTS: The 1683 patients with SLE (92.1% of the overall cohort) eligible for inclusion in the baseline dataset were mostly female (89%) with mean (SD) age 35.7 (13.4) years and mean (SD) disease duration 18.8 (15.7) months at baseline. Of 222 variables, 48 met criteria for inclusion in the SLICC-FI. Mean (SD) SLICC-FI was 0.17 (0.08) with a range from 0 to 0.51. At baseline, 27.1% (95% CI 25.0-29.2) of patients were classified as frail, based on SLICC-FI values > 0.21. CONCLUSION: The SLICC inception cohort permits feasible construction of an FI for use in patients with SLE. Even in a relatively young cohort of patients with SLE, frailty was common. The SLICC-FI may be a useful tool for identifying patients with SLE who are most vulnerable to adverse outcomes, but validation of this index is required prior to its use.

11.
PLoS Genet ; 15(4): e1008092, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31022184

RESUMO

Human leukocyte antigen (HLA) is a key genetic factor conferring risk of systemic lupus erythematosus (SLE), but precise independent localization of HLA effects is extremely challenging. As a result, the contribution of specific HLA alleles and amino-acid residues to the overall risk of SLE and to risk of specific autoantibodies are far from completely understood. Here, we dissected (a) overall SLE association signals across HLA, (b) HLA-peptide interaction, and (c) residue-autoantibody association. Classical alleles, SNPs, and amino-acid residues of eight HLA genes were imputed across 4,915 SLE cases and 13,513 controls from Eastern Asia. We performed association followed by conditional analysis across HLA, assessing both overall SLE risk and risk of autoantibody production. DR15 alleles HLA-DRB1*15:01 (P = 1.4x10-27, odds ratio (OR) = 1.57) and HLA-DQB1*06:02 (P = 7.4x10-23, OR = 1.55) formed the most significant haplotype (OR = 2.33). Conditioned protein-residue signals were stronger than allele signals and mapped predominantly to HLA-DRB1 residue 13 (P = 2.2x10-75) and its proxy position 11 (P = 1.1x10-67), followed by HLA-DRB1-37 (P = 4.5x10-24). After conditioning on HLA-DRB1, novel associations at HLA-A-70 (P = 1.4x10-8), HLA-DPB1-35 (P = 9.0x10-16), HLA-DQB1-37 (P = 2.7x10-14), and HLA-B-9 (P = 6.5x10-15) emerged. Together, these seven residues increased the proportion of explained heritability due to HLA to 2.6%. Risk residues for both overall disease and hallmark autoantibodies (i.e., nRNP: DRB1-11, P = 2.0x10-14; DRB1-13, P = 2.9x10-13; DRB1-30, P = 3.9x10-14) localized to the peptide-binding groove of HLA-DRB1. Enrichment for specific amino-acid characteristics in the peptide-binding groove correlated with overall SLE risk and with autoantibody presence. Risk residues were in primarily negatively charged side-chains, in contrast with rheumatoid arthritis. We identified novel SLE signals in HLA Class I loci (HLA-A, HLA-B), and localized primary Class II signals to five residues in HLA-DRB1, HLA-DPB1, and HLA-DQB1. These findings provide insights about the mechanisms by which the risk residues interact with each other to produce autoantibodies and are involved in SLE pathophysiology.


Assuntos
Sequência de Aminoácidos , Autoanticorpos/imunologia , Suscetibilidade a Doenças , Antígenos de Histocompatibilidade Classe II/química , Antígenos de Histocompatibilidade Classe II/imunologia , Antígenos de Histocompatibilidade Classe I/química , Antígenos de Histocompatibilidade Classe I/imunologia , Lúpus Eritematoso Sistêmico/etiologia , Alelos , Substituição de Aminoácidos , Grupo com Ancestrais do Continente Asiático , Feminino , Predisposição Genética para Doença , Variação Genética , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe II/genética , Humanos , Masculino , Razão de Chances , Polimorfismo de Nucleotídeo Único
12.
PLoS One ; 14(4): e0214981, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31002669

