LIVIVO - Search results -

Search results

Result 1 - 10 of total 64

Search options

Article ; Online: The repertoire of CSF antiviral antibodies in patients with neuroinflammatory diseases.

Enose-Akahata, Yoshimi / Wang, Limin / Almsned, Fahad / Johnson, Kory R / Mina, Yair / Ohayon, Joan / Wang, Xin Wei / Jacobson, Steven

Science advances

2023 Volume 9, Issue 1, Page(s) eabq6978

Abstract: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Although various viruses have been proposed to contribute to MS pathology, the etiology of MS remains unknown. Since intrathecal antibody ... ...

Abstract	Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Although various viruses have been proposed to contribute to MS pathology, the etiology of MS remains unknown. Since intrathecal antibody synthesis is well documented in chronic viral infection and neuroinflammatory diseases, we hypothesized whether the patterns of antigen-specific antibody responses associated with various viral exposures may define patients with CNS chronic immune dysregulation. The pan-viral antibody profiling in cerebrospinal fluid (CSF) and serum of patients with MS showed significant differences from those in healthy volunteers and a pattern of antibody responses against multiple viruses, including the previously identified Epstein-Barr virus. These findings demonstrate that virus-specific antibody signatures might be able to reflect disease-associated inflammatory milieu in CSF of subjects with neuroinflammatory diseases.
MeSH term(s)	Humans ; Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; Neuroinflammatory Diseases ; Antiviral Agents ; Multiple Sclerosis
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2023-01-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.abq6978
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article: Unstable EBV latency drives inflammation in multiple sclerosis patient derived spontaneous B cells.

Soldan, Samantha / Su, Chenhe / Monaco, Maria Chiara / Brown, Natalie / Clauze, Annaliese / Andrada, Frances / Feder, Andries / Planet, Paul / Kossenkov, Andrew / Schäffer, Daniel / Ohayon, Joan / Auslander, Noam / Jacobson, Steve / Lieberman, Paul

Research square

2023

Abstract: Epidemiological studies have demonstrated that Epstein-Barr virus (EBV) is a known etiologic risk factor, and perhaps prerequisite, for the development of MS. EBV establishes life-long latent infection in a subpopulation of memory B cells. Although the ... ...

Abstract	Epidemiological studies have demonstrated that Epstein-Barr virus (EBV) is a known etiologic risk factor, and perhaps prerequisite, for the development of MS. EBV establishes life-long latent infection in a subpopulation of memory B cells. Although the role of memory B cells in the pathobiology of MS is well established, studies characterizing EBV-associated mechanisms of B cell inflammation and disease pathogenesis in EBV (+) B cells from MS patients are limited. Accordingly, we analyzed spontaneous lymphoblastoid cell lines (SLCLs) from multiple sclerosis patients and healthy controls to study host-virus interactions in B cells, in the context of an individual's endogenous EBV. We identify differences in EBV gene expression and regulation of both viral and cellular genes in SLCLs. Our data suggest that EBV latency is dysregulated in MS SLCLs with increased lytic gene expression observed in MS patient B cells, especially those generated from samples obtained during "active" disease. Moreover, we show increased inflammatory gene expression and cytokine production in MS patient SLCLs and demonstrate that tenofovir alafenamide, an antiviral that targets EBV replication, decreases EBV viral loads, EBV lytic gene expression, and EBV-mediated inflammation in both SLCLs and in a mixed lymphocyte assay. Collectively, these data suggest that dysregulation of EBV latency in MS drives a pro-inflammatory, pathogenic phenotype in memory B cells and that this response can be attenuated by suppressing EBV lytic activation. This study provides further support for the development of antiviral agents that target EBV-infection for use in MS.
Language	English
Publishing date	2023-02-01
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-2398872/v1
Database	MEDical Literature Analysis and Retrieval System OnLINE

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾

Article ; Online: EBNA1 Inhibitors Block Proliferation of Spontaneous Lymphoblastoid Cell Lines From Patients With Multiple Sclerosis and Healthy Controls.

Monaco, Maria Chiara G / Soldan, Samantha S / Su, Chenhe / Clauze, Annaliese / Cooper, John F / Patel, Rishi J / Lu, Fang / Hughes, Randall J / Messick, Troy E / Andrada, Frances C / Ohayon, Joan / Lieberman, Paul M / Jacobson, Steven

Neurology(R) neuroimmunology & neuroinflammation

2023 Volume 10, Issue 5

Abstract: Background and objectives: Epstein-Barr virus (EBV) is a ubiquitous herpesvirus that establishes lifelong latency in memory B cells and has been identified as a major risk factor of multiple sclerosis (MS). B cell depletion therapies have disease- ... ...

