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  • 1
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    Online Resource
    Factors Associated with Arterial Vascular Events in PROFILE: A Multiethnic Lupus Cohort
    SAGE Publications ; 2009
    In:  Lupus Vol. 18, No. 11 ( 2009-10), p. 958-965
    Details
    In: Lupus, SAGE Publications, Vol. 18, No. 11 ( 2009-10), p. 958-965
    Abstract: The objective of this study was to determine the factors associated with the occurrence of arterial vascular events in a multiethnic systemic lupus erythematosus (SLE) cohort. The PROFILE cohort, comprised SLE patients ( n = 1333) of defined ethnicity from five different US institutions, was studied to determine demographic, clinical and biological variables associated with vascular events. An arterial vascular event (first episode) was either a myocardial infarction, angina pectoris and/or a vascular procedure for myocardial infarction, stroke, claudication and/or evidence of gangrene. Patient characteristics were analyzed by univariable and multivariable Cox proportional hazards regression analyses. One-hundred twenty-three (9.8%) patients had at least one incident arterial event. Age at cohort enrollment (HR = 1.04, 95% CI 1.03–1.06), smoking (HR = 2.20, 95% CI 1.40–3.46) and the CRP2* C alleles (HR = 1.91, 95% CI 1.04–3.49) were associated with a shorter time-to-the occurrence of arterial vascular events. Some clinical manifestations of disease activity were associated with a shorter time-to-occurrence [psychosis (HR = 2.21, 95% CI 1.10–4.44), seizures (HR = 1.85, 95% CI 1.00–3.24) and anaemia (HR = 1.83, 95% CI 1.02–3.31)], but others were not [arthritis (HR = 0.32, 95% CI 0.18–0.58)] . In conclusion, older patients, especially in the context of a predisposing environmental factor (smoking) and severe clinical manifestations, are at higher risk of having arterial vascular events. The genetic contribution of the variation at the CRP locus was not obscured by demographic or clinical variables. Awareness of these factors should lead to more effective management strategies of patients at risk for arterial vascular events.
    Type of Medium: Online Resource
    ISSN: 0961-2033 , 1477-0962
    URL: Article
    DOI: 10.1177/0961203309104862
    RVK:
    XA 10000
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2009
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  • 2
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    Analysis of the influence of PTPN22 gene polymorphisms in systemic sclerosis
    BMJ ; 2011
    In:  Annals of the Rheumatic Diseases Vol. 70, No. 3 ( 2011-03), p. 454-462
    Details
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 70, No. 3 ( 2011-03), p. 454-462
    Abstract: Two functional single nucleotide polymorphisms (SNP) in the PTPN22 gene (rs24746601 and rs33996649) have been associated with autoimmunity. The aim of this study was to investigate the role of the R263Q SNP for the first time and to re-evaluate the role of the R620W SNP in the genetic predisposition to systemic sclerosis (SSc) susceptibility and clinical phenotypes. Methods 3422 SSc patients (2020 with limited cutaneous SSc and 1208 with diffuse cutaneous SSc) and 3638 healthy controls of Caucasian ancestry from an initial case--control set of Spain and seven additional independent replication cohorts were included in our study. Both rs33996649 and rs2476601 PTPN22 polymorphisms were genotyped by TaqMan allelic discrimination assay. A meta-analysis was performed to test the overall effect of these PTPN22 polymorphisms in SSc. Results The meta-analysis revealed evidence of association of the rs2476601 T allele with SSc susceptibility (p FDRcorrected =0.03 pooled, OR 1.15, 95% CI 1.03 to 1.28). In addition, the rs2476601 T allele was significantly associated with anticentromere-positive status (p FDRcorrected =0.02 pooled, OR 1.22, 95% CI 1.05 to 1.42). Although the rs33996649 A allele was significantly associated with SSc in the Spanish population (p FDRcorrected =0.04, OR 0.58, 95% CI 0.36 to 0.92), this association was not confirmed in the meta-analysis (p=0.36 pooled, OR 0.89, 95% CI 0.72 to 1.1). Conclusion The study suggests that the PTPN22 R620W polymorphism influences SSc genetic susceptibility but the novel R263Q genetic variant does not. These data strengthen evidence that the R620W mutation is a common risk factor in autoimmune diseases.
