scholarly journals Natalizumab concentrations during pregnancy in three patients with multiple sclerosis

2021 ◽  
pp. 135245852110521
Author(s):  
Alyssa A Toorop ◽  
Theo Rispens ◽  
Eva MM Strijbis ◽  
Bob W van Oosten ◽  
Brigit A de Jong ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Third Trimester ◽  
Blood Samples ◽  
The Third ◽  
Trough Concentrations ◽  
Active Multiple Sclerosis

In women with very active multiple sclerosis (MS), natalizumab can be continued during pregnancy to prevent rebound disease activity. Our aim was to evaluate changes in serum natalizumab trough concentrations during pregnancy. Blood samples of 3 patients were collected before, during, and after pregnancy. Natalizumab trough concentrations gradually decreased during pregnancy. The patient with the lowest trough concentrations during the third trimester was treated with extended interval dosing (EID). After delivery, natalizumab concentrations increased to similar levels as before pregnancy. All patients remained clinically and radiologically stable. MS neurologists should be aware of decreasing natalizumab concentrations during pregnancy, especially in patients with low initial trough concentrations and patients with EID.

Serum leptin levels during pregnancy in multiple sclerosis

2009 ◽  
Vol 15 (8) ◽  
pp. 907-912 ◽  
Author(s):  
RF Neuteboom ◽  
E Verbraak ◽  
JSA Voerman ◽  
M van Meurs ◽  
EAP Steegers ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Leptin Receptor ◽  
Late Pregnancy ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Third Trimester ◽  
Serum Leptin ◽  
The Third ◽  
Healthy Women

Background Disease activity in patients with multiple sclerosis (MS) is suppressed during pregnancy, whereas attack frequency increases after delivery. It is yet unclear, which immuno – endocrinological processes mediate these disease fluctuations. Leptin has been identified as a hormone that can influence inflammatory activity. Objective The aim of this study was to investigate whether pregnancy-induced fluctuations of serum leptin levels differed between patients with MS and controls and whether serum leptin levels correlate with periods of enhanced and diminished disease activity. Methods Women with MS and healthy women were prospectively followed during and after pregnancy. The MS group could be studied already at a timepoint before pregnancy. Serum leptin and soluble leptin receptor (SLR) levels were measured using enzyme-linked immunosorbent assay. Results Pre-pregnancy serum leptin levels were (mean ± SD) 22.9 ± 12.8 ng/ml in the MS group. These levels increased in the third trimester to 28.5 ± 15.0 ng/ml ( P = 0.007). The third trimester serum leptin levels in healthy women were comparable, 29.4 ± 19.0 ng/ml. Serum leptin levels after delivery dropped to 18.5 ± 12.8 ng/ml in women with MS ( P < 0.001) and to a lesser extend (22.0 ± 17.5 ng/ml) in healthy women ( P = 0.04). SLR levels showed the same pattern. Remarkably, women with the highest relative decrease in serum leptin levels after delivery had more often a postpartum relapse ( P = 0.008). Conclusion In women with MS, leptin increased during late pregnancy. A postdelivery drop in leptin levels was observed in both the MS and control group. The postdelivery drop was associated with the occurrence of postpartum relapse.

First trimester interleukin 8 levels are associated with postpartum relapse in multiple sclerosis

2009 ◽  
Vol 15 (11) ◽  
pp. 1356-1358 ◽  
Author(s):  
Rinze F Neuteboom ◽  
Evert Verbraak ◽  
Jane SA Voerman ◽  
Marjan van Meurs ◽  
Eric AP Steegers ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
High Risk ◽  
Disease Activity ◽  
Serum Levels ◽  
First Trimester ◽  
Interleukin 8 ◽  
Disease Course ◽  
Third Trimester ◽  
The Third

Pregnancy has an ameliorating effect on multiple sclerosis (MS), but directly after delivery the risk of a relapse is increased. The pro-inflammatory chemokine interleukin 8 is associated with disease activity. We aimed to investigate whether pregnancy-induced fluctuations of interleukin 8 correlate with periods of enhanced and diminished disease activity. Thirty-six women with MS were prospectively studied before, during and after pregnancy. Serum levels of interleukin 8 were significantly decreased during the third trimester (p = 0.03). High first trimester serum levels of interleukin 8 were associated with a high risk of postpartum relapse (p = 0.007). These results help us to further understand the altered disease course during pregnancy.

