Long-term therapy with glatiramer acetate in multiple sclerosis: effect on T-cells

2001 ◽  
Vol 7 (1) ◽  
pp. 43-47 ◽  
Author(s):  
Samia Ragheb ◽  
Sarah Abramczyk ◽  
Deena Lisak ◽  
Robert Lisak
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Glatiramer Acetate ◽  
Mechanisms Of Action ◽  
Term Therapy ◽  
In Vitro Proliferation ◽  
Long Term Therapy

Glatiramer acetate (GA) is an immunotherapeutic drug for multiple sclerosis (MS). Several mechanisms of action have been demonstrated which target and affect T-cells that are specific for myelin antigen epitopes. We measured the in vitro proliferation of GA-responsive T-cells from untreated MS patients and from normal healthy subjects; in addition, we determined the effect of prolonged GA therapy or interferon-b therapy on the in vitro proliferation of GA-responsive T-cells of MS patients. We found that GA induces the proliferation of T-cells isolated from individuals who have not been previously exposed to GA, and that long-term in vivo therapy of MS patients with GA abrogates the GA-induced proliferative response of T-cells. In GA-treated patients, there is no evidence of generalized immunosuppression; both tetanus toxoid and anti-CD3 induced proliferative responses remain unaffected. We propose that prolonged in vivo exposure to GA may result in the eventual induction of anergy or deletion of a population of GA-responsive cells that may also be T-cells that are pathogenic in MS. This mechanism of action, in addition to other mechanisms that have been demonstrated, suggests that GA has pleiotropic effects on the immune system in MS.

Long-term therapy with glatiramer acetate in multiple sclerosis: effect on T-cells

2001 ◽  
Vol 7 (1) ◽  
pp. 43-47 ◽  
Author(s):  
S. Ragheb ◽  
S. Abramczyk ◽  
D. Lisak ◽  
R. Lisak
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Glatiramer Acetate ◽  
Term Therapy ◽  
Long Term Therapy

T cell-T cell activation in multiple sclerosis

1997 ◽  
Vol 3 (4) ◽  
pp. 238-242 ◽  
Author(s):  
JW Lindsey ◽  
RH Kerman ◽  
JS Wolinsky
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Viral Infections ◽  
Activated T Cells ◽  
In Vitro Proliferation

Activated T cells are able to stimulate proliferation in resting T cells through an antigen non-specific mechanism. The in vivo usefulness of this T cell-T cell activation is unclear, but it may serve to amplify immune responses. T cell-T cell activation could be involved in the well-documented occurrence of multiple sclerosis (MS) exacerbations following viral infections. Excessive activation via this pathway could also be a factor in the etiology of MS. We tested the hypothesis that excessive T cell-T cell activation occurs in MS patients using in vitro proliferation assays comparing T cells from MS patients to T cells from controls. When tested as responder cells, T cells from MS patients proliferated slightly less after stimulation with previously activated cells than T cells from controls. When tested as stimulator cells, activated cells from MS patients stimulated slightly more non-specific proliferation than activated cells from controls. Neither of these differences were statistically significant We conclude that T cell proliferation in response to activated T cells is similar in MS and controls.

Long-term imatinib therapy promotes bone formation in CML patients

Blood ◽  
2008 ◽  
Vol 111 (5) ◽  
pp. 2538-2547 ◽  
Author(s):  
Stephen Fitter ◽  
Andrea L. Dewar ◽  
Panagiota Kostakis ◽  
L. Bik To ◽  
Timothy P. Hughes ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Imatinib Therapy ◽  
Term Therapy ◽  
Bone Homeostasis ◽  
Bone Biopsies ◽  
Long Term Therapy

Imatinib inhibits tyrosine kinases important in osteoclast (c-Fms) and osteoblast (platelet-derived growth factor receptor [PDGF-R], c-Abl) function, suggesting that long-term therapy may alter bone homeostasis. To investigate this question, we measured the trabecular bone volume (TBV) in iliac crest bone biopsies taken from chronic myeloid leukemia (CML) patients at diagnosis and again after 2 to 4 years of imatinib therapy. Half the patients (8 of 17) showed a substantive increase in TBV (> 2-fold), after imatinib therapy, with the TBV in the posttreatment biopsy typically surpassing the normal upper limit for the patient's age group. Imatinib-treated patients exhibited reduced serum calcium and phosphate levels with hypophosphatemia evident in 53% (9 of 17) of patients. In vitro, imatinib suppressed osteoblast proliferation and stimulated osteogenic gene expression and mineralized-matrix production by inhibiting PDGF receptor function. In PDGF-stimulated cultures, imatinib dose-dependently inhibited activation of Akt and Crk-L. Using pharmacologic inhibitors, inhibition of PI3-kinase/Akt activation promoted mineral formation, suggesting a possible molecular mechanism for the imatinib-mediated increase in TBV in vivo. Further investigation is required to determine whether the increase in TBV associated with imatinib therapy may represent a novel therapeutic avenue for the treatment of diseases that are characterized by generalized bone loss.