Abstract	Background and objectives: Epstein-Barr virus (EBV) is a ubiquitous herpesvirus that establishes lifelong latency in memory B cells and has been identified as a major risk factor of multiple sclerosis (MS). B cell depletion therapies have disease-modifying benefit in MS. However, it is unclear whether this benefit is partly attributable to the elimination of EBV Methods: In this study, we describe the establishment of spontaneous lymphoblastoid cell lines (SLCLs) generated ex vivo with the endogenous EBV of patients with MS and controls and treated with either an Epstein-Barr virus nuclear antigen 1 (EBNA1) inhibitor (VK-1727) or cladribine, a nucleoside analog that eliminates B cells. Results: We showed that a small molecule inhibitor of EBNA1, a critical regulator of the EBV life cycle, blocks the proliferation and metabolic activity of these SLCLs. In contrast to cladribine, a highly cytotoxic B cell depleting therapy currently used in MS, the EBNA1 inhibitor VK-1727 was cytostatic rather than cytotoxic and selective for EBV Discussion: This study shows that patient-derived SLCLs provide a useful tool for interrogating the role of EBV
MeSH term(s)	Humans ; Cell Line ; Cell Proliferation ; Cladribine/pharmacology ; Epstein-Barr Virus Infections/complications ; Epstein-Barr Virus Infections/drug therapy ; Epstein-Barr Virus Infections/genetics ; Epstein-Barr Virus Nuclear Antigens ; Herpesvirus 4, Human ; Multiple Sclerosis ; Case-Control Studies
Chemical Substances	Cladribine (47M74X9YT5) ; Epstein-Barr Virus Nuclear Antigens
Language	English
Publishing date	2023-08-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2767740-0
ISSN	2332-7812 ; 2332-7812
ISSN (online)	2332-7812
ISSN	2332-7812
DOI	10.1212/NXI.0000000000200149
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Effect of Teriflunomide on Cells From Patients With Human T-cell Lymphotropic Virus Type 1-Associated Neurologic Disease.

Enose-Akahata, Yoshimi / Ngouth, Nyater / Ohayon, Joan / Mandel, Matt / Chavin, Jeffrey / Turner, Timothy J / Jacobson, Steven

Neurology(R) neuroimmunology & neuroinflammation

2021 Volume 8, Issue 3

Abstract: Objective: To test the hypothesis that teriflunomide can reduce ex vivo spontaneous proliferation of peripheral blood mononuclear cells (PBMCs) from patients with human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic ... ...

Abstract	Objective: To test the hypothesis that teriflunomide can reduce ex vivo spontaneous proliferation of peripheral blood mononuclear cells (PBMCs) from patients with human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Methods: PBMCs from patients with HAM/TSP were cultured in the presence and absence of teriflunomide and assessed for cell viability, lymphocyte proliferation, activation markers, HTLV-1 Results: In culture, teriflunomide did not affect cell viability. A concentration-dependent reduction in spontaneous proliferation of PBMCs was observed with 25 μM (38.3% inhibition), 50 μM (65.8% inhibition), and 100 μM (90.7% inhibition) teriflunomide. The inhibitory effects of teriflunomide were detected in both CD8 Conclusions: These results suggest that teriflunomide inhibits abnormal T-cell proliferation associated with HTLV-1 infection and may have potential as a therapeutic option in patients with HAM/TSP.
MeSH term(s)	Adult ; Aged ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Crotonates/pharmacology ; Female ; Gene Products, tax/metabolism ; HTLV-I Infections/complications ; Human T-lymphotropic virus 1/genetics ; Humans ; Hydroxybutyrates/pharmacology ; Leukocytes, Mononuclear/drug effects ; Male ; Middle Aged ; Nitriles/pharmacology ; Paraparesis, Tropical Spastic/drug therapy ; Primary Cell Culture ; RNA, Messenger/metabolism ; T-Lymphocyte Subsets/drug effects ; Toluidines/pharmacology
Chemical Substances	Crotonates ; Gene Products, tax ; Hydroxybutyrates ; Nitriles ; RNA, Messenger ; Toluidines ; teriflunomide (1C058IKG3B)
Language	English
Publishing date	2021-04-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2767740-0
ISSN	2332-7812 ; 2332-7812
ISSN (online)	2332-7812
ISSN	2332-7812
DOI	10.1212/NXI.0000000000000986
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Immunopathogenic CSF TCR repertoire signatures in virus-associated neurologic disease.

