A5039030016- Multiple Sclerosis Research Studies
- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Peripheral Neuropathies and Disorders
- Virology and Viral Diseases
- Immunodeficiency and Autoimmune Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Systemic Lupus Erythematosus Research
- Neurogenesis and neuroplasticity mechanisms
- Polyomavirus and related diseases
- Herpesvirus Infections and Treatments
- Autoimmune Neurological Disorders and Treatments
- RNA regulation and disease
- RNA Research and Splicing
- RNA Interference and Gene Delivery
- Long-Term Effects of COVID-19
- Cell death mechanisms and regulation
- Viral Infections and Immunology Research
- RNA and protein synthesis mechanisms
- Neuroscience and Neuropharmacology Research
- Bacteriophages and microbial interactions
- Receptor Mechanisms and Signaling
- Complement system in diseases
- Cell Adhesion Molecules Research
University of Colorado System
2020-2025
University of Colorado Denver
2011-2023
Neurology, Inc
1999-2023
University of Colorado Anschutz Medical Campus
2006-2023
National Multiple Sclerosis Society
2017
The Medical Center of Aurora
2015
University of Pittsburgh
1988-2014
University of Göttingen
2010
University of Colorado Health
1998-2008
Vanderbilt University Medical Center
2007
The serum of most neuromyelitis optica (NMO) patients contains autoantibodies (NMO-IgGs) directed against the aquaporin-4 (AQP4) water channel located on astrocyte foot processes in perivessel and subpial areas brain. Our objectives were to determine source central nervous system (CNS) NMO-IgGs their role disease pathogenesis.Fluorescence-activated cell sorting single-cell reverse transcriptase polymerase chain reaction used identify overrepresented plasma immunoglobulin (Ig) sequences...
Programmed cell death is an essential cellular process that occurs in epithelial turnover, neural development, and regulation of populations the immune system. Thymocytes undergo programmed response to several inductive stimuli, including exposure glucocorticoids or radiation. This program can be blocked by inhibitors RNA protein synthesis; this implies new proteins are required execute programs. To search for possible death-associated mRNAs, we directionally cloned cDNA representing mRNA...
Programmed cell death is an essential cellular process that occurs in epithelial turnover, neural development, and regulation of populations the immune system. Thymocytes undergo programmed response to several inductive stimuli, including exposure glucocorticoids or radiation. This program can be blocked by inhibitors RNA protein synthesis; this implies new proteins are required execute programs. To search for possible death-associated mRNAs, we directionally cloned cDNA representing mRNA...
Abstract Single-cell RT-PCR was used to sample CD19+ B cell repertoires in cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) or viral meningitis. Analysis amplified Ab H and L chain products served identify the rearranged germline segment J segment, determine degree homology for sequence individual cells. The repertoire meningitis CSF predominately polyclonal, whereas clonal expansion a prominent feature IgG three four MS patients. Two dominant populations one accounted ∼70%...
Abstract Objective Intrathecal IgG synthesis, persistence of bands oligoclonal IgG, and memory B‐cell clonal expansion are well‐characterized features the humoral response in multiple sclerosis (MS). Nevertheless, target antigen this remains enigmatic. Methods We produced 53 different human IgG1 monoclonal recombinant antibodies (rAbs) by coexpressing paired heavy‐ light‐chain variable region sequences 51 plasma cell clones 2 B‐lymphocyte from MS cerebrospinal fluid tissue culture cells....
<b>Objective:</b> Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus that becomes latent in B-lymphocytes and has been implicated the pathogenesis of multiple sclerosis (MS). We searched for active EBV infection MS brain CSF. <b>Methods:</b> Nested non-nested real-time PCR were used to detect cell-specific EBV-specific transcripts 15 fresh-frozen 5 formalin-fixed paraffin-embedded plaques single CSF plasma cells. Intrathecal anti-EBV antibody synthesis was measured by ELISA....
Antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) are present in some neuromyelitis optica patients who lack antibodies aquaporin-4 (AQP4-IgG). The effects of MOG-IgG the central nervous system have not been investigated vivo. We microinjected MOG-IgG, obtained from with optica, into mouse brains and compared results AQP4-IgG. caused changes altered expression axonal proteins that essential for action potential firing, but did produce inflammation, loss, neuronal or astrocyte...
An autoantibody target on brain microvascular endothelial cells in patients with neuromyelitis optica may be exploited to manipulate blood-brain barrier permeability.
