12 results on '"Henderson, Candace D."'
Search Results
2. Immunological Interaction of HLA-DPB1 and Proteinase 3 in ANCA Vasculitis is Associated with Clinical Disease Activity
- Author
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Chen, Dhruti P., McInnis, Elizabeth A., Wu, Eveline Y., Stember, Katherine G., Hogan, Susan L., Hu, Yichun, Henderson, Candace D., Blazek, Lauren N., Mallal, Simon, Karosiene, Edita, Peters, Bjoern, Sidney, John, James, Eddie A., Kwok, William W., Jennette, J. Charles, Ciavatta, Dominic J., Falk, Ronald J., and Free, Meghan E.
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- 2022
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3. Examining the role of patient-reported external factors and risk of relapse in anti-neutrophilic cytoplasmic autoantibody vasculitis.
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Collie, Mary M., Chen, Dhruti P., Yichun Hu, Blazek, Lauren N., Derebail, Vimal K., Wu, Eveline Y., Jain, Koyal, Orzechowski, Nicole, Poulton, Caroline J., Henderson, Candace D., Falk, Ronald J., and Hogan, Susan L.
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- 2024
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4. ANCA autoantigen gene expression highlights neutrophil heterogeneity where expression in normal-density neutrophils correlates with ANCA-induced activation
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Jones, Britta E., Herrera, Carolina A., Agosto-Burgos, Christian, Starmer, Joshua, Bass, William A., Poulton, Caroline J., Blazek, Lauren, Henderson, Candace D., Hu, Yichun, Hogan, Susan L., Hu, Peiqi, Xiao, Hong, Wu, Eveline Y., Chen, Dhruti P., Jennette, J. Charles, Free, Meghan E., Falk, Ronald J., and Ciavatta, Dominic J.
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- 2020
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5. The frequency of Treg subsets distinguishes disease activity in ANCA vasculitis.
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Agosto‐Burgos, Christian, Wu, Eveline Y, Iannone, Marie A, Hu, Yichun, Hogan, Susan L, Henderson, Candace D, Kennedy, Kristin B, Blazek, Lauren, Herrera, Carolina A, Munson, Dominique, Falk, Ronald J, Ciavatta, Dominic J, and Free, Meghan E
- Subjects
REGULATORY T cells ,AUTOIMMUNE diseases ,VASCULITIS ,T cells ,PREVENTIVE medicine ,DISEASE remission - Abstract
Objectives: T regulatory cells (Tregs) are a heterogeneous group of immunoregulatory cells that dampen self‐harming immune responses and prevent the development of autoimmune diseases. In anti‐neutrophil cytoplasmic autoantibody (ANCA) vasculitis, Tregs possess diminished suppressive capacity, which has been attributed to the expression of a FOXP3 splice‐variant lacking exon 2 in T cells (FOXP3Δ2 CD4+ T cells). However, the suppressive capacity of Tregs varies between subsets. We evaluated the frequency of Treg subsets in ANCA vasculitis as a potential explanation for diminished suppressive capacity. Methods: We developed a custom mass cytometry panel and performed deep immune profiling of Tregs in healthy controls, patients with active disease and in remission. Using these data, we performed multidimensional reduction and discriminant analysis to identify associations between Treg subsets and disease activity. Results: Total Tregs were expanded in ANCA vasculitis, which was associated with remission and the administration of rituximab and/or prednisone. The frequency of FOXP3Δ2 CD4+ T cells did not distinguish disease activity and this population had high expression levels of CD127 and lacked both CD25 and Helios, suggesting that they are not conventional Tregs. The frequency of CXCR3+, CD103+ and CCR7+ Tregs distinguished disease activity, and the combination of the frequency of these three Treg subsets segregated active patients from patients in remission and healthy controls. From these three subsets, the frequency of CXCR3+ Tregs distinguished patients with active disease with renal involvement. Conclusion: Treg heterogeneity can discriminate disease activity and should be explored as a biomarker of disease activity in ANCA vasculitis. [ABSTRACT FROM AUTHOR]
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- 2022
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6. Birth Weight Associated With Kidney Size in Middle-Aged Women
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Henderson, Candace D. and Sanderson, Keia R.