INFLUENCE OF CHLOROPHENOXYISOBUTYRATE (CPIB) ON THYROID PARAMETERS

1969 ◽  
Vol 60 (2) ◽  
pp. 294-302 ◽  
Author(s):  
J. Mølholm Hansen
Keyword(s):  
Free Thyroxine ◽  
Term Therapy ◽  
Low Doses ◽  
Testosterone Metabolism ◽  
Pre Treatment ◽  
Long Term Therapy ◽  
Higher Doses

ABSTRACT Chlorophenoxyisobutyrate (CPIB) added to serum in vitro increases the quantity of dialysable thyroxine. The same effect can be obtained in vivo following large doses of the preparation. After low doses, increase in serum proteinbound iodine (PBI) is observed and with higher doses this increase is not observed, probably because of the thyroxine-displacing effect. Free thyroxine increases in practically all patients investigated. In long-term treated patients the alterations in dialysable thyroxine, serum proteinbound iodine and free thyroxine are transient; pre-treatment values being regained in the course of ½–4 months. 131I uptake in the thyroid gland is influenced irregularly and transiently possibly via inhibition of the thyrotrophin production in the hypophysis. The effect of CPIB on serum cholesterol appears, in long-term therapy, to be completely independent of the effect on these thyroid parameters. This observation is also supported by the fact that the 14C-testosterone metabolism is normal in patients receiving long-term therapy.

scholarly journals CTLA-4: a negative regulator of autoimmune disease.

1996 ◽  
Vol 184 (2) ◽  
pp. 783-788 ◽  
Author(s):  
N J Karandikar ◽  
C L Vanderlugt ◽  
T L Walunas ◽  
S D Miller ◽  
J A Bluestone
Keyword(s):  
T Cells ◽  
Autoimmune Disease ◽  
Demyelinating Disease ◽  
Negative Regulator ◽  
Autoimmune Encephalomyelitis ◽  
Activated T Cells ◽  
In Vitro Proliferation ◽  
Lymph Node Cells

CTLA-4, a CD28 homologue expressed on activated T cells, binds with high affinity to the CD28 ligands, B7-1 (CD80) and B7-2 (CD86). This study was designed to examine the role of CTLA-4 in regulating autoimmune disease. Murine relapsing-remitting experimental autoimmune encephalomyelitis (R-EAE) is a demyelinating disease mediated by PLP139-151-specific CD4+ T cells in SJL/J mice. Anti-CTLA-4 mAbs (or their F(ab) fragments) enhanced in vitro proliferation and pro-inflammatory cytokine production by PLP139-151-primed lymph node cells. Addition of either reagent to in vitro activation cultures potentiated the ability of T cells to adoptively transfer disease to naive recipients. In vivo administration of anti-CTLA-4 mAb to recipients of PLP139-151-specific T cells resulted in accelerated and exacerbated disease. Finally, anti-CTLA-4 treatment of mice during disease remission resulted in the exacerbation of relapses. Collectively, these results suggest that CTLA-4 mediates the downregulation of ongoing immune responses and plays a major role in regulating autoimmunity.

Secondary myelodysplastic syndrome following long-term treatment with azathioprine in patients with multiple sclerosis

2006 ◽  
Vol 12 (3) ◽  
pp. 363-366 ◽  
Author(s):  
Norman Putzki ◽  
Sabine Knipp ◽  
T im Ramczykowski ◽  
Susanne Vago ◽  
Ulrich Germing ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Term Treatment ◽  
Immunosuppressive Drug ◽  
Term Therapy ◽  
Secondary Myelodysplastic Syndrome ◽  
Long Term Treatment ◽  
Complete Blood Counts ◽  
Long Term Therapy ◽  
Dose Dependent

Azathioprine (Aza) is a widely used immunosuppressive drug in multiple sclerosis (MS) treatment. Recently, the incidence of secondary myelodysplastic syndromes (sMDS) associated with a poor prognosis was found to be elevated in patients treated with Aza for non-malign disorders. Three hundred and seventeen MS patients were retrospectively analysed and complete blood counts were examined for those exposed to Aza. We identified one case of sMDS (cumulative dose 627 g) in a young patient and two further malignancies (cumulative doses 27 g and 54 g) in the Aza group ( n=81; 3.7%). In the non-Aza ( n=236) group, five malignancies (2.1%, P=0.419) were identified. Including our patient, four cases of sMDS after long-term Aza therapy in MS have been reported so far. Cases suggest a time- and dose-dependent risk of sMDS in long-term therapy of MS with Aza. Long-term Aza therapy needs careful monitoring.

Optimizing Immunomodulatory Therapy with Interferon Beta in Patients with Multiple Sclerosis

2010 ◽  
Vol 12 (4) ◽  
pp. 147-154 ◽  
Author(s):  
Said Masri ◽  
Andreas Blodau ◽  
Norbert Zessack ◽  
Michael Lang ◽  
Keyword(s):  
Multiple Sclerosis ◽  
Interferon Beta ◽  
Therapeutic Option ◽  
Scale Model ◽  
Term Therapy ◽  
Disability Progression ◽  
Treatment Optimization ◽  
Long Term Therapy ◽  
Immunomodulatory Therapies

Patients with multiple sclerosis (MS) may change immunomodulatory therapies if efficacy is considered inadequate or if adverse drug reactions occur. Identifying potential candidates for therapy adjustment is an important aspect of treatment optimization. This study aimed to evaluate the safety and efficacy of interferon beta-1a (IFNβ-1a), 44 μg subcutaneously (SC) three times weekly, in patients with relapsing MS following a change from another long-term therapy and to identify potential candidates for therapy adjustment. Patients were followed for 12 months. Candidates for therapy adjustment were identified using a three-scale model of treatment efficacy (relapses, disability progression, and magnetic resonance imaging). For 76.4% of patients, insufficient efficacy of the previous therapy was the main reason for changing to IFNβ-1a 44 μg. At baseline, 70.6% of patients fulfilled the criteria for recommendation for therapy adjustment; after 12 months on IFNβ-1a 44 μg, this percentage decreased to 16.6%. The incidence of adverse events (AEs) decreased between week 4 (40.6% of patients) and month 12 (12.8%). Influenza-like symptoms were the most common AE, occurring in 28.3% of patients. This study supports IFNβ-1a, 44 μg SC three times weekly, as a therapeutic option for patients in need of therapy adjustment.

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