RESUMO

OBJECTIVE: Remission is a key goal in managing rheumatoid arthritis (RA), with sustained remission as the preferred sequelae of short-term remission. However little is known about the predictors of sustained remission for patients reaching remission. Using two independent cohorts, we aimed to evaluate the prevalence and predictors for sustained remission. METHODS: The study cohort consisted of subjects with RA from the Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS) and the Korean Observational Study Network for Arthritis (KORONA). We analyzed subjects who reached remission in 2009 with follow up data for two consecutive years. Remission was defined by the Disease Activity Score 28- (DAS28-CRP) of less than 2.6. Sustained remission was defined as three consecutive annual visits in remission. Predictors for sustained remission were identified by multivariate logistic regression analysis. RESULTS: A total of 465 subjects were in remission in 2009. Sustained remission was achieved by 53 of 92 (57.5%) in BRASS and by 198 of 373 (53.1%) in KORONA. In multivariate analyses, baseline predictors of sustained remission were: disease duration less than 5 years [odds ratio (OR) 1.96, 95% confidence interval (95% CI) 1.08-3.58], Modified Health Assessment Questionnaire (MHAQ) score of 0 (OR 1.80, 95% CI 1.18-2.74), and non-use of oral glucocorticoid (OR 1.58, 95% CI 1.01-2.47). CONCLUSION: More than half of RA subjects in remission in 2009 remained in remission through 2011. Short disease duration, no disability, and non-use of oral glucocorticoid at baseline were associated with sustained remission.

13.
Anal Chem ; 91(7): 4868-4875, 2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30848879

RESUMO

The viscosity of biofluids can be used to acquire meaningful medical information on the conditions of a patient but has seldom been utilized in clinical practices owing to cumbersome measurement procedures and the need for large sample volumes. We present a colorimetric method to measure the viscosity of blood plasma using a paper-based viscometer developed in this study specifically for clinical diagnosis. The proposed analytical device consists of multilayered papers with fluid-loading, -mixing, and -measuring regions, and it can be fabricated readily in a simple manner using three-layered paper channels and tape. Moreover, the colorimetric analysis enables viscosity estimations by analyzing a single optical image. To validate the device performance, we measured the viscosities of fluids such as glycerin aqueous solutions, bovine-serum-albumin solution, dimethyl sulfoxide, and blood plasma. We found that the measured viscosities were in good agreement with the reference values. Finally, we developed a simple smartphone application for the viscosity measurements that helped enhance the convenience and utility of the paper-based viscometer while maintaining the measurement accuracy.

14.
Clin Rheumatol ; 38(8): 2141-2149, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30868319

RESUMO

OBJECTIVES: We reviewed the associations between paraoxonase 1 (PON1) polymorphisms and susceptibility and PON1 activity in rheumatoid arthritis (RA) patients and compared PON1 activity between RA patients and controls. METHODS: We conducted a meta-analysis of PON1 Q192R and L55M polymorphism and RA risk data and determined the associations between PON1 Q192R polymorphism and PON1 activity in RA patients. We also compared serum/plasma PON1 activity levels in RA patients and controls. RESULTS: Twelve studies were included in this meta-analysis. No association was observed between RA and the PON1 192R allele in any study subject (OR = 0.967, 95% CI = 0.829-1.129, p = 0.674). Analysis using recessive, dominant, or homozygous contrast models revealed no association between the PON1 192R allele and RA. Meta-analysis showed no association between RA and the PON1 55M allele (OR = 1.400, 95% CI = 0.738-2.658, p = 0.308). In the meta-analysis, PON1 activity was significantly higher in the RR genotype than in the QQ (SMD = 2.975, 95% CI = 2.157-3.792, p < 0.001) and QR (SMD = 1.265, 95% CI = 0.898-1.633, p < 0.001) genotypes. PON1 activity was significantly lower in the RA group than in the control group (SMD = - 3.176, 95% CI = - 5.070 to - 1.283, p < 0.001). CONCLUSIONS: We found no association between the PON1 Q192R and L55M polymorphisms and susceptibility to RA, while PON1 Q192R polymorphism was associated with PON1 activity in RA patients; we found significantly lower PON1 activity in RA patients.Key points• PON1 Q192R polymorphism is associated with PON1 activity in RA patients..• PON1 activity is significantly lower in RA patients..

