Search

Your search keyword '"David A Hafler"' showing total 68 results
Start Over Author "David A Hafler" Journal clinical immunology
68 results on '"David A Hafler"'

1. Biomarkers in multiple sclerosis

Author

David A. Hafler, William J. Housley, and David Pitt

Subjects
Multiple Sclerosis, Multiple sclerosis, Immunology, Neurodegeneration, Brain, Disease, Biology, Antibodies, Viral, medicine.disease, JC Virus, Magnetic Resonance Imaging, Sensitivity and Specificity, Radiography, MicroRNAs, Immunoglobulin G, medicine, Humans, Immunology and Allergy, Biomarker (medicine), Microbiome, Biomarker discovery, CXCL13, CD163, Biomarkers
Abstract

Substantial effort has been made over the last six decades to identify biomarkers for multiple sclerosis that can improve disease diagnosis, predict disease progression, and improve clinical outcomes. However, to date, few of these findings have proven clinically useful. In this review, we address the current state of MS biomarker research. We start by discussing biomarkers currently in clinical use including Oligoclonal bands, MRI, and JC viral titers. We go on to discuss other potential biomarkers from MS serum and cerebrospinal fluid including Markers of neurodegeneration including neurofilament and GFAP, the monocyte macrophage marker CD163, the glial activation marker YKL-40, the B cell chemoattractant CXCL13, miRNA and mRNA, myelin reactive t cells, Kir4.1 antibodies, osteopontin, and microbiome associated lipopeptides. Finally, we discuss the current state of MS genetic studies and how genetics may offer simple, reliable testing for MS susceptibility and progression.

Published
2015
Full Text
View/download PDF

2. Functional analysis of highly defined, FACS-isolated populations of human regulatory CD4CD25 T cells

Author

Elizabeth Wolf, Clare Baecher-Allan, and David A. Hafler

Subjects
CD4-Positive T-Lymphocytes, Immunology, Enzyme-Linked Immunosorbent Assay, chemical and pharmacologic phenomena, Streptamer, Biology, Immunophenotyping, Interleukin 21, Antigens, CD, T-Lymphocyte Subsets, Receptors, Transferrin, Humans, Immunology and Allergy, Cytotoxic T cell, IL-2 receptor, L-Selectin, Antigen-presenting cell, Interleukin 3, Receptors, Interleukin-2, hemic and immune systems, CD58 Antigens, Flow Cytometry, Natural killer T cell, Coculture Techniques, Cell biology, Antigens, Differentiation, B-Lymphocyte, Immunoglobulin G, Interleukin 12, Leukocyte Common Antigens
Abstract

The importance of CD4+ CD25+ regulatory T cells (Treg) in maintaining immune homeostasis has been directly demonstrated in vivo by their manipulation in a number of autoimmune disease models in the mouse. In the study of human regulatory cells, we have found that the cells that consistently demonstrate the in vitro regulatory activity most similar to that described for murine cells in vitro are best identified by restricting the isolation of CD25+ CD4 T cells to those cells expressing only the highest levels of CD25, representing approximately 2-3% of total CD4 T cells. Thus, it is the CD4+ CD25high subset that exhibits the in vitro characteristics that are identical to the CD4+ CD25+ regulatory cells initially characterized in mice. Furthermore, the cells expressing medium to low levels of CD25 not only do not exhibit suppressive activity directly ex vivo, but also actually contain a significant proportion of CD62L- CD4 T cells which are believed to be in vivo activated T cells. Due to the inherent difficulties in using CD25 as a marker for the purification of Treg cells, the finding that selection of the CD25high subset of CD4+ CD25+ T cells minimizes the co-isolation of contaminating activated CD4 T cells is important for future studies of these Treg cells in human disease. In order to perform these studies, we first had to establish a highly reproducible 'micro in vitro co-culture' assay system to enable the functional analysis of high-purity, but low-yield regulatory populations derived from FACS sorting. With this system in place, we are poised to dissect the potential heterogeneity of mechanisms employed by highly specific subpopulations of CD4+ CD25+ cells.

Published
2005
Full Text
View/download PDF

3. In vitro evidence that subcutaneous administration of glatiramer acetate induces hyporesponsive T cells in patients with multiple sclerosis

Author

Jeffrey I. Krieger, Mascha C. Schmied, Christina Trollmo, Petra W. Duda, and David A. Hafler

Subjects
Adult, Male, medicine.medical_specialty, Injections, Subcutaneous, T-Lymphocytes, T cell, Immunology, Multiple Sclerosis, Relapsing-Remitting, Antigen, In vivo, Internal medicine, Immune Tolerance, Humans, Immunology and Allergy, Medicine, Glatiramer acetate, Antigen Presentation, Dose-Response Relationship, Drug, business.industry, Multiple sclerosis, T-cell receptor, Peripheral tolerance, Glatiramer Acetate, T lymphocyte, medicine.disease, Recombinant Proteins, Endocrinology, medicine.anatomical_structure, Cytokines, Interleukin-2, Female, Peptides, business, medicine.drug
Abstract