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    URL: Article
    DOI: 10.1136/ard.2010.130138
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2011
    detail.hit.zdb_id: 1481557-6
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  • 3
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    Adolescent onset of lupus results in more aggressive disease and worse outcomes: results of a nested matched case–control study within LUMINA, a multiethnic US cohort (LUMINA LVII)
    SAGE Publications ; 2008
    In:  Lupus Vol. 17, No. 4 ( 2008-04), p. 314-322
    Details
    In: Lupus, SAGE Publications, Vol. 17, No. 4 ( 2008-04), p. 314-322
    Abstract: The objective of this study is to examine the clinical features and outcomes of patients with systemic lupus erythematosus (SLE) whose disease began in adolescence [juvenile-onset SLE (jSLE)] compared with adult-onset patients [adult-onset SLE (aSLE)] from a large multiethnic cohort. Systemic lupus erythematosus patients of African-American, Caucasian, or Hispanic ethnicity and ≥1 year follow-up were studied in two groups: jSLE (diagnosed at ≤18 years); aSLE (diagnosed at 19–50 years; matched for gender and disease duration at enrolment). Sociodemographic data, SLE manifestations, disease activity, damage accrual, SLE-related hospitalizations or emergency room visits, drug utilization, mortality and psychosocial characteristics and quality of life were compared. Data were analysed by univariable and multivariable analyses. Seventy-nine patients were studied (31 jSLE, 48 aSLE); 90% were women. Mean (SD) total disease duration was 6.8 (2.7) years in jSLE and 5.6 (3.3) years in aSLE ( p = 0.077). Mean age at cohort entry was 18.4 (1.8) and 33.9 (9.2) years in jSLE and aSLE respectively. By univariable analysis, jSLE patients were more commonly of African-American descent, were more likely to have renal and neurological involvements, and to accrue renal damage; jSLE patients had lower levels of helplessness and scored higher in the physical component measure of the SF-36 than aSLE patients. Renal involvement [OR = 1.549, 95% CI (1.397–15.856)] and neurological involvem ent [OR = 1.642, 95% CI (1.689–15.786)] were independently associated with jSLE by multivariable analysis. There was a larger proportion of African-Americans within the jSLE group. After adjusting for ethnicity and follow-up time, jSLE patients experienced more renal and neurological manifestations, with more renal damage. There was a two-fold higher mortality rate in the jSLE group.
    Type of Medium: Online Resource
    ISSN: 0961-2033 , 1477-0962
    URL: Article
    DOI: 10.1177/0961203307087875
    RVK:
    XA 10000
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2008
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  • 4
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    Effect of hydroxychloroquine treatment on pro-inflammatory cytokines and disease activity in SLE patients: data from LUMINA (LXXV), a multiethnic US cohort
    SAGE Publications ; 2012
    In:  Lupus Vol. 21, No. 8 ( 2012-07), p. 830-835
    Details
    In: Lupus, SAGE Publications, Vol. 21, No. 8 ( 2012-07), p. 830-835
    Abstract: Objective: We sought to determine the effect of hydroxychloroquine therapy on the levels proinflammatory/prothrombotic markers and disease activity scores in patients with systemic lupus erythematosus (SLE) in a multiethnic, multi-center cohort (LUMINA). Methods: Plasma/serum samples from SLE patients ( n = 35) were evaluated at baseline and after hydroxychloroquine treatment. Disease activity was assessed using SLAM-R scores. Interferon (IFN)-α2, interleukin (IL)-1β, IL-6, IL-8, inducible protein (IP)-10, monocyte chemotactic protein-1, tumor necrosis factor (TNF)-α and soluble CD40 ligand (sCD40L) levels were determined by a multiplex immunoassay. Anticardiolipin antibodies were evaluated using ELISA assays. Thirty-two frequency-matched plasma/serum samples from healthy donors were used as controls. Results: Levels of IL-6, IP-10, sCD40L, IFN-α and TNF-α were significantly elevated in SLE patients versus controls. There was a positive but moderate correlation between SLAM-R scores at baseline and levels of IFN-α ( p = 0.0546). Hydroxychloroquine therapy resulted in a significant decrease in SLAM-R scores ( p = 0.0157), and the decrease in SLAM-R after hydroxychloroquine therapy strongly correlated with decreases in IFN-α ( p = 0.0087). Conclusions: Hydroxychloroquine therapy resulted in significant clinical improvement in SLE patients, which strongly correlated with reductions in IFN-α levels. This indicates an important role for the inhibition of endogenous TLR activation in the action of hydroxychloroquine in SLE and provides additional evidence for the importance of type I interferons in the pathogenesis of SLE. This study underscores the use of hydroxychloroquine in the treatment of SLE.