15.
Eur J Clin Invest ; 49(4): e13076, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30710354

RESUMO

OBJECTIVE: This study aimed to examine whether body mass index (BMI) is causally associated with rheumatoid arthritis (RA). METHOD: A two-sample Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW), weighted median and MR-Egger regression methods was performed. We used the publicly available summary statistics data sets of genome-wide association studies (GWAS) meta-analyses for BMI in individuals of European descent (n = 322 154; GIANT consortium) as the exposure and a GWAS for noncancer illness code self-reported: RA from the individuals included in the UK Biobank (total n = 337 159; case = 7480, control = 329 679) as the outcome. RESULTS: We selected 68 single nucleotide polymorphisms at genome-wide significance from GWASs on BMI as the instrumental variables. The IVW method showed evidence to support a causal association between BMI and RA (beta = 0.003, SE = 0.001, P = 0.033). MR-Egger regression revealed that directional pleiotropy was unlikely to be biasing the result (intercept = -3.54E-05; P = 0.736), but it showed no causal association between BMI and RA (beta = 0.004, SE = 0.004, P = 0.302). However, the weighted median approach yielded evidence of a causal association between BMI and RA (beta = 0.006, SE = 0.002, P = 0.004). Cochran's Q test and the funnel plot indicated no evidence of heterogeneity and asymmetry, indicating no directional pleiotropy. CONCLUSION: The results of MR analysis support that BMI may be causally associated with an increased risk of RA.

16.
Sci Rep ; 9(1): 1337, 2019 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-30718717

RESUMO

Strong genetic associations in the region containing human leukocyte antigen (HLA) genes have been well-documented in various human immune disorders. Imputation methods to infer HLA variants from single nucleotide polymorphism (SNP) genotypes are currently used to understand HLA associations with a trait of interest. However, it is challenging for some researchers to obtain individual-level SNP genotype data or reference haplotype data. In this study, we developed and evaluated a new method, DISH (direct imputing summary association statistics of HLA variants), for imputing summary association statistics of HLA variants from SNP summary association statistics based on linkage disequilibria in Asian and European populations. Disease association Z scores in DISH were highly correlated with those from imputed HLA genotypes in null model datasets (r = 0.934 in Asians; r = 0.960 in Europeans). We applied DISH to two previous GWAS datasets in Asian systemic lupus erythematosus and European rheumatoid arthritis populations. There was a high correlation between Z scores in the DISH and HLA genotype imputations, showing the same disease-susceptible and protective alleles. This study illustrated the usefulness of the DISH method in understanding and identifying disease-associated HLA variants in human diseases while maintaining individual-level data security.

17.
Rheumatology (Oxford) ; 58(7): 1259-1267, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30753683

RESUMO

OBJECTIVES: To assess the prevalence of combined hormonal contraceptives (CHCs) in reproductive-age women with SLE with and without possible contraindications and to determine factors associated with their use in the presence of possible contraindications. METHODS: This observational cohort study included premenopausal women ages 18-45 years enrolled in the SLICC Registry ⩽15 months after SLE onset, with annual assessments spanning 2000-2017. World Health Organization Category 3 or 4 contraindications to CHCs (e.g. hypertension, aPL) were assessed at each study visit. High disease activity (SLEDAI score >12 or use of >0.5 mg/kg/day of prednisone) was considered a relative contraindication. RESULTS: A total of 927 SLE women contributed 6315 visits, of which 3811 (60%) occurred in the presence of one or more possible contraindication to CHCs. Women used CHCs during 512 (8%) visits, of which 281 (55%) took place in the setting of one or more possible contraindication. The most frequently observed contraindications were aPL (52%), hypertension (34%) and migraine with aura (22%). Women with one or more contraindication were slightly less likely to be taking CHCs [7% of visits (95% CI 7, 8)] than women with no contraindications [9% (95% CI 8, 10)]. CONCLUSION: CHC use was low compared with general population estimates (>35%) and more than half of CHC users had at least one possible contraindication. Many yet unmeasured factors, including patient preferences, may have contributed to these observations. Further work should also aim to clarify outcomes associated with this exposure.