Neuromyelitis optica (NMO) is an autoimmune CNS disorder mediated by pathogenic aquaporin-4 (AQP4) water channel autoantibodies (AQP4-IgG). Although AQP4-IgG-driven complement-dependent cytotoxicity (CDC) critical for the formation of NMO lesions, molecular mechanisms governing optimal classical pathway activation are unknown. We investigated determinants driving CDC in using recombinant AQP4-specific (AQP4 rAbs) derived from affected patients. identified a group AQP4 rAbs targeting distinct...
Abstract Multiple sclerosis (MS) cerebrospinal fluid and brain contain increased IgG oligoclonal bands. Whether this polyclonal is directed against a disease‐relevant antigen remains unknown. To distinguish between random activation versus targeted B‐cell response, we analyzed the heavy chain variable region (V H ) repertoire expressed in different lesions of an acute MS brain. obtain representative sample V repertoire, constructed directional complementary DNA libraries from...
Double negative (DN) (CD19 + CD20 low CD27 - IgD ) B cells are expanded in patients with autoimmune and infectious diseases; however their role the humoral immune response remains unclear. Using systematic flow cytometric analyses of peripheral blood cell subsets, we observed an inflated DN population variety active inflammatory conditions: myasthenia gravis, Guillain-Barré syndrome, neuromyelitis optica spectrum disorder, meningitis/encephalitis, rheumatic disorders. Furthermore, were able...
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of unknown cause that afflicts the central nervous system. MS typified by highly clonally restricted antigen-driven antibody response confined largely to The major antigenic targets this and role in pathogenesis remain unclear. To help resolve these issues, we cloned IgG repertoire directly from active plaque periplaque regions brain B cells recovered cerebrospinal fluid patient with subacute disease. We found...
Multiple sclerosis (MS) is a chronic demyelinating disorder of unknown etiology, possibly caused by virus or virus-triggered immunopathology. The might reactivate after years latency and lyse oligodendrocytes, as in progressive multifocal leukoencephalopathy, initiate immunopathological demyelination, animals infected with Theiler’s murine encephalomyelitis coronaviruses. argument for viral cause MS supported epidemiological analyses studies identical twins, indicating that disease acquired....
Intrathecal immunoglobulin G (IgG) synthesis, cerebrospinal fluid (CSF) oligoclonal IgG bands and lesional deposition are seminal features of multiple sclerosis (MS) disease pathology. Both the specific targets pathogenic effects MS antibodies remain poorly characterized. We produced IgG1 monoclonal recombinant (rAbs) from clonally-expanded plasmablasts recovered patient CSF. Among these were a subset myelin-specific rAbs. examined their immunoreactivity to mouse organotypic cerebellar...
Neuromyelitis optica (NMO) is a severe demyelinating disorder of the central nervous system (CNS) associated with presence an autoimmune antibody response (AQP4-IgG) against water channel aquaporin-4 (AQP4). It remains unclear whether pathologic AQP4-IgG in CNS produced entirely by peripheral plasma cells or generated part infiltrating B cells. To determine overlap idiotypes between and periphery, we compared immunoglobulin G (IgG) transcriptome cerebrospinal fluid (CSF) plasmablasts CSF...
Abstract Objectives Neuromyelitis optica spectrum disorder (NMOSD) is a severe inflammatory of the central nervous system (CNS) targeted against aquaporin‐4 (AQP4). The origin and trafficking AQP4‐specific B cells in NMOSD remains unknown. Methods Peripheral ( n = 7) splenic 1) recovered from seven patients were sorted into plasmablasts, naïve, memory, CD27‐IgD‐ double negative (DN) cells, variable heavy chain (VH) transcriptome sequences generated by deep sequencing. blood (PB) VH...
<b><i>Objective:</i></b> To better understand B-cell activation in MS by analyzing the immunoglobulin (Ig) G heavy chain variable region (VH) repertoire found brains and comparing it with brain VH sequences individuals subacute sclerosing panencephalitis (SSPE)—a chronic encephalitis produced measles virus (MV)—and characterized an antigen-driven oligoclonal IgG response to MV antigens. <b><i>Background:</i></b> The specificity of CSF plaques, their relevance pathogenesis is unknown....
Abstract Increased amounts of intrathecally synthesized IgG and oligoclonal bands have long been recognized as a hallmark multiple sclerosis (MS). B cells plasma are components the inflammatory infiltrates in both active chronic MS lesions, increased numbers these present cerebrospinal fluid (CSF). Single-cell RT-PCR was used to analyze CD19+ cell CD138+ populations CSF two patients with clinically definite one patient whose obtained after isolated syndrome, but before second episode....