Match!

Failed B cell survival factor trials support the importance of memory B cells in multiple sclerosis

Published on Feb 1, 2020in European Journal of Neurology4.387
路 DOI :10.1111/ene.14105
David Baker156
Estimated H-index: 156
(QMUL: Queen Mary University of London),
Gareth Pryce40
Estimated H-index: 40
(QMUL: Queen Mary University of London)
+ 2 AuthorsGavin Giovannoni75
Estimated H-index: 75
(QMUL: Queen Mary University of London)
Abstract
  • References (30)
  • Citations (0)
馃摉 Papers frequently viewed together
1 Citations
20009.94Leukemia
3 Authors (J. M. D. Plate, ..., S. B. Kelkar)
17 Citations
35 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
References30
Newest
#1Amy E. Lovett-Racke (The Ohio State University Wexner Medical Center)H-Index: 31
#2Matthew G. Gormley (The Ohio State University Wexner Medical Center)H-Index: 1
Last. Edward Fox (University of Texas at Austin)H-Index: 27
view all 13 authors...
Abstract Multiple sclerosis (MS) is a demyelinating disease of the central nervous system, thought to be mediated by myelin-specific CD4+ T cells. However, B cell depletion has proven to be an effective therapy for MS, but the mechanism is not well understood. This study was designed to determine how B cell depletion changes lymphocyte profiles. During a phase IIa clinical trial with ublituximab, a novel CD20 antibody, blood was collected from 48 MS patients at 11 time points over 24鈥痺eeks and t...
1 CitationsSource
#1Laurie BaertH-Index: 2
#2Mahdia Benkhoucha (University of Geneva)H-Index: 13
Last. Bertrand HuardH-Index: 21
view all 26 authors...
Objective: The two related tumor necrosis factor members a proliferation-inducing ligand (APRIL) and B-cell activation factor (BAFF) are currently targeted in autoimmune diseases as B-cell regulators. In multiple sclerosis (MS), combined APRIL/BAFF blockade led to unexpected exacerbated inflammation in the central nervous system (CNS) of patients. Here, we investigate the role of the APRIL/BAFF axis in the CNS. Methods: APRIL expression was analyzed in MS lesions by immunohistochemistry. The in ...
3 CitationsSource
#1Daniel Ramsk枚ld (Karolinska University Hospital)H-Index: 16
#2Ioannis Parodis (Karolinska University Hospital)H-Index: 6
Last. Vivianne Malmstr枚m (Karolinska University Hospital)H-Index: 38
view all 14 authors...
Abstract Background Systemic lupus erythematosus (SLE) is a systemic autoimmune disease, which exhibits multiple B cell abnormalities including expanded populations of memory B cells and elevated levels of autoantibodies. Belimumab is a monoclonal antibody targeting the B cell cytokine BAFF (a.k.a. BLyS), approved for the treatment of SLE. Methods In this prospective cohort study, B cells from peripheral blood of 23 SLE patients initiating belimumab treatment and followed longitudinally for up t...
3 CitationsSource
#1Yu-Tzu Tai (Harvard University)H-Index: 69
#2Liang Lin (Harvard University)H-Index: 2
Last. Kenneth C. Anderson Broyl (Harvard University)H-Index: 162
view all 13 authors...
We investigate here how APRIL impacts immune regulatory T cells and directly contributes to the immunosuppressive multiple myeloma (MM) bone marrow (BM) microenvironment. First, APRIL receptor TACI expression is significantly higher in regulatory T cells (Tregs) than conventional T cells (Tcons) from the same patient, confirmed by upregulated Treg markers, i.e., Foxp3, CTLA-4. APRIL significantly stimulates proliferation and survival of Tregs, whereas neutralizing anti-APRIL monoclonal antibodie...
5 CitationsSource
#1Diana Celeste Salazar-Camarena (University of Guadalajara)H-Index: 3
Last. C.A. Palafox-S谩nchez (University of Guadalajara)H-Index: 11
view all 9 authors...
Abstract Background Systemic lupus erythematosus (SLE) is the prototype of systemic autoimmune disease, characterized by loss of immune tolerance against self-antigens where autoantibody production is the hallmark of disease. B-cell-activating factor (BAFF) and A proliferation-inducing ligand (APRIL) are cytokines that promote autoreactive cell survival, immunoglobulin-class switching and autoantibody responses in human and mouse SLE models. BAFF and APRIL exert their functions through interacti...
1 CitationsSource
#1Laurie Baert (French Institute of Health and Medical Research)H-Index: 2
#2Benoit Manfroi (French Institute of Health and Medical Research)H-Index: 5
Last. Bertrand Huard (French Institute of Health and Medical Research)H-Index: 9
view all 5 authors...
Abstract Autoimmunity occurs when an adaptive immune response is directed against a self-antigen. As such, autoimmune reactions associated with the production of autoantibodies are common. These autoantibodies may either be pathogenic by inducing the initial damage to self, or exacerbate the reaction secondarily to the initial damage. In both cases, the pathway(s) leading to exposure of the immune system to the self-antigen inducing the production of autoantibodies is largely unknown. The latter...
3 CitationsSource
#1David Baker (QMUL: Queen Mary University of London)H-Index: 156
#2Gareth Pryce (QMUL: Queen Mary University of London)H-Index: 40
Last. Klaus Schmierer (QMUL: Queen Mary University of London)H-Index: 31
view all 5 authors...
Although many suspected autoimmune diseases are thought to be T cell-mediated, the response to therapy indicates that depletion of B cells consistently inhibits disease activity. In multiple sclerosis, it appears that disease suppression is associated with the long-term reduction of memory B cells, which serves as a biomarker for disease activity in many other CD20+ B cell depletion-sensitive, autoimmune diseases. Following B cell depletion, the rapid repopulation by transitional (immature) and ...
7 CitationsSource
#1Weiqing HuangH-Index: 15
#2Tam D. QuachH-Index: 4
Last. Anne DavidsonH-Index: 40
view all 15 authors...
4 CitationsSource
#1Edgar Meinl (LMU: Ludwig Maximilian University of Munich)H-Index: 55
#2Franziska S. Thaler (LMU: Ludwig Maximilian University of Munich)H-Index: 5
Last. Stefan F. Lichtenthaler (TUM: Technische Universit盲t M眉nchen)H-Index: 34
view all 3 authors...
Proteolytic shedding of the receptors BCMA, TACI, and BAFFR reduces their cell-surface expression and ligand-mediated survival of B cell subsets. This shedding is executed by protease 纬-secretase or by metalloproteases, and is partially dependent on ligand binding and receptor interactions. Shed receptors may serve as biomarkers for autoimmunity and lymphoma.
4 CitationsSource
#1Elisabeth Schuh (LMU: Ludwig Maximilian University of Munich)H-Index: 8
#2Andrea Musumeci (LMU: Ludwig Maximilian University of Munich)H-Index: 2
Last. Edgar Meinl (LMU: Ludwig Maximilian University of Munich)H-Index: 55
view all 8 authors...
The BAFF-APRIL system is best known for its control of B cell homeostasis, and it is a target of therapeutic intervention in autoimmune diseases and lymphoma. By analyzing the expression of the three receptors of this system, B cell maturation Ag (BCMA), transmembrane activator and CAML interactor, and BAFF receptor, in sorted human immune cell subsets, we found that BCMA was transcribed in plasmacytoid dendritic cells (pDCs) in both blood and lymphoid tissue. Circulating human pDCs contained BC...
12 CitationsSource
Cited By0
Newest