Abstract:
:In multiple sclerosis (MS), lymphocyte--in particular B cell--transit between the central nervous system (CNS) and periphery may contribute to the maintenance of active disease. Clonally related B cells exist in the cerebrospinal fluid (CSF) and peripheral blood (PB) of MS patients; however, it remains unclear which subpopulations of the highly diverse peripheral B cell compartment share antigen specificity with intrathecal B cell repertoires and whether their antigen stimulation occurs on both sides of the blood-brain barrier. To address these questions, we combined flow cytometric sorting of PB B cell subsets with deep immune repertoire sequencing of CSF and PB B cells. Immunoglobulin (IgM and IgG) heavy chain variable (VH) region repertoires of five PB B cell subsets from MS patients were compared with their CSF Ig-VH transcriptomes. In six of eight patients, we identified peripheral CD27(+)IgD(-) memory B cells, CD27(hi)CD38(hi) plasma cells/plasmablasts, or CD27(-)IgD(-) B cells that had an immune connection to the CNS compartment. Pinpointing Ig class-switched B cells as key component of the immune axis thought to contribute to ongoing MS disease activity strengthens the rationale of current B cell-targeting therapeutic strategies and may lead to more targeted approaches.
journal_name
Sci Transl Medjournal_title
Science translational medicineauthors
Palanichamy A,Apeltsin L,Kuo TC,Sirota M,Wang S,Pitts SJ,Sundar PD,Telman D,Zhao LZ,Derstine M,Abounasr A,Hauser SL,von Büdingen HCdoi
10.1126/scitranslmed.3008930subject
Has Abstractpub_date
2014-08-06 00:00:00pages
248ra106issue
248eissn
1946-6234issn
1946-6242journal_volume
6pub_type
杂志文章abstract::Heparin-based anticoagulant drugs have been widely used for the prevention of blood clotting during surgical procedures and for the treatment of thromboembolic events. However, bleeding risks associated with these anticoagulants demand continuous monitoring and neutralization with suitable antidotes. Protamine, the on...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3009427
更新日期:2014-10-29 00:00:00
abstract::Functional magnetic resonance imaging offers an unprecedented opportunity to evaluate and compare drug effects on human brain activity and to provide systems-level predictions for how new drugs for chronic pain will affect the brain, thus accelerating drug discovery and repurposing (Duff et al., this issue). ...
journal_title:Science translational medicine
pub_type: 评论,杂志文章
doi:10.1126/scitranslmed.3010342
更新日期:2015-02-11 00:00:00
abstract::The inability to produce perfusable microvasculature networks capable of supporting tissue survival and of withstanding physiological pressures without leakage is a fundamental problem facing the field of tissue engineering. Microvasculature is critically important for production of bioengineered lung (BEL), which req...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aao3926
更新日期:2018-08-01 00:00:00
abstract::A congenital or iatrogenic tissue defect often requires closure by open surgery or metallic components that can erode tissue. Biodegradable, hydrophobic light-activated adhesives represent an attractive alternative to sutures, but lack a specifically designed minimally invasive delivery tool, which limits their clinic...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aaa2406
更新日期:2015-09-23 00:00:00
abstract::As part of the global effort toward malaria eradication, phenotypic whole-cell screening revealed the 2-aminopyridine class of small molecules as a good starting point to develop new antimalarial drugs. Stemming from this series, we found that the derivative, MMV390048, lacked cross-resistance with current drugs used ...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aad9735
更新日期:2017-04-26 00:00:00
abstract::Understanding the biological properties of plasma cell-free DNA may expand its applications in oncology (Mouliere et al, this issue). ...
