The expression of integrins on activated T-cells in multiple sclerosis. Effect of intravenous methylprednisolone treatment

1998 ◽  
Vol 4 (3) ◽  
pp. 239-242 ◽  
Author(s):  
S Luján ◽  
J Masjuan ◽  
E Roldán ◽  
L M Villar ◽  
P González-Porqué ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Total Population ◽  
Intravenous Methylprednisolone ◽  
Activated T Cells ◽  
Mean Intensity ◽  
T Cell Migration ◽  
Relapsing Remitting ◽  
Methylprednisolone Treatment ◽  
The Mean

We studied the effect of intravenous methylprednisolone (MP) on the expression of the integrins, LFA-1 and VLA-4, on activated blood T-lymphocytes in 17 patients with relapses of clinically definite relapsing-remitting MS. MP treatment did not induce changes in the expression of CD3, CD4, DR, LFA-1 or VLA-4 markers when measured in the total population of lymphocytes in MS patients in relation to treatment. Treatment influenced neither the LFA-1 nor VLA-4 positive cells within the CD3+ population. MP treatment clearly decreased the DR+ CD3+ cells (P50.01) and the percentage of DR+ CD3+ lymphocytes bearing VLA-4 (P50.01). However, this was not the case when we studied the percentage of lymphocytes which expressed LFA-1. Glucocorticoids did not influence the mean intensity of the expression of the two integrins quantified in either total or DR+ CD3+ lymphocytes. Although, further research seems warranted to investigate a possible effect of MP on lymphocyte integrin function, this work corroborates the idea that MP treatment may interfere with the mechanisms of T-cell migration into CNS, thus modulating the activity of multiple sclerosis.

The expression of integrins on activated T-cells in multiple sclerosis. Effect of intravenous methylprednisolone treatment

1998 ◽  
Vol 4 (3) ◽  
pp. 239-242
Author(s):  
S. Luján ◽  
J. Masjuan ◽  
E. Roldán ◽  
L.M. Villar ◽  
P. González-Porqué ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Intravenous Methylprednisolone ◽  
Activated T Cells ◽  
Methylprednisolone Treatment

Myelin basic protein in CSF as indicator of disease activity in multiple sclerosis

1998 ◽  
Vol 4 (3) ◽  
pp. 124-126 ◽  
Author(s):  
K JB Lamers ◽  
H PM de Reus ◽  
P JH Jongen
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Myelin Basic Protein ◽  
Basic Protein ◽  
Normal Values ◽  
Disease Process ◽  
Intravenous Methylprednisolone ◽  
Relapsing Remitting ◽  
Methylprednisolone Treatment ◽  
Edss Score

There is an evident need for a quantitative laboratory marker for ascertaining disease activity and treatment effects in multiple sclerosis (MS) patients. Activity of the disease process in MS is accompanied by myelin breakdown and appearance of myelin basic protein (MBP) in cerebrospinal fluid (CSF). In this paper MBP in CSF of relapsing-remitting (RR) MS patients is reviewed. MBP in CSF is a fragment containing an epitope corresponding to aminoacid residues 45-89 of the native molecule. From several relevant studies about CSF MBP in RR MS the following relations can be concluded: CSF MBP levels in active MS patients are frequently increased (45-100%), remain increased until 5 to 6 weeks after onset symptoms and are higher in polysymptomatic exacerbations and correlate with number of gadolinium-enhanced (Gd) lesions on MRI, severity of relapses, EDSS score and CSF intrathecal IgM synthesis. After an intravenous methylprednisolone treatment the increased CSF MBP levels return to normal values and reduction in CSF MBP is related to reduction in EDSS score, number of Gd lesions and CSF intrathecal IgM synthesis.

