4 results on '"Maksimowicz‐McKinnon, Kathleen"'
Search Results
2. CD4+CD28+KIR+CD11a hi T cells correlate with disease activity and are characterized by a pro-inflammatory epigenetic and transcriptional profile in lupus patients.
- Author
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Gensterblum E, Renauer P, Coit P, Strickland FM, Kilian NC, Miller S, Ognenovski M, Wren JD, Tsou PS, Lewis EE, Maksimowicz-McKinnon K, McCune WJ, Richardson BC, and Sawalha AH
- Subjects
- CD11a Antigen metabolism, CD28 Antigens metabolism, CD4 Antigens metabolism, Cells, Cultured, DNA Methylation, Disease Progression, Epigenesis, Genetic, Female, Genetic Profile, Humans, Immunophenotyping, Lupus Erythematosus, Systemic diagnosis, Lupus Erythematosus, Systemic epidemiology, Receptors, KIR metabolism, Risk, Sequence Analysis, RNA, United States epidemiology, Black or African American, Inflammation immunology, Lupus Erythematosus, Systemic immunology, T-Lymphocyte Subsets immunology, T-Lymphocytes immunology
- Abstract
Objective: The goal of this study was to comprehensively characterize CD4+CD28+ T cells overexpressing CD11a and KIR genes, and examine the relationship between this T cell subset, genetic risk, and disease activity in lupus., Methods: The size of the CD4+CD28+KIR+CD11a
hi T cell subset was determined by flow cytometry, and total genetic risk for lupus was calculated in 105 female patients using 43 confirmed genetic susceptibility loci. Primary CD4+CD28+KIR+CD11ahi T cells were isolated from lupus patients or were induced from healthy individuals using 5-azacytidine. Genome-wide DNA methylation was analyzed using an array-based approach, and the transcriptome was assessed by RNA sequencing. Transcripts in the CDR3 region were used to assess the TCR repertoire. Chromatin accessibility was determined using ATAC-seq., Results: A total of 31,019 differentially methylated sites were identified in induced KIR+CD11ahi T cells with >99% being hypomethylated. RNA sequencing revealed a clear pro-inflammatory transcriptional profile. TCR repertoire analysis suggests less clonotype diversity in KIR+CD11ahi compared to autologous KIR-CD11alow T cells. Similarly, primary KIR+CD11ahi T cells isolated from lupus patients were hypomethylated and characterized by a pro-inflammatory chromatin structure. We show that the genetic risk for lupus was significantly higher in African-American compared to European-American lupus patients. The demethylated CD4+CD28+KIR+CD11ahi T cell subset size was a better predictor of disease activity in young (age ≤ 40) European-American patients independent of genetic risk., Conclusion: CD4+CD28+KIR+CD11ahi T cells are demethylated and characterized by pro-inflammatory epigenetic and transcriptional profiles in lupus. Eliminating these cells or blocking their pro-inflammatory characteristics might present a novel therapeutic approach for lupus., (Copyright © 2017 Elsevier Ltd. All rights reserved.)- Published
- 2018
- Full Text
- View/download PDF
3. Distribution of arterial lesions in Takayasu's arteritis and giant cell arteritis.
- Author
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Grayson PC, Maksimowicz-McKinnon K, Clark TM, Tomasson G, Cuthbertson D, Carette S, Khalidi NA, Langford CA, Monach PA, Seo P, Warrington KJ, Ytterberg SR, Hoffman GS, and Merkel PA
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Axillary Artery pathology, Canada epidemiology, Carotid Arteries pathology, Child, Cluster Analysis, Comorbidity, Female, Giant Cell Arteritis epidemiology, Humans, Male, Mesenteric Arteries pathology, Middle Aged, Takayasu Arteritis epidemiology, United States epidemiology, Young Adult, Aorta pathology, Giant Cell Arteritis pathology, Takayasu Arteritis pathology
- Abstract
Objectives: To compare patterns of arteriographic lesions of the aorta and primary branches in patients with Takayasu's arteritis (TAK) and giant cell arteritis (GCA)., Methods: Patients were selected from two North American cohorts of TAK and GCA. The frequency of arteriographic lesions was calculated for 15 large arteries. Cluster analysis was used to derive patterns of arterial disease in TAK versus GCA and in patients categorised by age at disease onset. Using latent class analysis, computer derived classification models based upon patterns of arterial disease were compared with traditional classification., Results: Arteriographic lesions were identified in 145 patients with TAK and 62 patients with GCA. Cluster analysis demonstrated that arterial involvement was contiguous in the aorta and usually symmetric in paired branch vessels for TAK and GCA. There was significantly more left carotid (p=0.03) and mesenteric (p=0.02) artery disease in TAK and more left and right axillary (p<0.01) artery disease in GCA. Subclavian disease clustered asymmetrically in TAK and in patients ≤55 years at disease onset and clustered symmetrically in GCA and patients >55 years at disease onset. Computer derived classification models distinguished TAK from GCA in two subgroups, defining 26% and 18% of the study sample; however, 56% of patients were classified into a subgroup that did not strongly differentiate between TAK and GCA., Conclusions: Strong similarities and subtle differences in the distribution of arterial disease were observed between TAK and GCA. These findings suggest that TAK and GCA may exist on a spectrum within the same disease.
- Published
- 2012
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- View/download PDF
4. Poor 1-year outcomes after percutaneous coronary interventions in systemic lupus erythematosus: report from the National Heart, Lung, and Blood Institute Dynamic Registry.
- Author
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Maksimowicz-McKinnon K, Selzer F, Manzi S, Kip KE, Mulukutla SR, Marroquin OC, Smitherman TC, Kuller LH, Williams DO, and Wasko MC
- Subjects
- Coronary Artery Disease epidemiology, Diabetes Mellitus epidemiology, Female, Humans, Hypertension epidemiology, Male, Middle Aged, Myocardial Infarction epidemiology, Prospective Studies, Registries, Retreatment, Smoking epidemiology, United States epidemiology, Angioplasty, Balloon, Coronary, Coronary Artery Disease therapy, Lupus Erythematosus, Systemic epidemiology
- Abstract
Background: Women with systemic lupus erythematosus (SLE) have premature and accelerated atherosclerosis. Although percutaneous coronary intervention (PCI) is used frequently to treat coronary artery disease in SLE, little is known regarding PCI outcomes immediately after PCI and after discharge., Methods and Results: Baseline demographic, procedure-related, and adverse outcome data on consecutive patients undergoing PCI during 5 recruitment "waves" of the National Heart, Lung, and Blood Institute Dynamic Registry across 23 clinical centers were collected. SLE patients (n=28) were compared with non-SLE patients (n=3385). SLE patients were younger and more often female in comparison with non-SLE patients undergoing PCI. SLE patients were less likely than non-SLE patients to have hyperlipidemia but had a similar prevalence of hypertension, diabetes mellitus, and tobacco use. The prevalence of multivessel disease was similar between groups. Initial intervention success (by angiographic definition) was not significantly different between groups. At 1 year, SLE patients were more likely to experience a myocardial infarction (15.6% versus 4.8%, P=0.01) and more often required repeat PCI (31.3% versus 11.8%, P=0.009) than non-SLE patients, even after adjustment for important covariates., Conclusions: SLE patients had significantly worse cardiovascular outcomes at 1 year than non-SLE patients. Even considering the small number of SLE patients, these differences were striking. Further study is warranted to explore other factors potentially accounting for this disparity, including SLE disease activity and duration, presence of hypercoagulable state, and immunosuppressive therapy.
- Published
- 2008
- Full Text
- View/download PDF
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