journal_title:Science translational medicine
pub_type: 评论,杂志文章,评审
doi:10.1126/scitranslmed.aav3873
更新日期:2018-11-07 00:00:00
abstract::Atherosclerosis is the cause of morbiditiy for 70% of patients with type 2 diabetes. In both of these diseases, a protein complex known as the inflammasome is stimulated to activate interleukin-1β (IL-1β) and IL-18, which are pathogenic inflammatory cytokines. Triggers for the inflammasome are obesity-related factors,...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3001902
更新日期:2011-05-04 00:00:00
abstract::Glucagon-like peptide-1 receptor (GLP1R) agonists and dipeptidyl peptidase 4 inhibitors are widely prescribed diabetes drugs due to their ability to stimulate insulin secretion from remaining β cells and to reduce caloric intake. Unfortunately, they fail to increase human β cell proliferation. Small-molecule inhibitor...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aaw9996
更新日期:2020-02-12 00:00:00
abstract::Cancer research integrated a physical sciences perspective through team science, which fostered communication, trust, joint publication, and open access to data. ...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3005804
更新日期:2013-05-01 00:00:00
abstract::A rare neurodevelopmental disorder in the Old Order Mennonite population called PMSE (polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome; also called Pretzel syndrome) is characterized by infantile-onset epilepsy, neurocognitive delay, craniofacial dysmorphism, and histopathological evidence of heteroto...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3005271
更新日期:2013-04-24 00:00:00
abstract::Osteoarthritis (OA) is a common degenerative condition that afflicts more than 70% of the population between 55 and 77 years of age. Although its prevalence is rising globally with aging of the population, current therapy is limited to symptomatic relief and, in severe cases, joint replacement surgery. We report that ...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3005409
更新日期:2013-03-13 00:00:00
abstract::Prolonged life expectancy in the 20th century has been one of humankind's greatest triumphs. However, the substantial increase in the human life span has ushered in a new concern: healthy aging. Because infectious diseases prominently contribute to morbidity in the particularly vulnerable elderly population, strategie...
journal_title:Science translational medicine
pub_type: 杂志文章,评审
doi:10.1126/scitranslmed.3005624
更新日期:2013-05-15 00:00:00
abstract::Cooperative oncogenic effects resulting from the loss of PTEN and overexpression of MYC overcome the deleterious effects of endoplasmic reticulum stress not only to promote the growth of aggressive prostate cancer but also to expose a new therapy target for this disease (Nguyen et al, this issue). ...
journal_title:Science translational medicine
pub_type: 杂志文章,评审
doi:10.1126/scitranslmed.aat3975
更新日期:2018-05-02 00:00:00
abstract::Treatment of life-threatening Epstein-Barr virus (EBV)-associated tumors remains a great challenge, especially for patients with relapsed or refractory disease. Here, we found that exosomes derived from phosphoantigen-expanded Vδ2-T cells (Vδ2-T-Exos) contained death-inducing ligands (FasL and TRAIL), an activating re...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aaz3426
更新日期:2020-09-30 00:00:00
abstract::Axonal dystrophy, indicative of perturbed axonal transport, occurs early during Alzheimer's disease (AD) pathogenesis. Little is known about the mechanisms underlying this initial sign of the pathology. This study proves that Golgi-localized γ-ear-containing ARF binding protein 3 (GGA3) loss of function, due to Gga3 g...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aba1871
更新日期:2020-11-18 00:00:00
abstract::EphB receptors regulate the proliferation and positioning of intestinal stem and progenitor cells. In addition, they can act as tumor promoters for adenoma development but suppress progression to invasive carcinoma. We used imatinib to abrogate Abl kinase activity in Apc(Min/+) mice and in mice with LGR5(+) stem cells...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3010567
更新日期:2015-04-01 00:00:00
abstract::Numerous studies have implicated microRNAs (miRNAs) in cancer initiation and progression. In contrast, only recently has attention been focused on the pathway that generates these regulatory molecules. The identification of neoplasia-associated germline mutations in DICER1 has focused translational research on compone...
journal_title:Science translational medicine
pub_type: 杂志文章,评审
doi:10.1126/scitranslmed.3002493
更新日期:2011-11-30 00:00:00
abstract::Stimulator of interferon genes (STING) is a cytosolic receptor that senses both exogenous and endogenous cytosolic cyclic dinucleotides (CDNs), activating TBK1/IRF3 (interferon regulatory factor 3), NF-κB (nuclear factor κB), and STAT6 (signal transducer and activator of transcription 6) signaling pathways to induce r...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aaa4306
更新日期:2015-04-15 00:00:00
abstract::Antiretroviral therapy has improved the quality and length of life of millions of individuals affected by human immunodeficiency virus type 1 (HIV-1). The capacity of these drugs to indefinitely suppress HIV-which has a well-known capacity for escaping antiviral pressures-is surprising. In this issue of Science Transl...