Nozuma, Satoshi / Enose-Akahata, Yoshimi / Johnson, Kory R / Monaco, Maria Chiara / Ngouth, Nyater / Elkahloun, Abdel / Ohayon, Joan / Zhu, Jun / Jacobson, Steven

JCI insight

2021 Volume 6, Issue 4

Abstract: In this study, we examined and characterized disease-specific TCR signatures in cerebrospinal fluid (CSF) of patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). TCR β libraries using unique molecular identifier-based ... ...

Abstract	In this study, we examined and characterized disease-specific TCR signatures in cerebrospinal fluid (CSF) of patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). TCR β libraries using unique molecular identifier-based methodologies were sequenced in paired peripheral blood mononuclear cells (PBMCs) and CSF cells from HAM/TSP patients and normal healthy donors (NDs). The sequence analysis demonstrated that TCR β repertoires in CSF of HAM/TSP patients were highly expanded and contained both TCR clonotypes shared with PBMCs and uniquely enriched within the CSF. In addition, we analyzed TCR β repertoires of highly expanded and potentially immunopathologic HTLV-1 Tax11-19-specific CD8+ T cells from PBMCs of HLA-A*0201+ HAM/TSP and identified a conserved motif (PGLAG) in the CDR3 region. Importantly, TCR β clonotypes of expanded clones in HTLV-1 Tax11-19-specific CD8+ T cells were also expanded and enriched in the CSF of the same patient. These results suggest that exploring TCR repertoires of CSF and antigen-specific T cells may provide a TCR repertoire signature in virus-associated neurologic disorders.
MeSH term(s)	CD8-Positive T-Lymphocytes ; Clone Cells ; HTLV-I Infections ; Human T-lymphotropic virus 1 ; Humans ; Leukocytes, Mononuclear ; Nervous System Diseases/immunology ; Nervous System Diseases/virology ; Paraparesis, Tropical Spastic/blood ; Paraparesis, Tropical Spastic/cerebrospinal fluid ; Paraparesis, Tropical Spastic/immunology ; Receptors, Antigen, T-Cell/immunology ; Receptors, Antigen, T-Cell, alpha-beta/blood ; Receptors, Antigen, T-Cell, alpha-beta/immunology
Chemical Substances	Receptors, Antigen, T-Cell ; Receptors, Antigen, T-Cell, alpha-beta
Language	English
Publishing date	2021-02-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.144869
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Viral Immune signatures from cerebrospinal fluid extracellular vesicles and particles in HAM and other chronic neurological diseases.

Pleet, Michelle L / Welsh, Joshua A / Stack, Emily H / Cook, Sean / Johnson, Dove-Anna / Killingsworth, Bryce / Traynor, Tim / Clauze, Annaliese / Hughes, Randall / Monaco, Maria Chiara / Ngouth, Nyater / Ohayon, Joan / Enose-Akahata, Yoshimi / Nath, Avindra / Cortese, Irene / Reich, Daniel S / Jones, Jennifer C / Jacobson, Steven

Frontiers in immunology

2023 Volume 14, Page(s) 1235791

Abstract: Background and objectives: Extracellular vesicles and particles (EVPs) are released from virtually all cell types, and may package many inflammatory factors and, in the case of infection, viral components. As such, EVPs can play not only a direct role ... ...

Abstract	Background and objectives: Extracellular vesicles and particles (EVPs) are released from virtually all cell types, and may package many inflammatory factors and, in the case of infection, viral components. As such, EVPs can play not only a direct role in the development and progression of disease but can also be used as biomarkers. Here, we characterized immune signatures of EVPs from the cerebrospinal fluid (CSF) of individuals with HTLV-1-associated myelopathy (HAM), other chronic neurologic diseases, and healthy volunteers (HVs) to determine potential indicators of viral involvement and mechanisms of disease. Methods: We analyzed the EVPs from the CSF of HVs, individuals with HAM, HTLV-1-infected asymptomatic carriers (ACs), and from patients with a variety of chronic neurologic diseases of both known viral and non-viral etiologies to investigate the surface repertoires of CSF EVPs during disease. Results: Significant increases in CD8+ and CD2+ EVPs were found in HAM patient CSF samples compared to other clinical groups ( Discussion: These data suggest that CD8+ and CD2+ CSF EVPs may be important as: 1) potential biomarkers and indicators of disease pathways for viral-mediated neurological diseases, particularly HAM, and 2) as possible meditators of the disease process in infected individuals.
MeSH term(s)	Humans ; Paraparesis, Tropical Spastic ; Central Nervous System ; Extracellular Vesicles ; Nervous System Diseases ; CD40 Antigens ; Chronic Disease
Chemical Substances	CD40 Antigens
Language	English
Publishing date	2023-08-09
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Intramural
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1235791
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Central Vein Sign Profile of Newly Developing Lesions in Multiple Sclerosis: A 3-Year Longitudinal Study.