    Type of Medium: Online Resource
    ISSN: 0961-2033 , 1477-0962
    URL: Article
    DOI: 10.1177/0961203312437270
    RVK:
    XA 10000
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2012
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  • 5
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    Predictors of the rate of change in disease activity over time in LUMINA, a multiethnic US cohort of patients with systemic lupus erythematosus: LUMINA LXX
    SAGE Publications ; 2010
    In:  Lupus Vol. 19, No. 6 ( 2010-05), p. 727-733
    Details
    In: Lupus, SAGE Publications, Vol. 19, No. 6 ( 2010-05), p. 727-733
    Abstract: The objectives of the present study were (1) to clarify and quantify the relationship between age and disease duration with the rate of change in disease activity over time in patients with systemic lupus erythematosus (SLE) and (2) to explore other possible factors associated with this rate of change. To this end, SLE patients from LUMINA were studied if they had at least three visits in which disease activity (Systemic Lupus Activity Measure—Revised [SLAM-R]) had been ascertained. Variables associated with the rate (slope) of change in disease activity (obtained by regressing the SLAM-R score against the length of time from diagnosis to visit date) were examined by univariable and multivariable analyses. Five hundred and forty two of the 632 patients had at least three SLAM-R score. In multivariable analyses, Whites exhibited the fastest decline in disease activity, Texan Hispanics exhibited the slowest, trailed by the African Americans. Longer disease duration and HLA-DRB1*1503 positivity were associated with a slower decline whereas a greater number of American College of Rheumatology criteria and abnormal laboratory parameters (white blood cell counts, hematocrit and serum creatinine) were associated with a faster decline. These findings complement existing knowledge on SLE disease activity and are potentially useful to clinicians managing these patients. Lupus (2010) 19, 727—733.
    Type of Medium: Online Resource
    ISSN: 0961-2033 , 1477-0962
    URL: Article
    DOI: 10.1177/0961203309359289
    RVK:
    XA 10000
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2010
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  • 6
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    Peripheral vascular damage in systemic lupus erythematosus: data from LUMINA, a large multi-ethnic U.S. cohort (LXIX)
    SAGE Publications ; 2009
    In:  Lupus Vol. 18, No. 14 ( 2009-12), p. 1303-1308
    Details
    In: Lupus, SAGE Publications, Vol. 18, No. 14 ( 2009-12), p. 1303-1308
    Abstract: To determine the factors associated with peripheral vascular damage in systemic lupus erythematosus patients and its impact on survival from Lupus in Minorities, Nature versus Nurture, a longitudinal US multi-ethnic cohort. Peripheral vascular damage was defined by the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Factors associated with peripheral vascular damage were examined by univariable and multi-variable logistic regression models and its impact on survival by a Cox multi-variable regression. Thirty-four (5.3%) of 637 patients (90% women, mean [SD] age 36.5 [12.6] [16—87] years) developed peripheral vascular damage. Age and the SDI (without peripheral vascular damage) were statistically significant (odds ratio [OR] = 1.05, 95% confidence interval [CI] 1.01—1.08; P = 0.0107 and OR = 1.30, 95% CI 0.09—1.56; P = 0.0043, respectively) in multi-variable analyses. Azathioprine, warfarin and statins were also statistically significant, and glucocorticoid use was borderline statistically significant (OR = 1.03, 95% CI 0.10—1.06; P = 0.0975). In the survival analysis, peripheral vascular damage was independently associated with a diminished survival (hazard ratio = 2.36; 95% CI 1.07—5.19; P = 0.0334). In short, age was independently associated with peripheral vascular damage, but so was the presence of damage in other organs (ocular, neuropsychiatric, renal, cardiovascular, pulmonary, musculoskeletal and integument) and some medications (probably reflecting more severe disease). Peripheral vascular damage also negatively affected survival. Lupus (2009) 18, 1303—1308.
    Type of Medium: Online Resource
    ISSN: 0961-2033 , 1477-0962
    URL: Article
    DOI: 10.1177/0961203309105877
    RVK:
    XA 10000
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2009
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  • 7
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    Online Resource
    Effect of age, menopause and cyclophosphamide use on damage accrual in systemic lupus erythematosus patients from LUMINA, a multiethnic US cohort (LUMINA LXIII)
    SAGE Publications ; 2009
    In:  Lupus Vol. 18, No. 2 ( 2009-02), p. 184-186
    Details
    In: Lupus, SAGE Publications, Vol. 18, No. 2 ( 2009-02), p. 184-186
    Type of Medium: Online Resource
    ISSN: 0961-2033 , 1477-0962
    URL: Article
    DOI: 10.1177/0961203308098988
    RVK:
    XA 10000
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2009
    detail.hit.zdb_id: 2008035-9
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  • 8
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    Online Resource