Effect of monthly intravenous cyclophosphamide in rapidly deteriorating multiple sclerosis patients resistant to conventional therapy

2001 ◽  
Vol 7 (3) ◽  
pp. 185-188 ◽  
Author(s):  
Omar A Khan ◽  
Marina Zvartau-Hind ◽  
Christina Caon ◽  
Moeen U Din ◽  
Mickey Cochran ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Conventional Therapy ◽  
Clinical Deterioration ◽  
Intravenous Methylprednisolone ◽  
Intravenous Cyclophosphamide ◽  
Relapsing Remitting ◽  
Methylprednisolone Treatment ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Clinical Worsening

Fourteen consecutive clinically definite relapsing-remitting multiple sclerosis (MS) patients were treated with monthly intravenous cyclophosphamide (CTX) for 6 months. All had experienced severe clinical deterioration during the 12 months prior to treatment with CTX despite treatment with conventional immunomodulating agents and intravenous methylprednisolone. Treatment with CTX led to improvement and neurologic stability within 6 months which was sustained for at least 18 months after the onset of treatment with CTX. Therapy with CTX was well tolerated. CTX may be of benefit in MS patients who experience rapid clinical worsening and are resistant to conventional therapy.

scholarly journals Novel self-amplificatory loop between T cells and tenocytes as a driver of chronicity in tendon disease

2021 ◽  
pp. annrheumdis-2020-219335
Author(s):  
Emma Garcia-Melchor ◽  
Giacomo Cafaro ◽  
Lucy MacDonald ◽  
Lindsay A N Crowe ◽  
Shatakshi Sood ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Migration ◽  
T Cell ◽  
Inflammatory Cytokines ◽  
T Cell Activation ◽  
Cell Activation ◽  
Conditioned Media ◽  
Tissue Remodelling ◽  
Activated T Cells ◽  
T Cell Migration

ObjectivesIncreasing evidence suggests that inflammatory mechanisms play a key role in chronic tendon disease. After observing T cell signatures in human tendinopathy, we explored the interaction between T cells and tendon stromal cells or tenocytes to define their functional contribution to tissue remodelling and inflammation amplification and hence disease perpetuation.MethodsT cells were quantified and characterised in healthy and tendinopathic tissues by flow cytometry (FACS), imaging mass cytometry (IMC) and single cell RNA-seq. Tenocyte activation induced by conditioned media from primary damaged tendon or interleukin-1β was evaluated by qPCR. The role of tenocytes in regulating T cell migration was interrogated in a standard transwell membrane system. T cell activation (cell surface markers by FACS and cytokine release by ELISA) and changes in gene expression in tenocytes (qPCR) were assessed in cocultures of T cells and explanted tenocytes.ResultsSignificant quantitative differences were observed in healthy compared with tendinopathic tissues. IMC showed T cells in close proximity to tenocytes, suggesting tenocyte–T cell interactions. On activation, tenocytes upregulated inflammatory cytokines, chemokines and adhesion molecules implicated in T cell recruitment and activation. Conditioned media from activated tenocytes induced T cell migration and coculture of tenocytes with T cells resulted in reciprocal activation of T cells. In turn, these activated T cells upregulated production of inflammatory mediators in tenocytes, while increasing the pathogenic collagen 3/collagen 1 ratio.ConclusionsInteraction between T cells and tenocytes induces the expression of inflammatory cytokines/chemokines in tenocytes, alters collagen composition favouring collagen 3 and self-amplifies T cell activation via an auto-regulatory feedback loop. Selectively targeting this adaptive/stromal interface may provide novel translational strategies in the management of human tendon disorders.

scholarly journals Disease phenotype analyses of relapsing-remitting multiple sclerosis in Canada and Saudi Arabia

2015 ◽  
Vol 42 (S1) ◽  
pp. S32-S32
Author(s):  
M Alluqmani ◽  
M Alqermli ◽  
G Blevins ◽  
B Alotibi ◽  
F Giuliani ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Saudi Arabia ◽  
Geographic Location ◽  
Clinical Findings ◽  
Cross Sectional ◽  
Relapsing Remitting ◽  
Similar Disease ◽  
The Mean ◽  
Sectional Analysis ◽  
Relapsing Remitting Multiple Sclerosis