Variations in chemokine receptor and cytokine expression during pregnancy in multiple sclerosis patients

2006 ◽  
Vol 12 (4) ◽  
pp. 421-427 ◽  
Author(s):  
C López ◽  
M Comabella ◽  
M Tintoré ◽  
J Sastre-Garriga ◽  
X Montalban
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
Autoimmune Diseases ◽  
Disease Activity ◽  
Mrna Expression ◽  
Chemokine Receptors ◽  
Clinical Disease ◽  
Third Trimester ◽  
The Third

Although several T cell-mediated autoimmune diseases have shown a reduction in their clinical disease activity during pregnancy, the underlying mechanisms by which pregnancy causes such a beneficial effect on the disease activity are not fully understood. We performed a longitudinal study of chemokine receptors (CCR3, CCR4, CCR5, CXCR3, CXCR4) by flow cytometry in different subsets of peripheral blood mononuclear cells (PBMC) during pregnancy in multiple sclerosis (MS) patients. The levels of cytokine mRNA expression (IL-10, IFN-g) were also investigated by real-time quantitative reverse transcription polymerase chain reaction. The expression of CXCR3 by CD4 and CD8 positive T cells was decreased to a statistically significant extent during the second trimester of pregnancy. CD4 and CD8 T cells showed a statistically significant increase in the expression of CXCR4 during the third trimester of pregnancy. At the mRNA expression level, an increase in the IL-10/IFN-g ratio was observed during pregnancy, especially during the third trimester. These findings indicate immunomodulatory effects of pregnancy on the expression of chemokine receptors and cytokines, which may be related to changes in the clinical disease activity of T cell-mediated autoimmune diseases, such as MS.

The sFlt-1 to PlGF Ratio in Pregnant Women with Rheumatoid Arthritis: Impact of Disease Activity and Sulfasalazine Use

Rheumatology ◽  
2021 ◽  
Author(s):  
Rugina I Neuman ◽  
Hieronymus T W Smeele ◽  
A H Jan Danser ◽  
Radboud J E M Dolhain ◽  
Willy Visser
Keyword(s):  
Rheumatoid Arthritis ◽  
Cohort Study ◽  
Disease Activity ◽  
Pregnant Women ◽  
Gestational Age ◽  
Third Trimester ◽  
Low Disease Activity ◽  
The Third ◽  
Observational Prospective Cohort Study ◽  
Plgf Ratio

Abstract Objectives An elevated sFlt-1/PlGF-ratio has been validated as a significant predictor of preeclampsia, but has not been established in women with rheumatoid arthritis (RA). We explored whether the sFlt-1/PlGF-ratio could be altered due to disease activity in RA, and could be applied in this population to predict preeclampsia. Since sulfasalazine has been suggested to improve the angiogenic imbalance in preeclampsia, we also aimed to examine whether sulfasalazine could affect sFlt-1 or PlGF levels. Methods Making use of a nationwide, observational, prospective cohort study on pregnant women with RA, sFlt-1 and PlGF were measured in the third trimester. A total of 221 women, aged 21–42 years, were included, with a median gestational age of 30 + 3 weeks. Results No differences in sFlt-1 or PlGF were observed between women with high, intermediate or low disease activity (p= 0.07 and p= 0.41), whereas sFlt-1 and PlGF did not correlate with DAS28-CRP score (r=-0.01 and r=-0.05, respectively). Four (2%) women with a sFlt-1/PlGF-ratio ≤38 developed preeclampsia in comparison to three (43%) women with a ratio &gt; 38, corresponding to a negative predictive value of 98.1%. Sulfasalazine users (n = 57) did not show altered levels of sFlt-1 or PlGF in comparison to non-sulfasalazine users (n = 164, p= 0.91 and p= 0.11). Conclusion Our study shows that in pregnant women with RA, the sFlt-1/PlGF-ratio is not altered due to disease activity and a cut-off ≤38 can be used to exclude preeclampsia. Additionally, sulfasalazine use did not affect sFlt-1 or PlGF levels in this population.

scholarly journals The Potential Preventive Effect of Pregnancy and Breastfeeding on Multiple Sclerosis

2021 ◽  
Vol 84 (2) ◽  
pp. 71-84
Author(s):  
Mohsen Ali Alhomoud ◽  
Abdul Sattar Khan ◽  
Iftetah Alhomoud
Keyword(s):  
Multiple Sclerosis ◽  
Neurological Disease ◽  
Literature Search ◽  
Current Evidence ◽  
Obstetric Outcomes ◽  
Preventive Effect ◽  
Third Trimester ◽  
The Third ◽  
The Central Nervous System