    Time to seizure occurrence and damage in PROFILE, a multi-ethnic systemic lupus erythematosus cohort
    SAGE Publications ; 2008
    In:  Lupus Vol. 17, No. 3 ( 2008-03), p. 177-184
    Details
    In: Lupus, SAGE Publications, Vol. 17, No. 3 ( 2008-03), p. 177-184
    Abstract: Abstract The objective of this study was to determine risk factors predicting seizures and damage caused by seizures in a multi-ethnic systemic lupus erythematosus cohort (PROFILE) that includes systemic lupus erythematosus patients ( n = 1295) from five different US institutions. Only patients with seizures after systemic lupus erythematosus diagnosis (incident) were included in the analyses of clinical seizures (80/1295, 6.2%), but all patients (prevalent and incident) were included in the analyses of damage caused by seizures (51/1295, 3.9%). We examined socioeconomic–demographic, clinical, and genetic variables predictive of clinical seizures and damage from seizures by Cox proportional hazard ratios (HR) and 95% confidence intervals (CI). Independent predictors of a shorter time to the occurrence of clinical seizures were younger age (HR = 1.0; 95% CI 0.9–1.0), having Hispanic-Texan ethnicity (HR = 2.7; 95% CI 1.3–5.7) or African-American ethnicity (HR = 1.8; 95% CI 1.0–3.1), and the previous occurrence of a cerebrovascular accident (HR = 3.3; 95% CI 1.6–7.1) or an episode of psychosis (HR = 2.4; 95% CI 1.1–5.0), whereas the previous occurrence of photosensitivity (HR = 0.5; 95% CI 0.3–0.9) was the only independent predictor of a longer time to the occurrence of clinical seizures. Independent predictors of a shorter time to the occurrence of damage caused by seizures were younger age (HR = 1.0; 95% CI 0.9–1.0), male gender (HR = 2.4; 95% CI 1.1–5.4), and the occurrence of a previous cerebrovascular accident (HR = 2.7; 95% CI 1.0–7.0) or an episode of psychosis (HR = 4.7; 95% CI 2.3–9.9). No allele from the candidate genes examined ( HLA-DRB1, HLA-DQB1, FCGR2A, FCGR3A, or FCG3B) predicted clinical seizures or damage caused by seizures.
    Type of Medium: Online Resource
    ISSN: 0961-2033 , 1477-0962
    URL: Article
    DOI: 10.1177/0961203307086639
    RVK:
    XA 10000
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2008
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  • 9
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    Online Resource
    Measuring therapeutic adherence in systemic lupus erythematosus with electronic monitoring
    SAGE Publications ; 2012
    In:  Lupus Vol. 21, No. 11 ( 2012-10), p. 1158-1165
    Details
    In: Lupus, SAGE Publications, Vol. 21, No. 11 ( 2012-10), p. 1158-1165
    Abstract: Objective: We used an electronic monitoring system to quantify adherence to prescribed oral therapies by patients with systemic lupus erythematosus (SLE). Methods: Participants were included from a larger longitudinal study cohort of 110 patients recruited from publicly-funded rheumatology clinics, 78 of whom agreed to have their SLE drug therapy electronically monitored for two years with the Medication Events Monitoring System (MEMS®, AARDEX Group). Adherence was determined as the percentage of days (weeks for methotrexate) the patient took the medication as prescribed by the physician. Collected data included SLEDAI; SLICC damage index for SLE (SDI); medical outcome study social support survey (MOS-SSS); Center for Epidemiologic Studies depression scale (CESD); and quality of life (SF-12). Results: Ninety percent of the cohort was female, 45% were Hispanic, and 49% were African-American. Mean age was 36.3 years, disease duration was 5.9 years, SLEDAI score was 3.2, and SDI score was 0.9. Adherence was 62% for all drugs combined and did not differ significantly for individual medications. Patients with more depression ( p  〈  0.02), and higher number of pills taken daily ( p  〈  0.02) were more likely to be non-adherent. Only one-fourth of the patients had an average adherence of ≥80%; these patients had a better mental component score (SF-12) at 24 months than non-adherent patients ( p  〈  0.01). Conclusions: Electronic monitoring demonstrated that only one-fourth of the patients had an adherence rate ≥80%. Polypharmacy and depression were associated with non-adherence.
    Type of Medium: Online Resource
    ISSN: 0961-2033 , 1477-0962
    URL: Article
    DOI: 10.1177/0961203312447868
    RVK:
    XA 10000
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2012
    detail.hit.zdb_id: 2008035-9
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  • 10
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    Online Resource
    Lack of association of a functionally relevant single nucleotide polymorphism of matrix metalloproteinase-1 promoter with systemic sclerosis (scleroderma)
    Springer Science and Business Media LLC ; 2001
    In:  Genes & Immunity Vol. 2, No. 5 ( 2001-08-01), p. 273-275
    Details
    In: Genes & Immunity, Springer Science and Business Media LLC, Vol. 2, No. 5 ( 2001-08-01), p. 273-275
    Type of Medium: Online Resource
    ISSN: 1466-4879 , 1476-5470
    URL: Article
    DOI: 10.1038/sj.gene.6363768
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2001
    detail.hit.zdb_id: 2006268-0
    SSG: 12
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