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- 2021
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7. Measuring Circulating Complement Activation Products in Myeloperoxidase– and Proteinase 3–Antineutrophil Cytoplasmic Antibody–Associated Vasculitis.
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Wu, Eveline Y., McInnis, Elizabeth A., Boyer‐Suavet, Sonia, Mendoza, Carmen E., Aybar, Lydia T., Kennedy, Kristin B., Poulton, Caroline J., Henderson, Candace D., Hu, Yichun, Hogan, Susan L., Hu, Peiqi, Xiao, Hong, Nachman, Patrick H., Jennette, J. Charles, Falk, Ronald J., and Bunch, Donna O.
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AUTOIMMUNE diseases ,COMPLEMENT (Immunology) ,ENZYME inhibitors ,ENZYME-linked immunosorbent assay ,ETHYLENEDIAMINETETRAACETIC acid ,PEROXIDASE ,PROTEOLYTIC enzymes ,STATISTICS ,VASCULITIS ,DATA analysis ,SYMPTOMS ,DISEASE remission ,SEROTYPES ,ANTINEUTROPHIL cytoplasmic antibodies - Abstract
Objective: There is accumulating evidence that complement activation is important in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) pathogenesis. This study was undertaken to investigate complement activation in AAV with myeloperoxidase (MPO) positivity and AAV with proteinase 3 (PR3) positivity after determining optimal methods for measuring activated complement factors in circulation. Methods: Participants included 98 patients with AAV (45 MPO‐ANCA positive, 53 PR3‐ANCA positive) and 35 healthy controls. Plasma was obtained from blood collected using EDTA tubes, with or without 100 μg/ml Futhan. Levels of Bb, C3a, C5a, soluble C5b–9 (sC5b–9), properdin, and C4d were measured by enzyme‐linked immunosorbent assay. Group comparisons were made using Wilcoxon's 2‐sample test. Paired data were analyzed using a matched pairs signed rank test. Results: Compared to healthy controls, certain complement analyte levels were high in patients with active AAV with MPO positivity, including C3a (P < 0.0001), C5a (P = 0.0004), and sC5b–9 (P = 0.0007). During remission, levels of Bb (P = 0.001), C3a (P < 0.0001), and sC5b–9 (P = 0.003) were higher. Compared to healthy controls, C3a (P < 0.0001), C5a (P = 0.002), sC5b–9 (P = 0.0001), and C4d (P = 0.005) levels were higher in patients with active AAV with PR3 positivity; levels of C3a (P < 0.0001) and C4d (P = 0.007) were also higher duriing remission. There were no significant differences in any complement analyte for either ANCA serotype between patients with active disease and those with disease in remission. Among patients with paired samples, sC5‐9 levels were significantly lower during disease remission compared to active disease. C5a was significantly lower among patients with disease in long‐term remission who were not receiving therapy. For Bb, C5a, and sC5b–9, median levels and individual values were considerably higher in control and patient samples processed without Futhan compared to those processed with Futhan. Conclusion: Complement activation occurs in both MPO‐positive AAV and PR3‐positive AAV. The complement activation profile differs according to disease activity and possibly ANCA serotype. Futhan reduces in vitro complement activation and provides a more accurate measurement. [ABSTRACT FROM AUTHOR]
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- 2019
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8. Immunoglobulins G from patients with ANCA-associated vasculitis are atypically glycosylated in both the Fc and Fab regions and the relation to disease activity.
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Lardinois, Olivier M., Deterding, Leesa J., Hess, Jacob J., Poulton, Caroline J., Henderson, Candace D., Jennette, J. Charles, Nachman, Patrick H., and Falk, Ronald J.