Background: Multiple sclerosis (MS) exhibits a spectrum of clinical findings, especially in relapsing-remitting MS (RR-MS). To assess the effects of geographic location and ethnicity on RR-MS phenotype, we investigated RR-MS patients in Canada and Saudi Arabia. Methods: A retrospective cross-sectional analysis of patients receiving active care in MS Clinics was performed in Medina, Saudi Arabia and Edmonton, Alberta. Demographic and clinical data was collected for each patient. Results: 98 patients with treated RR-MS were recruited (n=51, Medina; n=47, Edmonton); 40 patients were Caucasian (Edmonton) while 46 patients were Bedouin (Medina). Although the disease duration was longer in the Edmonton (5.7+2.3 yr) compared to the Medina group (4.4+1.4 yr) (p<0.05), the mean age of RR-MS onset, relapse rate and EDSS change were similar. The female:male ratio was comparable in Edmonton (35:12) and Medina (32:19), as was the risk of optic neuritis. The likelihood of an infratentorial lesion-associated presentation differed (Edmonton, n=23; Medina; n=13) among groups (p<0.05). Spinal cord lesions on MRI were more frequent in Edmonton (n=18) compared to Medina (n=1) patients (p<0.05). Conclusions: Despite differences in location, ethnicity, and a predominance of infratentorial lesion burden the Edmonton group, the RR-MS phenotype displayed similar disease severity and trajectory in these cohorts.

CRYAB modulates the activation of CD4+ T cells from relapsing–remitting multiple sclerosis patients

2013 ◽  
Vol 19 (14) ◽  
pp. 1867-1877 ◽  
Author(s):  
Que Lan Quach ◽  
Luanne M Metz ◽  
Jenna C Thomas ◽  
Jonathan B Rothbard ◽  
Lawrence Steinman ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Cytokine Production ◽  
Clinical Signs ◽  
Healthy Controls ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Background: Suppression of activation of pathogenic CD4+ T cells is a potential therapeutic intervention in multiple sclerosis (MS). We previously showed that a small heat shock protein, CRYAB, reduced T cell proliferation, pro-inflammatory cytokine production and clinical signs of experimental allergic encephalomyelitis, a model of MS. Objective: We assessed whether the ability of CRYAB to reduce the activation of T cells translated to the human disease. Methods: CD4+ T cells from healthy controls and volunteers with MS were activated in vitro in the presence or absence of a CRYAB peptide (residues 73–92). Parameters of activation (proliferation rate, cytokine secretion) and tolerance (anergy, activation-induced cell death, microRNAs) were evaluated. Results: The secretion of pro-inflammatory cytokines by CD4+ T cells was decreased in the presence of CRYAB in a subset of relapsing–remitting multiple sclerosis (RRMS) participants with mild disease severity while no changes were observed in healthy controls. Further, there was a correlation for higher levels of miR181a microRNA, a marker upregulated in tolerant CD8+ T cells, in CD4+ T cells of MS patients that displayed suppressed cytokine production (responders). Conclusion: CRYAB may be capable of suppressing the activation of CD4+ T cells from a subset of RRMS patients who appear to have less disability but similar age and disease duration.

Prospective study of multiple sclerosis with early onset

2002 ◽  
Vol 8 (2) ◽  
pp. 115-118 ◽  
Author(s):  
A Ghezzi ◽  
C Pozzilli ◽  
M Liguori ◽  
M G Marrosu ◽  
N Milani ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
First Year ◽  
Hormonal Changes ◽  
Disability Status ◽  
Definite Multiple Sclerosis ◽  
Relapsing Remitting ◽  
Clinically Definite Multiple Sclerosis ◽  
The Mean ◽  
And Gender

Fifty-four subjects (36 females and 18 males) affected by clinically definite multiple sclerosis (MS) and with onset of the disease at 15 years of age or before were prospectively studied in five Italian MS centres. Female/male ratio was 4.7 in subjects with age ≥12 years, suggesting a role of hormonal changes in triggering MS onset. The mean follow-up duration was 10.9-5.6 years. The functional systems more frequently involved at onset were the pyramidal and brainstem (both in 28% of cases). The onset was monosymptomatic in 31 subjects (57%). The course was relapsing-remitting in 39 subjects (72%) and relapsing-progressive in 15 (28%). Disability was assessed by the Expanded Disability Status Scale (EDSS): the mean score after 8 years of follow up was 3.5 (-2.5). The score was <4 in 68% of cases, between 4 and 6 in 8% of cases, > 6 in 24% of cases. Disability after 8 years was highly predicted by disability in the first year (p=0.008). There was a tendency to a worse prognosis in relation to the number of relapses in the first 2 years (p=0.08). The outcome was not influenced by the characteristics of symptoms at onset, age and gender.

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