Rituximab ameliorates anti-N-methyl-d-aspartate receptor encephalitis by removal of short-lived plasmablasts

Hachiya, Yasuo; Uruha, Akinori; Kasai-Yoshida, Emi; Shimoda, Konomi; Satoh-Shirai, Ikuko; Kumada, Satoko; Kurihara, Eiji; Suzuki, Kosuke; Ohba, Atsuko; Hamano, Shin‐ichiro; Sakuma, Hiroshi

doi:10.1016/j.jneuroim.2013.09.017

Cited by 49 publications

(35 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is no known ligand for CD20; functions of CD20 have been proposed to include calcium transport (33) and boosting of T cell-independent B cell responses (34). CD20-targeting therapies are commonly referred to as “B cell-depleting therapy”; accordingly, we also find the previously described significant impact of RTX on the B cell compartment, with long-term-depletion of memory B cells, early replenishment with naïve B cell phenotypes, and also reduction of plasmablasts, possibly owing to the higher turnover rates of short-lived plasmablasts (35, 36). We also show for the first time that normally rather infrequent CD19 + CD27-IgD − (double negative, DN) B cells become significantly depleted by RTX but at the same time comprise the majority of the small B cell population present in peripheral blood of RTX-treated patients; this may suggest relative resistance of DN B cells to CD20-targeted lymphocyte depleting therapy.…”

Section: Discussionsupporting

confidence: 82%

Rituximab Efficiently Depletes Increased CD20-Expressing T Cells in Multiple Sclerosis Patients

Palanichamy

Jahn

Nickles

et al. 2014

The Journal of Immunology

239

290

View full text Add to dashboard Cite

In multiple sclerosis (MS4) B cell depleting therapy using monoclonal anti-CD20 antibodies, including rituximab (RTX) and ocrelizumab (OCR), effectively reduces disease activity. Based on indirect evidence, it is generally believed that elimination of the antigen presenting capabilities and antigen non-specific immune functions of B cells underlie the therapeutic efficacy. However, a small subset of T lymphocytes (T cells) was shown to also express CD20, but controversy prevails surrounding the true existence of this T cell subpopulation. Using single-cell imaging flow cytometry and expression profiling of sorted lymphocyte subsets, we unequivocally demonstrate the existence of CD3+CD20dim T cells. We show that in MS patients increased levels of CD3+CD20dim T cells are effectively depleted by RTX. The pathological relevance of this T cell subset in MS remains to be determined. However, given their potential pro-inflammatory functionality, depletion of CD20-expressing T cells may also contribute to the therapeutic effect of RTX and other monoclonal antibodies targeting CD20.

show abstract

Section: Discussionsupporting

confidence: 82%

Rituximab Efficiently Depletes Increased CD20-Expressing T Cells in Multiple Sclerosis Patients

Palanichamy

Jahn

Nickles

et al. 2014

The Journal of Immunology

239

290

View full text Add to dashboard Cite

show abstract

“…Immune B cells and T cells are indispensable regulators and effectors in immune responses to the formation and development of anti‐NMDAR encephalitis (Camdessanché et al, ; Chen et al, ; Hachiya et al, ; Peng et al, ). However, how they enter the CNS compartment or the blood–brain barrier is undefined.…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid light and heavy neurofilament level increased in anti‐N‐methyl‐d‐aspartate receptor encephalitis