Al-Louzi, Omar / Letchuman, Vijay / Manukyan, Sargis / Beck, Erin S / Roy, Snehashis / Ohayon, Joan / Pham, Dzung L / Cortese, Irene / Sati, Pascal / Reich, Daniel S

Neurology(R) neuroimmunology & neuroinflammation

2022 Volume 9, Issue 2

Abstract: Background and objectives: The central vein sign (CVS), a central linear hypointensity within lesions on T2*-weighted imaging, has been established as a sensitive and specific biomarker for the diagnosis of multiple sclerosis (MS). However, the CVS has ... ...

Abstract	Background and objectives: The central vein sign (CVS), a central linear hypointensity within lesions on T2-weighted imaging, has been established as a sensitive and specific biomarker for the diagnosis of multiple sclerosis (MS). However, the CVS has not yet been comprehensively studied in newly developing MS lesions. We aimed to identify the CVS profiles of new white matter lesions in patients with MS followed over time and investigate demographic and clinical risk factors associated with new CVS+ or CVS- lesion development. Methods:* In this retrospective longitudinal cohort study, adults from the NIH MS Natural History Study were considered for inclusion. Participants with new T2 or enhancing lesions were identified through review of the radiology report and/or longitudinal subtraction imaging. Each new lesion was evaluated for the CVS. Clinical characteristics were identified through chart review. Results: A total of 153 adults (95 relapsing-remitting MS, 27 secondary progressive MS, 16 primary progressive MS, 5 clinically isolated syndrome, and 10 healthy; 67% female) were included. Of this cohort, 96 had at least 1 new T2 or contrast-enhancing lesion during median 3.1 years (Q1-Q3: 0.7-6.3) of follow-up; lesions eligible for CVS evaluation were found in 62 (65%). Of 233 new CVS-eligible lesions, 159 (68%) were CVS+, with 30 (48%) individuals having only CVS+, 12 (19%) only CVS-, and 20 (32%) both CVS+ and CVS- lesions. In gadolinium-enhancing (Gd+) lesions, the CVS+ percentage increased from 102/152 (67%) at the first time point where the lesion was observed, to 92/114 (82%) after a median follow-up of 2.8 years. Younger age (OR = 0.5 per 10-year increase, 95% CI = 0.3-0.8) and higher CVS+ percentage at baseline (OR = 1.4 per 10% increase, 95% CI = 1.1-1.9) were associated with increased likelihood of new CVS+ lesion development. Discussion: In a cohort of adults with MS followed over a median duration of 3 years, most newly developing T2 or enhancing lesions were CVS+ (68%), and nearly half (48%) developed new CVS+ lesions only. Importantly, the effects of edema and T2 signal changes can obscure small veins in Gd+ lesions; therefore, caution and follow-up is necessary when determining their CVS status. Trial registration information: Clinical trial registration number NCT00001248. Classification of evidence: This study provides Class III evidence that younger age and higher CVS+ percentage at baseline are associated with new CVS+ lesion development.
MeSH term(s)	Adult ; Cerebral Veins/diagnostic imaging ; Cerebral Veins/pathology ; Disease Progression ; Female ; Humans ; Longitudinal Studies ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Multiple Sclerosis/diagnostic imaging ; Multiple Sclerosis/pathology ; Retrospective Studies ; White Matter/blood supply ; White Matter/diagnostic imaging ; White Matter/pathology
Language	English
Publishing date	2022-01-13
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2767740-0
ISSN	2332-7812 ; 2332-7812
ISSN (online)	2332-7812
ISSN	2332-7812
DOI	10.1212/NXI.0000000000001120
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Cervical and thoracic cord atrophy in multiple sclerosis phenotypes: Quantification and correlation with clinical disability.

