Person: Costenbader, Karen
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Costenbader
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Karen
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Costenbader, Karen
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Publication Anti-citrullinated peptide autoantibodies, human leukocyte antigen shared epitope and risk of future rheumatoid arthritis: a nested case–control study(BioMed Central, 2013) Arkema, Elizabeth V; Goldstein, Barbara L; Robinson, William; Sokolove, Jeremy; Wagner, Catriona A; Malspeis, Susan; Rosner, Bernard; Grodstein, Francine; Karlson, Elizabeth; Costenbader, KarenIntroduction: The aim of this study was to characterize anti-citrullinated peptide antibody (ACPA) serostatus in pre-clinical rheumatoid arthritis (RA) with and without Human Leukocyte Antigen-Shared Epitope (HLA-SE) alleles. Methods: We identified 192 women in the Nurses’ Health Study cohorts with blood samples obtained 4 months to 17 years prior to medical record-confirmed RA diagnosis. Three controls were selected matched on age, cohort, menopausal status and post-menopausal hormone use. Reactivities to 18 ACPAs were measured using a custom BioPlex platform. We used conditional logistic regression to calculate the relative risk (RR) of RA for any ACPA-positive and peptide-specific ACPA-positive and examined RRs by time between blood draw and RA onset. Measures of multiplicative and additive interaction between any ACPA-positive and HLA-SE were calculated. Results: All ACPAs by peptide groups were significantly associated with RA risk, RRs ranged from 4.7 to 11.7. The association between ACPA and RA varied over time with the strongest association in those with blood draw less than 5 years before onset (RR 17.0 [95% CI 5.8 to 53.7]) and no association 10 or more years prior to onset (RR 1.4 [95% CI 0.5 to 4.3]). Individuals with both HLA-SE and any ACPA-positive had the highest risk of RA. HLA-SE-positive RA cases showed reactivity to more ACPA types than HLA-SE negative (χ2 test for trend, P = 0.01). Conclusions: There is increasing ACPA reactivity up to 10 years before RA onset with the strongest association within 5 years of RA onset. The magnitude of the response to ACPAs, in combination with the presence of HLA-SE, is most important for identifying those individuals with the highest risk of RA.Publication Erythropoiesis-stimulating Agent Use among Patients with Lupus Nephritis Approaching End-stage Renal Disease(2013) Gómez-Puerta, José A; Waikar, Sushrut; Solomon, Daniel; Liu, Jun; Alarcón, Graciela S; Winkelmayer, Wolfgang C; Costenbader, KarenObjectives: Little is known about erythropoiesis-stimulating agents (ESAs) utilization among lupus nephritis (LN) patients with incipient ESRD. We aimed to identify sociodemographic and clinical factors associated with ESA use among incident LN ESRD patients. Methods: Among all individuals age ≥18 with incident ESRD from 1995-2008 in the U.S. Renal Data System (USRDS), we identified those with systemic lupus erythematosus (ICD-9 code 710.0) as the cause of ESRD. ESA use at ESRD onset was ascertained from the Medical Evidence Report. Year of onset, age, sex, race/ethnicity, medical insurance, employment status, residential region, clinical factors and comorbidities were considered potentially associated with ESA use in multivariable-adjusted logistic regression analyses. Results: We identified 12,533 individuals with incident LN ESRD (1% of entire population). Of those, 4,288 (34%) received an ESA preceding ESRD. In multivariable-adjusted models, ESA users had higher serum albumin and hemoglobin concentrations, were more likely to be women, and to live in the Northeast. Conversely, Medicaid beneficiaries, the uninsured, unemployed, African Americans, Hispanics, and those with IV drug use, congestive heart failure and obesity had lower ESA use. Conclusion: Among all U.S. patients and those with LN who developed ESRD, approximately one third received ESAs. Patient sex, race, age, medical insurance, residential region and clinical factors were significantly associated with ESA therapy. While there are no guidelines for ESA use in LN patients approaching ESRD, there has been wide sociodemographic variation, raising questions about ESA prescription practices.Publication