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IMMUNOGLOBULIN G ,VASCULITIS ,MYELOPEROXIDASE ,GLYCOSYLATION ,BLOOD plasma ,CLINICAL trials - Abstract
Background: Anti-neutrophil cytoplasmic autoantibodies (ANCA) directed against myeloperoxidase (MPO) and proteinase 3 (PR3) are pathogenic in ANCA-associated vasculitis (AAV). The respective role of IgG Fc and Fab glycosylation in mediating ANCA pathogenicity is incompletely understood. Herein we investigate in detail the changes in Fc and Fab glycosylation in MPO-ANCA and Pr3-ANCA and examine the association of glycosylation aberrancies with disease activity. Methodology: Total IgG was isolated from serum or plasma of a cohort of 30 patients with AAV (14 MPO-ANCA; 16 PR3-ANCA), and 19 healthy control subjects. Anti-MPO specific IgG was affinity-purified from plasma of an additional cohort of 18 MPO-ANCA patients undergoing plasmapheresis. We used lectin binding assays, liquid chromatography, and mass spectrometry-based methods to analyze Fc and Fab glycosylation, the degree of sialylation of Fc and Fab fragments and to determine the exact localization of N-glycans on Fc and Fab fragments. Principal findings: IgG
1 Fc glycosylation of total IgG was significantly reduced in patients with active AAV compared to controls. Clinical remission was associated with complete glycan normalization for PR3-ANCA patients but not for MPO-ANCA patients. Fc-glycosylation of anti-MPO specific IgG was similar to total IgG purified from plasma. A major fraction of anti-MPO specific IgG harbor extensive glycosylation within the variable domain on the Fab portion. Conclusions/Significance: Significant differences exist between MPO and PR3-ANCA regarding the changes in amounts and types of glycans on Fc fragment and the association with disease activity. These differences may contribute to significant clinical difference in the disease course observed between the two diseases. [ABSTRACT FROM AUTHOR]- Published
- 2019
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9. Histone modification signature at myeloperoxidase and proteinase 3 in patients with anti-neutrophil cytoplasmic autoantibody-associated vasculitis
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McInnis, Elizabeth A, Hogan, Susan, Jennette, Charles, Falk, Ronald J., Ge, Heng, Henderson, Candace D, Yang, Jiajin, Poulton, Caroline J, Jones, Britta E, Hu, Yichun, Ciavatta, Dominic, and Pendergraft, William F
- Subjects
3. Good health - Abstract
Background Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disease characterized by destructive vascular inflammation. Two prominent ANCA autoantigens are myeloperoxidase (MPO) and proteinase 3 (PR3), and transcription of MPO and PRTN3, the genes encoding the autoantigens, is associated with disease activity. We investigated whether patients with AAV have alterations in histone modifications, particularly those associated with transcriptional activation, at MPO and PRTN3. Results We identified a network of genes regulating histone modifications that were differentially expressed in AAV patients compared to healthy controls. We focused on four genes (EHMT1 and EHMT2, ING4, and MSL1) and found their expression correlated with expression of MPO and PRTN3. Methylation of histone H3K9, catalyzed by EHMT1 and EHMT2 and associated with gene silencing, was most depleted at MPO and PRTN3 in patients with active disease and the highest MPO and PRTN3 expression. Acetylation of histone H4K16, modified by complexes containing ING4 and MSL1 and associated with gene activation, was most enriched at MPO and PRTN3 in patients with active disease and the highest MPO and PRTN3 expression. Methylation at H3K4, a mark of transcriptional activation, was enriched at MPO and PRTN3 in patients and healthy controls. Conclusions MPO and PRTN3 in neutrophils of AAV patients with active disease have a distinct pattern of histone modifications, which implicates epigenetic mechanisms in regulating expression of autoantigen genes and suggests that the epigenome may be involved in AAV pathogenesis.