<b><i>Background:</i></b> Multiple sclerosis (MS) is an inflammatory demyelinating chronic neurological disease that affects the central nervous system of young adults and their quality of life. Several studies have investigated the effects of pregnancy and breastfeeding on MS. However, the evidence regarding the influence of pregnancy and breastfeeding on MS is still accumulating. This review aimed to summarize the current evidence regarding the effects of pregnancy and breastfeeding on MS. <b><i>Summary:</i></b> A systematic electronic literature search of the PubMed and Embase databases was conducted to determine relevant published articles. The eligible studies were summarized and evaluated in tables. <b><i>Key Messages:</i></b> The majority of the studies indicated that pregnancy appears to lower the rate of MS relapses, particularly in the third trimester. The evidence regarding the effect of breastfeeding on MS remains inconsistent. Despite reports of negative obstetric outcomes in some pregnant women with MS, pregnancies in women with MS should not be categorized as high-risk pregnancies.

The monocyte transcriptome during pregnancy in multiple sclerosis: prominent expression of the Fc-receptor CD64

2010 ◽  
Vol 17 (4) ◽  
pp. 389-396 ◽  
Author(s):  
Rinze F Neuteboom ◽  
Evert Verbraak ◽  
Annet F Wierenga-Wolf ◽  
Jane SA Voerman ◽  
Marjan van Meurs ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cell Signalling ◽  
Immune Functions ◽  
Rt Pcr ◽  
Third Trimester ◽  
Fc Gamma Receptor ◽  
The Third ◽  
Gamma Receptor ◽  
Genes Expression ◽  
Biological Interest

Background: During the third trimester of pregnancy multiple sclerosis (MS) disease activity is reduced. It is not fully understood which factors mediate this disease amelioration.Objective: To study alterations of the monocyte transcriptome during pregnancy in MS patients, using a genomewide approach to identify differentially regulated genes.Methods: Women with MS and healthy controls were longitudinally studied, including a visit before pregnancy.Results: RNA-microarray analysis was performed in six patients. We found a significant increase of CD64 (Fc gamma receptor 1a, FcgR1a) during the third trimester compared with baseline, confirmed by RT-PCR in a group of ten patients. Analysis with Ingenuity software was performed using all genes expression of which was altered at least 1.5-fold in at least five out of six patients. Major networks that were altered during MS pregnancy were: cell-to-cell signalling and interaction, immune response, and cell signalling. From the genes selected for Ingenuity analysis, seven additional candidate genes, selected for their biological interest, were tested using RT-PCR in ten patients with MS and nine controls. We found an increased expression of JAK2 and STAT1 directly postpartum in patients with MS and in controls.Conclusion: The increased CD64 expression during pregnancy is indicative of enhanced innate immune functions.

Alterations of serum resistin in normal pregnancy and pre-eclampsia

2004 ◽  
Vol 108 (1) ◽  
pp. 81-84 ◽  
Author(s):  
Danqing CHEN ◽  
Minyue DONG ◽  
Qin FANG ◽  
Jing HE ◽  
Zhengping WANG ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Normal Pregnancy ◽  
Third Trimester ◽  
Resistin Level ◽  
Blood Samples ◽  
The Third ◽  
Maternal Adaptation ◽  
Serum Resistin Level ◽  
One Way Anova ◽  
Insight Into

Resistin is expressed in human placenta and has been postulated to play a role in regulating energy metabolism in pregnancy. However, changes in serum resistin levels in normal pregnancy and in the setting of pre-eclampsia are far from understood. The purpose of the present study was to clarify the alterations in serum resistin level in normal pregnancy and pre-eclampsia. Blood samples were taken from 28 healthy non-pregnant women, 27 women in the first, 26 in the second and 26 in the third trimesters of normal pregnancy and 25 women with pre-eclampsia. Serum resistin concentrations were determined by using an ELISA, and mean serum resistin levels were compared with one-way ANOVA. Serum resistin levels were not significantly different among non-pregnant women and women in the first and second trimesters of pregnancy (P>0.05 for all). Serum resistin was significantly elevated in the third trimester of normal pregnancy compared with non-pregnant women (P<0.01) and women in the first (P<0.001) and second (P<0.001) trimesters of pregnancy. Serum resistin level was significantly lower in women with pre-eclampsia than women in the third trimester of normal pregnancy (P<0.001), but was comparable with those of non-pregnant women and women in the first and second trimesters of pregnancy (P>0.05 for all). In conclusion, we found an increase in serum resistin in the third trimester of normal pregnancy, but this increase was not present in pre-eclampsia. We postulate that these associations may offer insight into the mechanisms of maternal adaptation to pregnancy and the pathogenesis of pre-eclampsia.