Altered expression of protein tyrosine phosphatase, non-receptor type 22 isoforms in systemic lupus erythematosus(BioMed Central, 2014) Chang, Hui-Hsin; Tseng, William; Cui, Jing; Costenbader, Karen; Ho, I-ChengIntroduction: A C-to-T single nucleotide polymorphism (SNP) located at position 1858 of human protein tyrosine phosphatase, non-receptor type 22 (PTPN22) complementary DNA (cDNA) is associated with an increased risk of systemic lupus erythematosus (SLE). How the overall activity of PTPN22 is regulated and how the expression of PTPN22 differs between healthy individuals and patients with lupus are poorly understood. Our objectives were to identify novel alternatively spliced forms of PTPN22 and to examine the expression of PTPN22 isoforms in healthy donors and patients with lupus. Methods: Various human PTPN22 isoforms were identified from the GenBank database or amplified directly from human T cells. The expression of these isoforms in primary T cells and macrophages was examined with real-time polymerase chain reaction. The function of the isoforms was determined with luciferase assays. Blood samples were collected from 49 subjects with SLE and 15 healthy controls. Correlation between the level of PTPN22 isoforms in peripheral blood and clinical features of SLE was examined with statistical analyses. Results: Human PTPN22 was expressed in several isoforms, which differed in their level of expression and subcellular localization. All isoforms except one were functionally interchangeable in regulating NFAT activity. SLE patients expressed higher levels of PTPN22 than healthy individuals and the levels of PTPN22 were negatively correlated with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC-DI). Conclusions: The overall activity of PTPN22 is determined by the functional balance among all isoforms. The levels of PTPN22 isoforms in peripheral blood could represent a useful biomarker of SLE.Publication Administrative Algorithms to identify Avascular necrosis of bone among patients undergoing upper or lower extremity magnetic resonance imaging: a validation study(BioMed Central, 2017) Barbhaiya, Medha; Dong, Yan; Sparks, Jeffrey; Losina, Elena; Costenbader, Karen; Katz, JeffreyBackground: Studies of the epidemiology and outcomes of avascular necrosis (AVN) require accurate case-finding methods. The aim of this study was to evaluate performance characteristics of a claims-based algorithm designed to identify AVN cases in administrative data. Methods: Using a centralized patient registry from a US academic medical center, we identified all adults aged ≥18 years who underwent magnetic resonance imaging (MRI) of an upper/lower extremity joint during the 1.5 year study period. A radiologist report confirming AVN on MRI served as the gold standard. We examined the sensitivity, specificity, positive predictive value (PPV) and positive likelihood ratio (LR+) of four algorithms (A-D) using International Classification of Diseases, 9th edition (ICD-9) codes for AVN. The algorithms ranged from least stringent (Algorithm A, requiring ≥1 ICD-9 code for AVN [733.4X]) to most stringent (Algorithm D, requiring ≥3 ICD-9 codes, each at least 30 days apart). Results: Among 8200 patients who underwent MRI, 83 (1.0% [95% CI 0.78–1.22]) had AVN by gold standard. Algorithm A yielded the highest sensitivity (81.9%, 95% CI 72.0–89.5), with PPV of 66.0% (95% CI 56.0–75.1). The PPV of algorithm D increased to 82.2% (95% CI 67.9–92.0), although sensitivity decreased to 44.6% (95% CI 33.7–55.9). All four algorithms had specificities >99%. Conclusion: An algorithm that uses a single billing code to screen for AVN among those who had MRI has the highest sensitivity and is best suited for studies in which further medical record review confirming AVN is feasible. Algorithms using multiple billing codes are recommended for use in administrative databases when further AVN validation is not feasible.Publication Rheumatoid Arthritis in Agricultural Health Study Spouses: Associations with Pesticides and Other Farm Exposures(National Institute of Environmental Health Sciences, 2016) Parks, Christine G.; Hoppin, Jane A.; De Roos, Anneclaire J.; Costenbader, Karen; Alavanja, Michael C.; Sandler, Dale P.Background: Farming has been associated with rheumatoid arthritis (RA), but the role of pesticides is not known. Objectives: We examined associations between RA and pesticides or other agricultural exposures among female spouses of licensed pesticide applicators in the Agricultural Health Study. Methods: Women were enrolled between 1993 and 1997 and followed through 2010. Cases (n = 275 total, 132 incident), confirmed by a physician or by self-reported use of disease modifying antirheumatic drugs, were compared with noncases (n = 24,018). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models adjusted for age, state, and smoking pack-years. Results: Overall, women with RA were somewhat more likely to have reported lifetime use of any specific pesticide versus no pesticides (OR = 1.4; 95% CI: 1.0, 1.6). Of the 15 pesticides examined, maneb/mancozeb (OR = 3.3; 95% CI: 1.5, 7.1) and glyphosate (OR = 1.4; 95% CI: 1.0, 2.1) were associated with incident RA compared with no pesticide use. An elevated, but non-statistically significant association with incident RA was seen for DDT (OR = 1.9; 95% CI: 0.97, 3.6). Incident RA was also associated with the application of chemical fertilizers (OR = 1.7; 95% CI: 1.1, 2.7) and cleaning with solvents (OR = 1.6; 95% CI: 1.1, 2.4), but inversely associated with lifetime livestock exposure as a child and adult (OR = 0.48; 95% CI: 0.24, 0.97) compared with no livestock exposure. Conclusions: Our results suggest that specific agricultural pesticides, solvents, and chemical fertilizers may increase the risk of RA in women, while exposures involving animal contact may be protective. Citation: Parks CG, Hoppin JA, De Roos AJ, Costenbader KH, Alavanja MC, Sandler DP. 2016. Rheumatoid arthritis in Agricultural Health Study spouses: associations with pesticides and other farm exposures. Environ Health Perspect 124:1728–1734; http://dx.doi.org/10.1289/EHP129Publication Response to “Comment on ‘Rheumatoid Arthritis in Agricultural Health Study Spouses: Associations with Pesticides and Other Farm Exposures’”(National Institute of Environmental Health Sciences, 2016) Parks, Christine G.; Hoppin, Jane A.; De Roos, Anneclaire J.; Costenbader, Karen; Sandler, Dale P.Publication Dietary intake of vitamin D during adolescence and risk of adult onset systemic lupus erythematosus and rheumatoid arthritis(BioMed Central, 2012) Hiraki, Linda T.; Costenbader, Karen; Munger, Kassandra; Karlson, ElizabethPublication Prevalence and demographics of systemic lupus erythematosus and lupus nephritis among US children with Medicaid coverage, 2002-2004(BioMed Central, 2012) Hiraki, Linda T.; Shaykevich, Tamara; Winkelmayer, Wolfgang C; Costenbader, KarenPublication Epstein–Barr Virus and Rheumatoid Arthritis: Is There a Link?(BioMed Central, 2006) Costenbader, Karen; Karlson, ElizabethRheumatoid arthritis is a systemic autoimmune disease characterized by chronic, destructive, debilitating arthritis. Its etiology is unknown; it is presumed that environmental factors trigger development in the genetically predisposed. Epstein–Barr virus, a nearly ubiquitous virus in the human population, has generated great interest as a potential trigger. This virus stimulates polyclonal lymphocyte expansion and persists within B lymphocytes for the host's life, inhibited from reactivating by the immune response. In latent and replicating forms, it has immunomodulating actions that could play a role in the development of this autoimmune disease. The evidence linking Epstein–Barr virus and rheumatoid arthritis is reviewed.Publication Practical and Theoretical Barriers to the Prevention of Accelerated Atherosclerosis in Systemic Lupus Erythematosus(BioMed Central, 2003) Costenbader, Karen; Liang, MatthewAccelerated atherosclerotic vascular disease (ASVD) is a major cause of death in systemic lupus erythematosus (SLE). Although many authorities are calling for aggressive assessment and management of cardiac risk factors in patients with SLE, both theoretical and practical barriers to this approach exist. It seems that SLE and/or its treatment are themselves strong risk factors for the development of ASVD and it is unclear how much this risk can be decreased by the control of traditional risk factors. Studies from several centers have shown that suboptimal risk factor management and barriers to acceptance of these measures must also be studied further.