10. Infection-Related Acute Care Events among Patients with Glomerular Disease.
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Glenn DA, Henderson CD, O'Shaughnessy M, Hu Y, Bomback A, Gibson K, Greenbaum LA, Zee J, Mariani L, Falk R, Hogan S, and Mottl A
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- Acute Disease, Adolescent, Adrenal Cortex Hormones therapeutic use, Adult, Age Factors, Child, Communicable Diseases diagnosis, Europe epidemiology, Female, Glomerulonephritis, IGA diagnosis, Glomerulonephritis, IGA drug therapy, Glomerulonephritis, Membranous diagnosis, Glomerulonephritis, Membranous drug therapy, Glomerulosclerosis, Focal Segmental diagnosis, Glomerulosclerosis, Focal Segmental drug therapy, Humans, Incidence, Male, Middle Aged, Nephrosis, Lipoid diagnosis, Nephrosis, Lipoid drug therapy, North America epidemiology, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, Young Adult, Communicable Diseases epidemiology, Communicable Diseases therapy, Emergency Service, Hospital, Glomerulonephritis, IGA epidemiology, Glomerulonephritis, Membranous epidemiology, Glomerulosclerosis, Focal Segmental epidemiology, Hospitalization, Nephrosis, Lipoid epidemiology
- Abstract
Background and Objectives: Infections contribute to patient morbidity and mortality in glomerular disease. We sought to describe the incidence of, and identify risk factors for, infection-related acute care events among Cure Glomerulonephropathy Network (CureGN) study participants., Design, Setting, Participants, & Measurements: CureGN is a prospective, multicenter, cohort study of children and adults with biopsy sample-proven minimal change disease, FSGS, membranous nephropathy, or IgA nephropathy/vasculitis. Risk factors for time to first infection-related acute care events (hospitalization or emergency department visit) were identified using multivariable Cox proportional hazards regression., Results: Of 1741 participants (43% female, 41% <18 years, 68% White), 163 (9%) experienced infection-related acute care events over a median follow-up of 17 months (interquartile range, 9-26 months). Unadjusted incidence rates of infection-related acute care events were 13.2 and 6.2 events per 100 person-years among pediatric and adult participants, respectively. Among participants with versus without corticosteroid exposure at enrollment, unadjusted incidence rates were 50.6 and 28.6 per 100 person-years, respectively, during the first year of follow-up (adjusted hazard ratio for time to first infection, 1.31; 95% CI, 0.89 to 1.93), and 4.1 and 1.1 per 100 person-years, respectively, after 1 year of follow-up (hazard ratio, 2.99; 95% CI, 1.54 to 5.79). Hypoalbuminemia combined with nephrotic-range proteinuria (serum albumin ≤2.5 g/dl and urinary protein-creatinine ratio >3.5 mg/mg), compared with serum albumin >2.5 g/dl and urinary protein-creatinine ratio ≤3.5 mg/mg, was associated with higher risk of time to first infection (adjusted hazard ratio, 2.49; 95% CI, 1.51 to 4.12)., Conclusions: Among CureGN participants, infection-related acute care events were common and associated with younger age, corticosteroid exposure, and hypoalbuminemia with proteinuria., (Copyright © 2020 by the American Society of Nephrology.)
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- 2020
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11. Gene-Specific DNA Methylation Changes Predict Remission in Patients with ANCA-Associated Vasculitis.