Mina, Yair / Azodi, Shila / Dubuche, Tsemacha / Andrada, Frances / Osuorah, Ikesinachi / Ohayon, Joan / Cortese, Irene / Wu, Tianxia / Johnson, Kory R / Reich, Daniel S / Nair, Govind / Jacobson, Steven

NeuroImage. Clinical

2021 Volume 30, Page(s) 102680

Abstract: Objective: We sought to characterize spinal cord atrophy along the entire spinal cord in the major multiple sclerosis (MS) phenotypes, and evaluate its correlation with clinical disability.: Methods: Axial T: Results: The cross-sectional study ... ...

Abstract	Objective: We sought to characterize spinal cord atrophy along the entire spinal cord in the major multiple sclerosis (MS) phenotypes, and evaluate its correlation with clinical disability. Methods: Axial T Results: The cross-sectional study consisted of 149 adults diagnosed with relapsing-remitting MS (RRMS), 49 with secondary-progressive MS (SPMS), 58 with primary-progressive MS (PPMS) and 48 controls. The longitudinal study included 78 RRMS cases. Compared to controls, all MS groups had smaller average regions except RRMS in T4-9 region. In all MS groups, SCCSA from all regions, particularly the cervical cord, correlated with most clinical measures. In the RRMS cohort, 22% of cases had at least one atrophic region, whereas in progressive MS the rate was almost 70%. Longitudinal analysis showed correlation between clinical disability and cervical cord thinning. Conclusions: Spinal cord atrophy was prevalent across MS phenotypes, with regional measures from the RRMS cohort and the progressive cohort, including SPMS and PPMS, being correlated with disability. Longitudinal changes in the spinal cord were documented in RRMS cases, making it a potential marker for disease progression. While cervical SCCSA correlated with most disability and progression measures, inclusion of thoracic measurements improved this correlation and allowed for better subgrouping of spinal cord phenotypes. Cord atrophy is an important and easily obtainable imaging marker of clinical and sub-clinical progression in all MS phenotypes, and such measures can play a key role in patient selection for clinical trials.
MeSH term(s)	Adult ; Atrophy/pathology ; Cervical Cord/diagnostic imaging ; Cervical Cord/pathology ; Cross-Sectional Studies ; Disability Evaluation ; Disease Progression ; Humans ; Longitudinal Studies ; Magnetic Resonance Imaging ; Multiple Sclerosis/diagnostic imaging ; Multiple Sclerosis/pathology ; Multiple Sclerosis, Relapsing-Remitting/diagnostic imaging ; Multiple Sclerosis, Relapsing-Remitting/pathology ; Phenotype ; Spinal Cord/pathology
Language	English
Publishing date	2021-04-28
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	2701571-3
ISSN	2213-1582 ; 2213-1582
ISSN (online)	2213-1582
ISSN	2213-1582
DOI	10.1016/j.nicl.2021.102680
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Comprehensive Analysis of TCR-β Repertoire in Patients with Neurological Immune-mediated Disorders.

Alves Sousa, Alessandra de Paula / Johnson, Kory R / Ohayon, Joan / Zhu, Jun / Muraro, Paolo A / Jacobson, Steven

Scientific reports

2019 Volume 9, Issue 1, Page(s) 344

Abstract: In this study we characterized the TCR repertoire profiles in patients with chronic progressive inflammatory neurological disorders including HAM/TSP, associated with human T-cell lymphotropic virus type I (HTLV-I) infection, and multiple sclerosis (MS), ...