Osteopontin concentrations are increased in cerebrospinal fluid during attacks of multiple sclerosis

2010 ◽  
Vol 17 (1) ◽  
pp. 32-42 ◽  
Author(s):  
Lars Börnsen ◽  
Mohsen Khademi ◽  
Tomas Olsson ◽  
Per Soelberg Sørensen ◽  
Finn Sellebjerg
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Disease Activity ◽  
Cross Sectional Study ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cross Sectional ◽  
Blood Samples ◽  
Relapsing Remitting ◽  
Repeated Sampling ◽  
Csf Levels

Background:The cytokine osteopontin (OPN) is a potential key player in the immunopathogenesis of multiple sclerosis (MS) and a candidate biomarker for disease activity. Objective:The objective of this study was to examine concentrations of OPN in the cerebrospinal fluid (CSF) across the clinical spectrum of MS. Methods:Our research consisted of a cross-sectional study of patients from two randomized, placebo-controlled trials. Concentrations of OPN and other blood and CSF markers were determined using an enzyme-linked immunosorbent assay (ELISA). Samples were obtained from untreated patients with exacerbation of clinically isolated syndrome (CIS) ( n = 25) and relapsing–remitting MS (RRMS) ( n = 41) of whom 48 participated in clinical trials, randomly allocated to treatment with placebo or methylprednisolone (MP) and undergoing repeated sampling after 3 weeks. Furthermore, we obtained CSF and blood samples from patients with primary progressive MS (PPMS, n = 9), secondary progressive MS (SPMS, n = 28) and other neurological disorders (OND, n = 44), and blood samples from 24 healthy subjects. Results:OPN concentrations were significantly increased in the CSF of patients with CIS ( p = 0.02) and RRMS ( p < 0.001) in exacerbation compared to patients with OND, and increased levels of OPN were associated with high values of other biomarkers of inflammation. At 3-week follow-up CSF OPN concentrations had decreased significantly from baseline regardless treatment with placebo or MP. Patients with PPMS had increased OPN levels in the CSF ( p = 0.004) and high CSF levels of OPN were associated with high degrees of disability. Conclusions:OPN concentration in the CSF is a dynamic indicator of disease activity in RRMS, presumably reflecting ongoing inflammation. Increased CSF OPN concentrations in PPMS may indicate ongoing inflammation even in these patients.

Plasma corticotropin-releasing hormone, β-endorphin and cortisol inter-relationships during human pregnancy

1993 ◽  
Vol 128 (4) ◽  
pp. 339-344 ◽  
Author(s):  
Eng-Cheng Chan ◽  
Roger Smith ◽  
Terry Lewin ◽  
Max W Brinsmead ◽  
Hong-Ping Zhang ◽  
...  
Keyword(s):  
Cord Blood ◽  
Maternal Plasma ◽  
Corticotropin Releasing Hormone ◽  
Third Trimester ◽  
Blood Samples ◽  
Releasing Hormone ◽  
Human Pregnancy ◽  
The Third ◽  
Dynamic Relationships

To investigate the dynamic relationships among corticotropin-releasing hormone (CRH), β-endorphin (βEP), cortisol and obstetric events during pregnancy, blood samples were collected from 193 women at 28 weeks, 38 weeks, during labour and on the second postnatal day. Cord blood at delivery was also obtained. We found that: (1) Maternal plasma CRH, βEP and cortisol rose from 28 to 38 weeks. (2) During the third trimester maternal plasma CRH and βEP were correlated (r=0.30, p<0.001). (3) During labour, no correlations were found among maternal plasma CRH, βEP and cortisol. (4) Maternal CRH at labour and the duration of labour were not correlated. (5) Maternal plasma CRH tended to be higher in women who delivered early (more than seven days prior to estimated date of confinement [EDC]) relative to those who were on time (within seven days' EDC) or late (greater than seven days after EDC). (6) CRH in maternal plasma at labour and cord blood were correlated (r = 0.29, p<0.05) as were maternal and fetal βEP (r=0.43, p<0.001). (7) Fetal obstetric difficulty was correlated with fetal βEP (r=0.54, p<0.001). Our findings support the hypothesis that maternal plasma CRH regulates maternal βEP during the third trimester, but other factors are involved during labour and in response to maternal obstetric stress.

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