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Jones BE, Yang J, Muthigi A, Hogan SL, Hu Y, Starmer J, Henderson CD, Poulton CJ, Brant EJ, Pendergraft WF 3rd, Jennette JC, Falk RJ, and Ciavatta DJ
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- Female, Gene Expression Regulation, Humans, Male, Middle Aged, Prognosis, Remission Induction, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis genetics, Autoantigens genetics, DNA Methylation, Myeloblastin genetics, Peroxidase genetics
- Abstract
ANCA-associated vasculitis is an autoimmune condition characterized by vascular inflammation and organ damage. Pharmacologically induced remission of this condition is complicated by relapses. Potential triggers of relapse are immunologic challenges and environmental insults, both of which associate with changes in epigenetic silencing modifications. Altered histone modifications implicated in gene silencing associate with aberrant autoantigen expression. To establish a link between DNA methylation, a model epigenetic gene silencing modification, and autoantigen gene expression and disease status in ANCA-associated vasculitis, we measured gene-specific DNA methylation of the autoantigen genes myeloperoxidase ( MPO ) and proteinase 3 ( PRTN3 ) in leukocytes of patients with ANCA-associated vasculitis observed longitudinally ( n =82) and of healthy controls ( n =32). Patients with active disease demonstrated hypomethylation of MPO and PRTN3 and increased expression of the autoantigens; in remission, DNA methylation generally increased. Longitudinal analysis revealed that patients with ANCA-associated vasculitis could be divided into two groups, on the basis of whether DNA methylation increased or decreased from active disease to remission. In patients with increased DNA methylation, MPO and PRTN3 expression correlated with DNA methylation. Kaplan-Meier estimate of relapse revealed patients with increased DNA methylation at the PRTN3 promoter had a significantly greater probability of a relapse-free period ( P <0.001), independent of ANCA serotype. Patients with decreased DNA methylation at the PRTN3 promoter had a greater risk of relapse (hazard ratio, 4.55; 95% confidence interval, 2.09 to 9.91). Thus, changes in the DNA methylation status of the PRTN3 promoter may predict the likelihood of stable remission and explain autoantigen gene regulation., (Copyright © 2017 by the American Society of Nephrology.)
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- 2017
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12. Histone modification signature at myeloperoxidase and proteinase 3 in patients with anti-neutrophil cytoplasmic autoantibody-associated vasculitis.
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Yang J, Ge H, Poulton CJ, Hogan SL, Hu Y, Jones BE, Henderson CD, McInnis EA, Pendergraft WF 3rd, Jennette JC, Falk RJ, and Ciavatta DJ
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- Acylation, Epigenesis, Genetic, Gene Expression Profiling methods, Gene Expression Regulation, Humans, Methylation, Oligonucleotide Array Sequence Analysis methods, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis genetics, Gene Regulatory Networks, Histones metabolism, Myeloblastin genetics, Peroxidase genetics
- Abstract
Background: Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disease characterized by destructive vascular inflammation. Two prominent ANCA autoantigens are myeloperoxidase (MPO) and proteinase 3 (PR3), and transcription of MPO and PRTN3 , the genes encoding the autoantigens, is associated with disease activity. We investigated whether patients with AAV have alterations in histone modifications, particularly those associated with transcriptional activation, at MPO and PRTN3 ., Results: We identified a network of genes regulating histone modifications that were differentially expressed in AAV patients compared to healthy controls. We focused on four genes ( EHMT1 and EHMT2 , ING4 , and MSL1 ) and found their expression correlated with expression of MPO and PRTN3 . Methylation of histone H3K9, catalyzed by EHMT1 and EHMT2 and associated with gene silencing, was most depleted at MPO and PRTN3 in patients with active disease and the highest MPO and PRTN3 expression. Acetylation of histone H4K16, modified by complexes containing ING4 and MSL1 and associated with gene activation, was most enriched at MPO and PRTN3 in patients with active disease and the highest MPO and PRTN3 expression. Methylation at H3K4, a mark of transcriptional activation, was enriched at MPO and PRTN3 in patients and healthy controls., Conclusions: MPO and PRTN3 in neutrophils of AAV patients with active disease have a distinct pattern of histone modifications, which implicates epigenetic mechanisms in regulating expression of autoantigen genes and suggests that the epigenome may be involved in AAV pathogenesis.
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- 2016
- Full Text
- View/download PDF
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