Glatiramer acetate (GA; Copaxone) is a random sequence polypeptide used in the treatment of relapsing remitting multiple sclerosis (RR MS). We have recently demonstrated that prior to treatment, GA induces proliferation of resting T cells and is not cross-reactive with myelin antigens. Daily GA injections induce a significant loss of this GA responsiveness, which is associated with the induction of highly cross-reactive Th2-type T cells potentially capable of suppressing inflammatory responses. The mechanism of action by which GA induces T cell nonresponsiveness leading to T cell receptor degeneracy in patients with RR MS is unknown. Here, we examined the effects of daily GA administration on the induction of T cell hyporesponsiveness. The frequency of GA-reactive T cells in peripheral blood of seven patients with RR MS was measured by limiting dilution analysis prior to and during 6 months of treatment. In addition, a model in which GA-reactive T cells were stimulated in vitro was developed to better characterize the selection of T cell populations over time. In vivo treatment with GA induced a decrease in GA-reactive T cell frequencies and hyporesponsiveness of CD4+ T cell reactivity to GA in vitro that was only partially reversed by the addition of IL-2. These data suggest that T cell peripheral tolerance to GA was achieved in vivo during treatment. Thus, our in vitro data suggest that the underlying changes in GA-reactive CD4+ T cell reactivity could be explained by the induction of T cell anergy and clonal elimination.

Published
2003
Full Text
View/download PDF

4. Decreases in Interleukin-4 Secretion by Invariant CD4−CD8−Vα24JαQ T Cells in Peripheral Blood of Patients with Relapsing–Remitting Multiple Sclerosis

Author

David A. Hafler, Rudolf Gausling, and Christina Trollmo

Subjects
Adult, CD4-Positive T-Lymphocytes, Male, medicine.medical_specialty, medicine.medical_treatment, T cell, Immunology, Alpha (ethology), CD8-Positive T-Lymphocytes, Biology, Multiple Sclerosis, Relapsing-Remitting, Immune system, Internal medicine, medicine, Humans, Immunology and Allergy, Interleukin 4, Middle Aged, Natural killer T cell, Clone Cells, Endocrinology, Cytokine, medicine.anatomical_structure, Cytokine secretion, Interleukin-4, CD8
Abstract

The cytokine profile of invariant CD4(-)CD8(-)V alpha 24J alpha Q T cells from patients with multiple sclerosis (MS) was compared with that of healthy controls. CD4(-)CD8(-)V alpha 24(+) T cells from the peripheral blood of 12 patients with relapsing-remitting MS (RR-MS), 5 patients with progressive MS (CP-MS), and 9 control individuals were directly sorted into single wells and expanded in vitro for analysis of IL-4 and IFN-gamma secretion; 315 V alpha 24J alpha Q T cell clones were generated and their T cell receptor (TCR) sequenced. T cell functionality was determined by examining cytokine secretion upon TCR cross-linking. RR-MS patients exhibited lower frequencies of IL-4 secreting CD4(-)CD8(-)V alpha 24J alpha Q T cell clones than patients with CP-MS and controls. No differences in IFN-gamma secretion were observed between the groups. An IL-4 positive cytokine profile could be correlated to the cloning efficiency of the V alpha 24J alpha Q T cells. We conclude that alterations in cytokine secretion patterns of CD4(-)CD8(-)V alpha 24J alpha Q T cells may influence the immune system and thus contribute to relapsing-remitting MS.

Published
2001
Full Text
View/download PDF

8. OR.43. Comparative Analysis of B Cell Repertoires Among Lesions and Normal Appearing White Matter in the Multiple Sclerosis Central Nervous System

Author

Scott J. Rodig, Laura Lovato, Kevin C. O’Connor, Simon N. Willis, David A. Hafler, and Stefany Almendinger

Subjects
White matter, Pathology, medicine.medical_specialty, medicine.anatomical_structure, Multiple sclerosis, Immunology, Central nervous system, medicine, Immunology and Allergy, Biology, medicine.disease, B cell
Published
2009
Full Text
View/download PDF

9. S.67. Detection of Myelin Reactive CD4+Cells in the Peripheral Blood of Patients with Multiple Sclerosis using MHC Class II Tetramers

Author

David A. Hafler, Kasia Bourcier, Junbao Yang, Vicki Seyfert-Margolis, William W. Kwok, Elizabeth M. Bradshaw, Khadir Raddassi, and Sally C. Kent

Subjects
MHC class II, biology, business.industry, Multiple sclerosis, Immunology, medicine.disease, Peripheral blood, Myelin, medicine.anatomical_structure, medicine, biology.protein, Immunology and Allergy, business
Published
2009
Full Text
View/download PDF

11. F.14. Autoantibodies to Myelin Oligodendrocyte Glycoprotein in Pediatric MS

Author

David A. Hafler, Ludwig Kappos, Brenda Banwell, Jens Kuhle, Katherine McLaughlin, Kevin C. O’Connor, Kai W. Wucherpfennig, Bettina Franz, Susan Wong, Tanuja Chitnis, Kevin Rostasy, Daniela Pohl, Norma P. Tavakoli, Silvia Tenembaum, and Amit Bar-Or

Subjects
030203 arthritis & rheumatology, 0303 health sciences, 03 medical and health sciences, 0302 clinical medicine, biology, Chemistry, Immunology, biology.protein, Autoantibody, Immunology and Allergy, Molecular biology, 030304 developmental biology, Myelin oligodendrocyte glycoprotein
Published
2008
Full Text
View/download PDF

13. OR.102. The CD58 Pathway is Implicated in MS Susceptibility

Author

Lisa F. Barcellos, Howard L. Weiner, Aarno Palotie, David A. Hafler, Maragaret Pericak-Vance, Stephen Sawcer, Janna Saarela, Bénédicte Dubois, David R. Booth, John D. Rioux, Jorge R. Oksenberg, Jonathan L. Haines, Lisa M. Maier, Mark J. Daly, Leena Peltonen, Alicja Waliszewska, Clare Baecher-Allan, Graeme J. Stewart, An Goris, Philip L. De Jager, and Stephen L. Hauser

Subjects
Genetics, 0303 health sciences, 03 medical and health sciences, 0302 clinical medicine, CD58, Immunology, Immunology and Allergy, Biology, 030304 developmental biology, 030215 immunology
Published
2008
Full Text
View/download PDF

14. F.33. Genetic Variants that Control the Expression of MHC Genes Do Not Affect Susceptibility to Multiple Sclerosis

Author

Roman Yelensky, Linda Ottoboni, David A. Hafler, Philip L. De Jager, Mark J. Daly, and Erica Young

Subjects
Genetics, biology, Multiple sclerosis, Immunology, Genetic variants, Major histocompatibility complex, medicine.disease, Affect (psychology), Expression (architecture), biology.protein, medicine, Immunology and Allergy, Control (linguistics), Gene
Published
2008
Full Text
View/download PDF

22. Regulation of Immunological Tolerance and Autoimmunity by the Enzyme Sialic Acid Acetylesterase (SIAE)

Author

Vasant Chellappa, David A. Hafler, Mandakolathur R. Murali, Daphne W. Bell, Stephan P. Pirnie, Cariappa Annaiah, Shiv Pillai, Kendra N. Taylor, Phillip L. De Jager, Peter Gregersen, Jesse Moya, Ira Surolia, Khaleda Haider, Bruce E. Sands, and Tim Behrens

Subjects
chemistry.chemical_classification, Enzyme, Biochemistry, Chemistry, Immunology, Sialic acid acetylesterase, medicine, Immunology and Allergy, medicine.disease_cause, Autoimmunity
Published
2010
Full Text
View/download PDF

26. Monocytes from Patients with Type 1 Diabetes Have Increased Gene Expression of Pro-inflammatory Cytokines or IL-10

Author

Peter A. Gottlieb, Wassim Elyaman, Allison Greer, David A. Hafler, Tihamer Orban, Sally C. Kent, Khadir Raddassi, Elizabeth M. Bradshaw, and Narine Mousissian

Subjects
Type 1 diabetes, Interleukin 10, business.industry, Immunology, Gene expression, medicine, Immunology and Allergy, Interleukin 19, medicine.disease, business, Proinflammatory cytokine
Published
2010
Full Text
View/download PDF

42. F.34. Changes in the CD8dimCD4- Cell Population Parallel Disease Activity in Treated Multiple Sclerosis Subjects

Author

Philip L. De Jager, Elena S. Izmailova, Pia Kivisäkk, Dulce Soler-Ferran, David A. Hafler, Howard L. Weiner, Samia J. Khoury, Carmeline O'Brien, and Xinli Hu

Subjects
education.field_of_study, business.industry, Multiple sclerosis, Immunology, Population, Cell, medicine.disease, Disease activity, medicine.anatomical_structure, Immunology and Allergy, Medicine, business, education
Published
2008
Full Text
View/download PDF

49. Characterization of Single B Cell Immunoglobulin Variable Region Genes Derived from Infiltrated Muscle Tissue of Subjects with Inflammatory Myopathies

Author

Kevin C. O’Connor, Elizabeth M. Bradshaw, Shannon L. McArdel, David A. Hafler, Ana Orihuela, and Anthony A. Amato

Subjects
Muscle tissue, Pathology, medicine.medical_specialty, medicine.anatomical_structure, Immunology, medicine, Immunology and Allergy, Immunoglobulin Variable Region, Biology, Gene, B cell
Published
2007
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results