An³

et al. 2019

Brain and Behavior

View full text Add to dashboard Cite

Background Neurofilaments (Nf) are a series of highly specific scaffolding proteins of neurons. Neurofilament light chains (Nf‐L) and the heavy one (Nf‐H) are subunits of Nf, and they are recognized as potent productions of neural damage. The concentrations of Nf aggrandized significantly in neurological disease including neuromyelitis optica, multiple sclerosis, and Alzheimer's disease. However, whether Nf in cerebrospinal fluid (CSF) elevated in anti‐ N ‐methyl‐ d ‐aspartate receptor (NMDAR) encephalitis is unclear. Here, we aimed to detect whether CSF Nf is altered in NMDAR and whether changes in CSF Nf can serve as an objective and effective biomarker to evaluate disease severity and prognosis. Methods We collected 24 anti‐NMDAR encephalitis patients, 11 viral meningoencephalitis/encephalitis (VM) patients, and 21 controls in this study. CSF Nf‐L, Nf‐H, and cytokine levels (IL‐1β, IL‐6, and IL‐17A) were determined by enzyme‐linked immunosorbent assay (ELISA) and compared between groups. We evaluated patients’ clinical outcomes or prognosis according to modified Rankin scale (mRS) score. Results Compared with controls, both CSF Nf‐L and Nf‐H levels were significantly increased in anti‐NMDAR encephalitis patients. While compared with VM patients, only Nf‐L were increased in anti‐NMDAR encephalitis patients. Moreover, CSF Nf‐L were positively correlated with concentration of cytokines (IL‐1β, IL‐17A) and mRS scores in anti‐NMDAR encephalitis patients. After treatment, both CSF Nf‐L and Nf‐H levels decreased. Furthermore, the Nf‐L during follow‐up positively correlated with 3‐month mRS scores, and ΔNf‐L positively correlated with ΔmRS. Conclusions Briefly, CSF Nf‐L levels notably increased in anti‐NMDAR encephalitis patients in acute phase and positively correlated with disease severity. It could be considered as a useful indicator for clinical outcomes and prognosis.

show abstract

“…The therapeutic relevance of this fact for pedMS is underlined by the PB dependency of natalizumab and IFN-β treatment 31,33 mentioned above as well as by the significant reduction in PB in response to rituximab therapy. 39 …”

Section: Discussionmentioning

confidence: 99%

B-cell populations discriminate between pediatric- and adult-onset multiple sclerosis

Schwarz

Balint

Korporal-Kuhnke

et al. 2017

Neurol Neuroimmunol Neuroinflamm

View full text Add to dashboard Cite

Objective:To comparatively assess the B-cell composition in blood and CSF of patients with pediatric-onset multiple sclerosis (pedMS) and adult-onset multiple sclerosis (adMS).Methods:In this cross-sectional study, we obtained blood and CSF samples from 25 patients with pedMS (8–18 years) and 40 patients with adMS (23–65 years) and blood specimens from 66 controls (1–55 years). By using multicolor flow cytometry, we identified naive, transitional, isotype class-switched memory, nonswitched memory, and double-negative memory B-cell subsets as well as plasmablasts (PB) and terminally differentiated plasma cells (PC). Flow cytometric data were compared to concentrations of B-cell-specific cytokines in serum and CSF as determined by ELISA.Results:Frequencies of circulating naive B-cells decreased with higher age in controls but not in patients with multiple sclerosis (MS). B-cell patterns in CSF differed between pedMS and adMS with an acute relapse: in pedMS-derived CSF samples, high frequencies of nonswitched memory B cells and PB were present, whereas class-switched memory B cells and PC dominated in the CSF of patients with adMS. In pedMS, PB were also elevated in the periphery. Accumulation of PB in the CSF correlated with high intrathecal CXCL-13 levels and augmented intrathecal synthesis of immunoglobulin G and immunoglobulin M.Conclusions:We demonstrate distinct changes in intrathecal B-cell homeostasis in patients with pedMS during active disease, which differ from those in adults by an expansion of plasmablasts in blood and CSF and similarly occur in prototypic autoantibody-driven autoimmune disorders. This emphasizes the particular importance of activated B-lymphocyte subsets for disease progression in the earliest clinical stages of MS.

show abstract

Rituximab ameliorates anti-N-methyl-d-aspartate receptor encephalitis by removal of short-lived plasmablasts

Cited by 49 publications

References 10 publications

Rituximab Efficiently Depletes Increased CD20-Expressing T Cells in Multiple Sclerosis Patients

Rituximab Efficiently Depletes Increased CD20-Expressing T Cells in Multiple Sclerosis Patients

Cerebrospinal fluid light and heavy neurofilament level increased in anti‐N‐methyl‐d‐aspartate receptor encephalitis

B-cell populations discriminate between pediatric- and adult-onset multiple sclerosis

Contact Info

Product

Resources

About