Natalizumab treatment decreases serum IgM and IgG levels in multiple sclerosis patients

2013 ◽  
Vol 19 (11) ◽  
pp. 1454-1461 ◽  
Author(s):  
Rebecca C Selter ◽  
Viola Biberacher ◽  
Verena Grummel ◽  
Dorothea Buck ◽  
Christian Eienbröker ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
B Cells ◽  
Plasma Cells ◽  
Serum Levels ◽  
Cross Sectional ◽  
Humanized Monoclonal Antibody ◽  
Natalizumab Treatment ◽  
Alpha4beta1 Integrin ◽  
Multiple Sclerosis Patients ◽  
The Impact

Background: Treatment with natalizumab, a humanized monoclonal antibody against alpha4beta1 integrin, is associated with an increase in lymphoid progenitor cells and B cells in peripheral blood. Objective: The objective of this study was to examine the impact of natalizumab therapy on serum levels of total IgG, IgA and IgM in patients with multiple sclerosis (MS). Methods: In two independent cross-sectional patient cohorts, serum levels of IgG, IgA and IgM were compared between patients treated with natalizumab and those not receiving natalizumab. Further, serum levels of IgG, IgA and IgM before and during natalizumab treatment were compared in two longitudinal patient cohorts. Results: In patients treated with natalizumab, serum IgM and IgG levels were significantly lower compared with therapy naïve patients ( p<0.0001). IgM levels significantly decreased after initiation of natalizumab treatment in both longitudinal patient cohorts ( p<0.01). Moreover, patients treated with natalizumab showed a time-dependent decrease in IgM levels during the first 2 years of treatment. Conclusion: Natalizumab treatment leads to a significant decrease in serum IgM and IgG levels in patients with MS. IgM levels decrease with treatment duration during the first 2 years of treatment. These findings might support the hypothesis that natalizumab interferes with homing of B cells, possibly leading to impaired differentiation into plasma cells and subsequently disturbed immunoglobulin synthesis.

scholarly journals JC Virus Seroprevalence and JCVAb Index in Polish Multiple Sclerosis Patients Treated with Immunomodulating or Immunosuppressive Therapies

2021 ◽  
Vol 10 (9) ◽  
pp. 1998
Author(s):  
Robert Bonek ◽  
Wojciech Guenter ◽  
Robert Jałowiński ◽  
Anna Karbicka ◽  
Anna Litwin ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Jc Virus ◽  
Dimethyl Fumarate ◽  
Risk Category ◽  
Seroprevalence Rate ◽  
Immunomodulatory Drugs ◽  
Cross Sectional ◽  
Treatment Type ◽  
Multiple Sclerosis Patients ◽  
The Impact

The use of a highly-effective treatment for multiple sclerosis (MS) is associated with a severe risk of developing complications, such as progressive multifocal leukoencephalopathy (PML) caused by the John Cunningham virus (JCV). The aim of this study was to evaluate the correlation between anti-JCV Ab seroprevalence, anti-JCV AI, demographic and clinical factors as well as the type of therapy used in the Polish MS population. This is a multicentre, prospective and cross-sectional study involving 1405 MS patients. The seroprevalence of anti-JCV Ab and anti-JCV AI levels as well as AI categories were analysed with the use of a second-generation two-step ELISA test (STRATIFY JCV DxSelect). The overall prevalence of anti-JCV Ab was 65.8%. It was shown that seroprevalence increases with the patient’s age. The seroprevalence was significantly associated with the treatment type, and the highest values (76%) were obtained from immunosuppressant-treated patients. Overall, 63.3% of seropositive patients had an antibody index (AI) level of >1.5. In the seropositive patient group, the mean AI level amounted to 2.09. Similarly to the seroprevalence, AI levels correlated with the patient’s age; AI level for patients above 40 years old and from subsequent age quintiles plateaued, amounting to at least 1.55. Patients treated with immunosuppressants and immunomodulatory drugs obtained the highest (1.67) and lowest (1.35) AI levels, respectively. Of the immunosuppressants used, the highest mean AI levels were observed in mitoxantrone and cladribine groups, amounting to 1.75 and 1.69, respectively. In patients treated with immunomodulatory drugs, the lowest AI levels were observed in the dimethyl fumarate (DMF) group (1.11). The seroprevalence rate in the Polish MS population is one of the highest in Europe. The majority of seropositive patients had an anti-JCV Ab level qualifying them for a high-risk category. The highest mean AI levels are observed in patients receiving immunosuppressants, especially mitoxantrone and cladribine. Patients receiving immunomodulatory drugs have lower AI levels compared to treatment-naïve subjects, especially when treated with DMF. Further studies, especially longitudinal studies, are required to determine the impact of MS drugs on the seroprevalence of anti-JCV Ab and AI levels.