18.
Arthritis Rheumatol ; 71(8): 1297-1307, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30771242

RESUMO

OBJECTIVE: To evaluate the properties of a frailty index (FI), constructed using data from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort, as a novel health measure in systemic lupus erythematosus (SLE). METHODS: For this secondary analysis, the baseline visit was defined as the first study visit at which both organ damage (SLICC/American College of Rheumatology Damage Index [SDI]) and health-related quality of life (Short-Form 36 [SF-36] scores) were assessed. The SLICC-FI was constructed using baseline data. The SLICC-FI comprises 48 health deficits, including items related to organ damage, disease activity, comorbidities, and functional status. Content, construct, and criterion validity of the SLICC-FI were assessed. Multivariable Cox regression was used to estimate the association between baseline SLICC-FI values and mortality risk, adjusting for demographic and clinical factors. RESULTS: In the baseline data set of 1,683 patients with SLE, 89% were female, the mean ± SD age was 35.7 ± 13.4 years, and the mean ± SD disease duration was 18.8 ± 15.7 months. At baseline, the mean ± SD SLICC-FI score was 0.17 ± 0.08 (range 0-0.51). Baseline SLICC-FI values exhibited the expected measurement properties and were weakly correlated with baseline SDI scores (r = 0.26, P < 0.0001). Higher baseline SLICC-FI values (per 0.05 increment) were associated with increased mortality risk (hazard ratio 1.59, 95% confidence interval 1.35-1.87), after adjusting for age, sex, steroid use, ethnicity/region, and baseline SDI scores. CONCLUSION: The SLICC-FI demonstrates internal validity as a health measure in SLE and might be used to predict future mortality risk. The SLICC-FI is potentially valuable for quantifying vulnerability among patients with SLE, and adds to existing prognostic scores.

19.
Int J Rheum Dis ; 22(5): 852-859, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30677239

RESUMO

AIM: Despite high clinical disease activity, some patients with active rheumatoid arthritis (RA) have normal acute phase reactant (APR) values. This study aimed to determine the clinical outcomes of active RA patients with normal APR values. METHOD: Of 5376 patients with RA enrolled in the Korean observational study network for arthritis (KORONA) registry, 400 patients with disease duration of <2 years who had Clinical Disease Activity Index (CDAI) score of >2.8 at baseline, biologic-naïve, and erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) drawn at both baseline and 2-year follow-up visits were identified. Patients were grouped according to baseline APR levels: normal APRs, one APR elevated, and both APRs elevated. RESULTS: Baseline tender and swollen joint counts, mean CDAI and Health Assessment Questionnaire-Disability Index (HAQ-DI) scores were significantly lower in the normal APRs group compared with APR-elevated groups (P < 0.0001). At 2-year follow-up, mean CDAI scores, HAQ-DI, and percentage of the patient achieving remission were not significantly different between the normal APRs group compared with the APR-elevated groups regardless of the baseline disease activity. However, in patients with baseline CDAI moderate to high disease activity, the normal APRs group less frequently required initiation of the biologic disease-modifying anti-rheumatic drugs compared with the APR-elevated groups (P = 0.044). CONCLUSION: Active RA patients with normal APR values have milder disease presentation, but similar clinical outcomes to those with elevated APRs.

20.
J Rheumatol ; 46(5): 492-500, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30647177

RESUMO

OBJECTIVE: In cross-sectional studies, elevated osteopontin (OPN) levels have been proposed to reflect, and/or precede, progressive organ damage and disease severity in systemic lupus erythematosus (SLE). We aimed, in a cohort of patients with recent-onset SLE, to determine whether raised serum OPN levels precede damage and/or are associated with disease activity or certain disease phenotypes. METHODS: We included 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who had 5 years of followup data available. All patients fulfilled the 1997 American College of Rheumatology (ACR) criteria. Baseline sera from patients and from age- and sex-matched population-based controls were analyzed for OPN using ELISA. Disease activity and damage were assessed at each annual followup visit using the SLE Disease Activity Index 2000 (SLEDAI-2K) and the SLICC/ACR damage index (SDI), respectively. RESULTS: Compared to controls, baseline OPN was raised 4-fold in SLE cases (p < 0.0001). After relevant adjustments in a binary logistic regression model, OPN levels failed to significantly predict global damage accrual defined as SDI ≥ 1 at 5 years. However, baseline OPN correlated with SLEDAI-2K at enrollment into the cohort (r = 0.27, p < 0.0001), and patients with high disease activity (SLEDAI-2K ≥ 5) had raised serum OPN (p < 0.0001). In addition, higher OPN levels were found in patients with persistent disease activity (p = 0.0006), in cases with renal involvement (p < 0.0001) and impaired estimated glomerular filtration rate (p = 0.01). CONCLUSION: The performance of OPN to predict development of organ damage was not impressive. However, OPN associated significantly with lupus nephritis and with raised disease activity at enrollment, as well as over time.

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