journal_title:Science translational medicine
pub_type: 评论,杂志文章
doi:10.1126/scitranslmed.3002656
更新日期:2011-07-13 00:00:00
abstract::Despite the high clinical burden, little is known about pathophysiology underlying autism spectrum disorder (ASD). Recent resting-state functional magnetic resonance imaging (rs-fMRI) studies have found atypical synchronization of brain activity in ASD. However, no consensus has been reached on the nature and clinical...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aat9223
更新日期:2019-02-27 00:00:00
abstract::As the prevalence of Alzheimer's disease (AD) grows, so do the costs it imposes on society. Scientific, clinical, and financial interests have focused current drug discovery efforts largely on the single biological pathway that leads to amyloid deposition. This effort has resulted in slow progress and disappointing ou...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3008228
更新日期:2014-06-18 00:00:00
abstract::Improved understanding of the role of inflammation in tendon disease is required to facilitate therapeutic target discovery. We studied supraspinatus tendons from patients experiencing pain before and after surgical subacromial decompression treatment. Tendons were classified as having early, intermediate, or advanced...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aac4269
更新日期:2015-10-28 00:00:00
abstract::The amyloid-forming proteins tau, αB crystallin, and amyloid P protein are all found in lesions of multiple sclerosis (MS). Our previous work established that amyloidogenic peptides from the small heat shock protein αB crystallin (HspB5) and from amyloid β fibrils, characteristic of Alzheimer's disease, were therapeut...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3005681
更新日期:2013-04-03 00:00:00
abstract::Airway mucus in cystic fibrosis (CF) is highly elastic, but the mechanism behind this pathology is unclear. We hypothesized that the biophysical properties of CF mucus are altered because of neutrophilic oxidative stress. Using confocal imaging, rheology, and biochemical measures of inflammation and oxidation, we foun...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3010525
更新日期:2015-02-25 00:00:00
abstract::Retinal pigment epithelium (RPE) dysfunction and loss are a hallmark of non-neovascular age-related macular degeneration (NNAMD). Without the RPE, a majority of overlying photoreceptors ultimately degenerate, leading to severe, progressive vision loss. Clinical and histological studies suggest that RPE replacement str...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aao4097
更新日期:2018-04-04 00:00:00
abstract::About 25% of high-grade cervical intraepithelial neoplasias (CIN2/3) caused by human papillomavirus serotype 16 (HPV16) undergo complete spontaneous regression. However, to date, therapeutic vaccination strategies for HPV disease have yielded limited success when measured by their ability to induce robust peripheral b...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3007323
更新日期:2014-01-29 00:00:00
abstract::Venetoclax is a specific B cell lymphoma 2 (BCL-2) inhibitor with promising activity against acute myeloid leukemia (AML), but its clinical efficacy as a single agent or in combination with hypomethylating agents (HMAs), such as azacitidine, is hampered by intrinsic and acquired resistance. Here, we performed a genome...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aax2863
更新日期:2019-10-30 00:00:00
abstract::Physiological data are routinely recorded in intensive care, but their use for rapid assessment of illness severity or long-term morbidity prediction has been limited. We developed a physiological assessment score for preterm newborns, akin to an electronic Apgar score, based on standard signals recorded noninvasively...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3001304
更新日期:2010-09-08 00:00:00
abstract::Centronuclear myopathies (CNMs) are severe diseases characterized by muscle weakness and myofiber atrophy. Currently, there are no approved treatments for these disorders. Mutations in the phosphoinositide 3-phosphatase myotubularin (MTM1) are responsible for X-linked CNM (XLCNM), also called myotubular myopathy, wher...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aav1866
更新日期:2019-03-20 00:00:00
abstract::Parenteral and oral routes have been the traditional methods of administering cytotoxic agents to cancer patients. Unfortunately, the maximum potential effect of these cytotoxic agents has been limited because of systemic toxicity and poor tumor perfusion. In an attempt to improve the efficacy of cytotoxic agents whil...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3009951
更新日期:2015-02-04 00:00:00