Decreased soluble IFN-β receptor (sIFNAR2) in multiple sclerosis patients: A potential serum diagnostic biomarker

2016 ◽  
Vol 23 (7) ◽  
pp. 937-945 ◽  
Author(s):  
Teresa Órpez-Zafra ◽  
Jose Pavía ◽  
Isaac Hurtado-Guerrero ◽  
Maria J Pinto-Medel ◽  
Jose Luis Rodriguez Bada ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Serum Levels ◽  
Cross Sectional Study ◽  
First Year ◽  
Diagnostic Biomarker ◽  
Lower Serum ◽  
Cross Sectional ◽  
Treatment Naïve ◽  
Β Receptor ◽  
Multiple Sclerosis Patients

Background: The soluble isoform of the interferon-β (IFN-β) receptor (sIFNAR2) could modulate the activity of both endogenous and systemically administered IFN-β. Previously, we described lower serum sIFNAR2 levels in untreated multiple sclerosis (MS) than in healthy controls (HCs). Objective: To assess sIFNAR2 levels in a new cohort of MS patients and HCs, as well as in patients with clinically isolated syndrome (CIS) and with other inflammatory neurological disorders (OIND) and to assess its ability as a diagnostic biomarker. Methods: The cross-sectional study included 148 MS (84 treatment naive and 64 treated), 87 CIS, 42 OIND, and 96 HCs. Longitudinal study included 94 MS pretreatment and after 1 year of therapy with IFN-β, glatiramer acetate (GA), or natalizumab. sIFNAR2 serum levels were measured by a quantitative ELISA developed and validated in our laboratory. Results: Naive MS and CIS patients showed significantly lower sIFNAR2 levels than HCs and OIND patients. The sensitivity and specificity to discriminate between MS and OIND, for a sIFNAR2 cutoff value of 122.02 ng/mL, were 70.1%, and 79.4%, respectively. sIFNAR2 increased significantly in IFN-β-treated patients during the first year of therapy in contrast to GA- and natalizumab-treated patients who showed non-significant changes. Conclusion: The results suggest that sIFNAR2 could be a potential diagnostic biomarker for MS.

scholarly journals Reduced peripheral blood regulatory B cell levels are not associated with the Expanded Disability Status Scale score in multiple sclerosis

2018 ◽  
Vol 46 (9) ◽  
pp. 3970-3978 ◽  
Author(s):  
Shujun Guo ◽  
Qingqing Chen ◽  
Xiaoli Liang ◽  
Mimi Mu ◽  
Jing He ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
B Cells ◽  
Peripheral Blood ◽  
Plasma Cells ◽  
Serum Levels ◽  
Memory B Cells ◽  
Healthy Controls ◽  
Expanded Disability Status Scale ◽  
Disability Status ◽  
Edss Score

Objective To investigate levels of regulatory B (Breg) cells, plasma cells, and memory B cells in the peripheral blood, and interleukin (IL)-10 in the serum of multiple sclerosis (MS) patients, and to determine the correlation between Breg cell levels and the Expanded Disability Status Scale (EDSS) score. Methods Levels of Breg cells, plasma cells, and memory B cells in the peripheral blood of 12 MS patients were measured using flow cytometry. IL-10 serum levels were measured by enzyme-linked immunosorbent assay. The correlation between Breg cell levels and MS EDSS score was measured using Pearson’s correlation coefficient. Results Compared with healthy controls, MS patients had decreased levels of CD19+CD24hiCD38hi Breg cells in their peripheral blood and reduced serum levels of IL-10; however, the ratios of CD19+CD27hiCD38hi plasma cells and CD19+CD27+CD24hi memory B cells to total B cells did not differ significantly between healthy controls and MS patients. CD19+CD24hiCD38hi Breg cell levels in the peripheral blood of MS patients were not significantly correlated with MS EDSS score. Conclusion Peripheral blood CD19+CD24hiCD38hi Breg cell levels and serum IL-10 levels were reduced in MS patients compared with controls, but Breg cell levels were not correlated with MS EDSS score.

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

2016 ◽  
Vol 4 (1) ◽  
pp. e309 ◽  
Author(s):  
Alexander Schwarz ◽  
Bettina Balint ◽  
Mirjam Korporal-Kuhnke ◽  
Sven Jarius ◽  
Kathrin von Engelhardt ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
B Cells ◽  
B Cell ◽  
B Lymphocyte ◽  
Plasma Cells ◽  
Cross Sectional Study ◽  
Memory B Cells ◽  
Immunoglobulin M ◽  
Adult Onset ◽  
Cross Sectional

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.

scholarly journals Epstein-Barr Virus Specific Antibody Response in Multiple Sclerosis Patients during 21 Months of Natalizumab Treatment

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Massimiliano Castellazzi ◽  
Serena Delbue ◽  
Francesca Elia ◽  
Matteo Gastaldi ◽  
Diego Franciotta ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Specific Antibody ◽  
Epstein Barr Virus ◽  
Serum Levels ◽  
Nuclear Antigen ◽  
Barr Virus ◽  
Natalizumab Treatment ◽  
Virus Specific Antibody ◽  
Epstein Barr ◽  
Multiple Sclerosis Patients

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. Natalizumab, a humanized anti-α4 integrin monoclonal antibody, is a highly effective treatment approved for MS. An association between MS and an exposure to Epstein-Barr Virus (EBV) sustained by the levels of antiviral capsid antigen (VCA) and anti-Epstein-Barr nuclear antigen-1 (EBNA-1) IgG has been described. Our goal was to verify the utility of EBV-specific IgG as a marker in Natalizumab treated MS. Twenty patients (17 female and 3 male) in treatment with Natalizumab were enrolled. Serum levels of anti-VCA and anti-EBNA-1 IgG were determined and expressed as arbitrary units (AU) before treatment and every three months for 21 months of therapy. Anti-VCA IgG levels were increased at the 15th month (235410 ± 196712 AU) comparing with the 3rd (98146 ± 47145 AU) and the 6th (109866 ± 52270 AU) months of therapyp<0.05. No significant differences were found for serum anti-EBNA-1 IgG levels. Our data indicate that a transient, self-limited, EBV reactivation can occur in MS during Natalizumab therapy but our results do not support the use of serum EBV-specific antibody levels as biomarkers for monitoring therapeutic response to Natalizumab in the course of MS.

scholarly journals Fingolimod alters intrathecal B cell maturation in multiple sclerosis patients

2020 ◽  
Author(s):  
Markus C. Kowarik ◽  
David Astling ◽  
Gildas Lepennetier ◽  
Alanna Ritchie ◽  
Bernhard Hemmer ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
B Cells ◽  
B Cell ◽  
Peripheral Blood ◽  
Clonal Expansion ◽  
Cell Maturation ◽  
Lymphocyte Migration ◽  
B Cell Maturation ◽  
Natalizumab Treatment ◽  
Multiple Sclerosis Patients

Abstract Background: B cells are postulated to play multiple roles in the pathogenesis of multiple sclerosis (MS) including pathogenic antibody production, antigen-presentation and pro-inflammatory cytokine secretion. Natalizumab and fingolimod are effective MS therapies that disrupt lymphocyte migration but exert differential effects on B cell maturation and trafficking. Herein, we investigated their effects on peripheral blood and cerebrospinal fluid (CSF) B cell repertoires.Methods: Paired CSF and peripheral blood (PB) lymphocytes were collected from MS patients at baseline and after 6 months of treatment with fingolimod (n = 4) or natalizumab (n = 4). B cell subsets including naïve, CD27+ memory, CD27-IgD- double-negative B cells and plasmablasts were collected by FACS and their respective heavy-chain variable region (VH) repertoires assessed by next generation deep sequencing (Illumina MiSeq).Results: Treatment with fingolimod lead to a distinct contraction of the PB B cell pool whereas natalizumab resulted in an expansion of circulating PB B cells. In contrast, CSF B cell numbers remained stable under treatment with fingolimod but decreased following natalizumab therapy. Clonal overlap between CSF and peripheral blood B cells was reduced following natalizumab treatment (-24% reduction of clonal groups) but remained stable with fingolimod therapy. Lineage analyses of CSF B cell repertoires at baseline and following therapy revealed large, clonally expanded B cell clusters in natalizumab-treated MS patients but no intrathecal clonal expansion following fingolimod therapy. Conclusions: Our findings suggest that natalizumab treatment diminishes the exchange of peripheral and intrathecal B cells but does not impact intrathecal clonal expansion. In contrast, fingolimod treatment fails to alter B cell exchange across the blood-brain-barrier but affects intrathecal clonal expansion. Sphingosine-1 phosphate receptor inhibition may impact MS disease progression by inhibiting intrathecal germinal center activity.

scholarly journals The Impact of Vitamin D Low Doses on Its Serum Level and Cytokine Profile in Multiple Sclerosis Patients

2021 ◽  
Vol 10 (13) ◽  
pp. 2781
Author(s):  
Anna Walawska-Hrycek ◽  
Weronika Galus ◽  
Eugeniusz Hrycek ◽  
Aleksandra Kaczmarczyk ◽  
Ewa Krzystanek
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Low Dose ◽  
Serum Levels ◽  
Vitamin D Supplementation ◽  
Cytokine Profile ◽  
Low Doses ◽  
Anti Inflammatory ◽  
Multiple Sclerosis Patients ◽  
The Impact

Vitamin D is known to have immunomodulatory properties and its deficiency is identified as an environmental risk factor for the development of autoimmune diseases, including multiple sclerosis. The aim of this study was to assess whether low-dose vitamin D supplementation could normalize the 25(OH)D serum levels in patients with relapsing-remitting multiple sclerosis (RRMS) and vitamin D deficiency (serum 25(OH)D < 75 nmol/L), and whether it may impact serum levels of selected cytokines. Among 44 patients (mean age 38.4 ± 10.1 years, 33 women and 11 men), after 12 months of low-dose vitamin D supplementation, serum levels of 25(OH)D normalized in 34 (77.3%) of the patients. Together with vitamin D increase, median levels of anti-inflammatory cytokines (IL10, TGF-β) and regulatory IFN-γ increased, while proinflammatory IL-17 remained unchanged. Moreover, an increase of inorganic phosphorus levels and decrease of PTH levels were observed, but without changes in total calcium concentration. These results may indicate that long-term supplementation with low doses of vitamin D is sufficient to compensate its deficiency in patients with RRMS and may help to maintain beneficial anti-inflammatory cytokine profile.

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