Abstract	In this study we characterized the TCR repertoire profiles in patients with chronic progressive inflammatory neurological disorders including HAM/TSP, associated with human T-cell lymphotropic virus type I (HTLV-I) infection, and multiple sclerosis (MS), an inflammatory, demyelinating disease of the CNS of unknown etiology. We hypothesized that a T-cell receptor (TCR) clonal repertoire 'signature' could distinguish HAM/TSP patients from healthy controls, as well as from patients with a more heterogeneous CNS-reactive inflammatory disease such as MS. In this study, we applied an unbiased molecular technique - unique molecular identifier (UMI) library-based strategy to investigate with high accuracy the TCR clonal repertoire by high throughput sequencing (HTS) technology. cDNA-TCR β-chain libraries were sequenced from 2 million peripheral mononuclear cells (PBMCs) in 14 HAM/TSP patients, 34 MS patients and 20 healthy controls (HC). While HAM/TSP patients showed a higher clonal T-cell expansion compared to MS and HC, increase of the TCR clonal expansion was inversely correlated with the diversity of TCR repertoire in all subjects. In addition, longitudinal analysis of TCR repertoires from HAM/TSP patients demonstrated a correlation of the TCR clonal expansion with HTLV-I proviral load. Surprisingly, MS patients showed a higher diversity of TCR repertoires than other groups. Despite higher TCR clonal expansions in HAM/TSP patients, no disease-specific TCRs were shared among patients. Only non-shared or "private" TCR repertoires was observed. While no clones that shared the same CDR3 amino acid sequences were seen in either HC or MS patients, there was a cluster of related CDR3 amino acid sequences observed for 18 out of 34 MS patients when evaluated by phylogenetic tree analysis. This suggests that a TCR-repertoire signature may be identified in a subset of patients with MS.
MeSH term(s)	Adult ; Aged ; Female ; Genetic Variation ; HTLV-I Infections/pathology ; Humans ; Leukocytes, Mononuclear/pathology ; Longitudinal Studies ; Male ; Middle Aged ; Multiple Sclerosis/pathology ; Receptors, Antigen, T-Cell, alpha-beta/genetics ; Sequence Analysis, DNA ; Time Factors ; Viral Load ; Young Adult
Chemical Substances	Receptors, Antigen, T-Cell, alpha-beta
Language	English
Publishing date	2019-01-23
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-018-36274-7
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Clinical trial of raltegravir, an integrase inhibitor, in HAM/TSP.

Enose-Akahata, Yoshimi / Billioux, Bridgette Jeanne / Azodi, Shila / Dwyer, Jennifer / Vellucci, Ashley / Ngouth, Nyater / Nozuma, Satoshi / Massoud, Raya / Cortese, Irene / Ohayon, Joan / Jacobson, Steven

Annals of clinical and translational neurology

2021 Volume 8, Issue 10, Page(s) 1970–1985

Abstract: Objective: Human T-cell lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic, progressive myelopathy. A high proviral load (PVL) is one of the main risk factors for HAM/TSP. Recently, it was shown that ... ...

Abstract	Objective: Human T-cell lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic, progressive myelopathy. A high proviral load (PVL) is one of the main risk factors for HAM/TSP. Recently, it was shown that raltegravir could inhibit cell-free and cell-to-cell transmission of HTLV-1 in vitro. Given the substantial clinical experience in human immunodeficiency virus infection and its excellent safety profile, this agent may be an attractive therapeutic option for HAM/TSP patients. Methods: Sixteen subjects with HAM/TSP received raltegravir 400 mg orally twice daily in an initial 6-month treatment phase, followed by a 9-month post-treatment phase. HTLV-1 PVLs were assessed using droplet digital PCR from the PBMCs every 3 months, and from the CSF at baseline, month 6, and month 15. We also evaluated the ability of raltegravir to regulate abnormal immune responses in HAM/TSP patients. Results: While a downward trend was observed in PBMC and/or CSF PVLs of some patients, raltegravir overall did not have any impact on the PVL in this HAM/TSP patient cohort. Clinically, all patients' neurological scores and objective measurements remained relatively stable, with some expected variability. Immunologic studies showed alterations in the immune profiles of a subset of patients including decreased CD4 Interpretation: Raltegravir was generally well tolerated in this HAM/TSP patient cohort. A subset of patients exhibited a mild decrease in PVL as well as variations in their immune profiles after taking raltegravir. These findings suggest that raltegravir may be a therapeutic option in select HAM/TSP patients. Clinical trial registration number: NCT01867320.
MeSH term(s)	Adult ; Aged ; Female ; Humans ; Integrase Inhibitors/administration & dosage ; Integrase Inhibitors/pharmacology ; Male ; Middle Aged ; Paraparesis, Tropical Spastic/drug therapy ; Pilot Projects ; Raltegravir Potassium/administration & dosage ; Raltegravir Potassium/pharmacology ; Treatment Outcome
Chemical Substances	Integrase Inhibitors ; Raltegravir Potassium (43Y000U234)
Language	English
Publishing date	2021-09-25
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	2740696-9
ISSN	2328-9503 ; 2328-9503
ISSN (online)	2328-9503
ISSN	2328-9503
DOI	10.1002/acn3.51437
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

To top

More links

Kategorien

Order via subito

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito