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0568 Action of CD4+CD25+ regulatory T cells is impaired in multiple sclerosis patients
Poster Abstracts Prasad, A, Munawwix, A, Anand, K. University Science Malaysia;
Ram Manohar Lohia Hospital - New Delhi India Aim and Objective: To study the clinical features and epidemiological data o f patients diagnosed as multiple sclerosis at Hospital University Science Malaysia A tertiary level University Hospital catering to patients from whole o f East coast o f Malaysia. Results anti Discussion: Over a period of 2 years (12002-2004) we diagnosed Ten patients with Multiple Sclerosis based on the criteria of the International Panel on MS (2001). All patients in our series had Relapsing Remitting form of Multiple Sclerosis. Our data showed 92°,5 patient were females compared to overall epidemiological data worldwide which shown 2 : 1 ratio. Mean age of the patients were 30 ± 3.7 years with the youngest aged 13 and the oldest aged 60 years. Socioeconomic data revealed that the majority (70%) were in the medium and lfigh income group. Hemparesis, Paraparesis and bladder problem were the three most common presentation accounting for 42% of cases. Cerebellar involvement was least common, seen only in quarter of our patients. Clinical Optic. nerve involvement was seen in 6 patients All patients had abnormal MRI - 75 % had multiple white matter lesions, 16% had lesions in the spinal cord and only 8°,5 had cerebellar lesion. Spinal cord lesions were long involving 3-4 spinal segments consistent with other reports from S.E Asia. Evoked Potential testing revealed VEP abnormalities in 83% (Predominantly prolonged latencies) and BAER in 50%. Methylprednisolone was given in 92% of the patients in acute phase. 75% of our patients are on interferon treatment. Conclusion: Multiple Sclerosis is an under diagnosed disease in Malaysia with features which are different from the type described in Western literature. Our observations are consistent with the form described from Asia with predominant Spinal variety and less frequent optic, involvement. 0567 Role of Oxidative Stress in tile development of fatigue in patients with Multiple Sclerosis Prokopiv, M l, Vinychuk, S ~, Kopchak, 01 . 1National Medical
University, Kiev, U]craine Background: Metabolic and biochemfcal disorders play a great role in the development of multiple sclerosis (MS) symptoms. Goals: To investigate the possible role of biochemical disorders in the development of fatigue in patients with MS. Method: 49 patients with MS (122- males, 27 - females) were enrolled in the study. All the patients were demographically compared and divided into two groups: with fatigue 39 and without it 10 patients. 10 healthy individuals formed control group. Results: Patients with fatigue had more prominent disturbances of oxidative-antioxidant balance: the prevalence of primary lipid peroxidation products (LPP) (33,9 ± 5,9 mkM. 1~, p < 0,05) and secondary LPP (37,6 ± 2,6 aM. g-~ hemoglobin, p < 0,05) content over the capacity of antioxidant systems to eliminate them, proved by decreased level of atttioxidant enzyme glutattfione peroxidase (1579,4 ± 15,9 mkMg 1 hemoglobin (min 1; P < 0,05). Such disturbances were less prominent in patients without fatigue (primary LPP content was (1:1,3 ± 2,8 mkM. 11, < 0,05) and secondary LPP level was (125,7 ± 2,9 nM.(g-lhemoglobin, p<0,05). Also there were no reduction of glutattfione peroxidase level (663,6 ± 19,9 mkM (g 1 hemoglobin rain 1). The severity of fatigue increased during relapse phase of MS and was accompanied by development of the oxidative stress. The positive correlation was established between the level of oxidative stress and severity of fatigue in patients. Conclusion: Our study found the relationslfip between fatigue and oxidative-antioxidant misbalance and proved the role of oxidative stress in the development of fatigue in MS.
Tuesday, November 8, 2005
$243
0568 Action of CD4--CD25-- regulatory T cells is impaired in Multiple Sclerosis patients Putzki, N 1, Kumar, M 2, Vago, S 1, Kreuzfelder, E 2, Limmroth, V 1.
1Dept. of Neurology, University Hospital Essen, Germany; 2Institute of Immunology, University Hospital Essen, Germany Background: Multiple Sclerosis (MS) is regarded as an inflammatory demyelinating disorder including autoimmune responses to selfantigens in a genetically susceptible host. Autoaggressive processes involve T-cell activity targeting Myelin Basic Protein (MBP), a component of the myelin. CD4+ CD25+ regulatory T cells (Treg) play an important role in the control of autoimmunity by suppressing autoreactive T cells. To examine the function of Treg in MS, we compared the function of CD4+ CD25+ Treg in untreated patients (n - 16) with relapsing remitting MS and 12 age-matched healthy controls. Method: We examined lymphocyte proliferation using MBP as antigen and Pokeweed mitogen (PWM) in order to quantify the suppression activity. Highly pure CD4+ C D 2 5 - responder cells and CD4+CD25+ Treg cell populations were isolated by inmmnodensity centrifugation and inmrunomagnetic separation. Results: Stimulation with MBP and P W M led to significant proliferation of CD4+CD25 in both groups. Co-culturing of CD4+CD25+ cells with C D 4 + C D 2 5 - cells significantly reduced the MBP and P W M induced cell proliferation in controls (MBP: 51% median reduction, p - 0.007; PMW: 25% median reduction, p - 0.007). In MS patients, co-culturing did not lead to significant suppression (MBP: 12% median reduction, p -- 0.96; PWM: 7°,5 median reduction, p - 0.28). Conclusion: Results confirm previous findings that postulated a defect in regulatory T-cell function in MS. To our knowledge, this is the first time, a T-cell regulatory deficit was proven after stimulation with MBP. We propose tiffs experimental setting as a model to monitor the effects of inmmnomodulatory drugs on regulatory T-cell subsets to gain further knowledge on MS pathophysiology. 0569 Quality of life (QOL) in Multiple Sclerosis (MS) in Mexico {preliminary reporO Ramirez-Casillus, G ~, Macias-Islas, M 1, Villalpando-Gueich, M 1, Montoya, J~, Lopez-Prieto, J~, Duriez, E l, Rivera-Olmos, V 2, Lozano-Zarate, J~. 1Neurology Departament, Mexican Institute of
Social Security Maxine Mesinger MS Clinic, Multiple Sclerosis Center at The Methodist Hospital MS affects QOL importantly. QOL is a subjective individual term adjoining several components. QOL are commonly assessed by standardized surveys. We evaluate the Expanded Disability Status Scale (EDSS) by physical examination and self-reported QOL (SF-36) validated for M6xico, depression (Hamilton), fatigue (Kurpp) and Pain questionnaires in multiple sclerosis remittent recurrent (MSRR) patients and were correlate with the scores obtained by the EDSS. We recruited 220 patients from tertiary care centers living at different Mexican states of the N o r t h and Central-West regions. All the patients were diagnosed as M S R R clinically definite patients, according with Poser criteria, without relapses or steroid therapy in the last 30 days. The general profile of the group was: median age of 31 years old (16-56 range), EDSS 2.9 ± 1.5; median scores for QOL (SF-36) subscales were: 49 for physical functioning, 32 for physic, role and 62 for social functioning; all of them with significant correlation with EDSS. Hamilton, Fatigue and Pain questionnaires gave respectively: means of 11, 56 and 41, without statistical correlation. Our study showed an important decrease in the QOL of patients with MS of the north and central western regions from Mexico, compared with normal population. Social and Physical roles are the
Ram Manohar Lohia Hospital - New Delhi India Aim and Objective: To study the clinical features and epidemiological data o f patients diagnosed as multiple sclerosis at Hospital University Science Malaysia A tertiary level University Hospital catering to patients from whole o f East coast o f Malaysia. Results anti Discussion: Over a period of 2 years (12002-2004) we diagnosed Ten patients with Multiple Sclerosis based on the criteria of the International Panel on MS (2001). All patients in our series had Relapsing Remitting form of Multiple Sclerosis. Our data showed 92°,5 patient were females compared to overall epidemiological data worldwide which shown 2 : 1 ratio. Mean age of the patients were 30 ± 3.7 years with the youngest aged 13 and the oldest aged 60 years. Socioeconomic data revealed that the majority (70%) were in the medium and lfigh income group. Hemparesis, Paraparesis and bladder problem were the three most common presentation accounting for 42% of cases. Cerebellar involvement was least common, seen only in quarter of our patients. Clinical Optic. nerve involvement was seen in 6 patients All patients had abnormal MRI - 75 % had multiple white matter lesions, 16% had lesions in the spinal cord and only 8°,5 had cerebellar lesion. Spinal cord lesions were long involving 3-4 spinal segments consistent with other reports from S.E Asia. Evoked Potential testing revealed VEP abnormalities in 83% (Predominantly prolonged latencies) and BAER in 50%. Methylprednisolone was given in 92% of the patients in acute phase. 75% of our patients are on interferon treatment. Conclusion: Multiple Sclerosis is an under diagnosed disease in Malaysia with features which are different from the type described in Western literature. Our observations are consistent with the form described from Asia with predominant Spinal variety and less frequent optic, involvement. 0567 Role of Oxidative Stress in tile development of fatigue in patients with Multiple Sclerosis Prokopiv, M l, Vinychuk, S ~, Kopchak, 01 . 1National Medical
University, Kiev, U]craine Background: Metabolic and biochemfcal disorders play a great role in the development of multiple sclerosis (MS) symptoms. Goals: To investigate the possible role of biochemical disorders in the development of fatigue in patients with MS. Method: 49 patients with MS (122- males, 27 - females) were enrolled in the study. All the patients were demographically compared and divided into two groups: with fatigue 39 and without it 10 patients. 10 healthy individuals formed control group. Results: Patients with fatigue had more prominent disturbances of oxidative-antioxidant balance: the prevalence of primary lipid peroxidation products (LPP) (33,9 ± 5,9 mkM. 1~, p < 0,05) and secondary LPP (37,6 ± 2,6 aM. g-~ hemoglobin, p < 0,05) content over the capacity of antioxidant systems to eliminate them, proved by decreased level of atttioxidant enzyme glutattfione peroxidase (1579,4 ± 15,9 mkMg 1 hemoglobin (min 1; P < 0,05). Such disturbances were less prominent in patients without fatigue (primary LPP content was (1:1,3 ± 2,8 mkM. 11, < 0,05) and secondary LPP level was (125,7 ± 2,9 nM.(g-lhemoglobin, p<0,05). Also there were no reduction of glutattfione peroxidase level (663,6 ± 19,9 mkM (g 1 hemoglobin rain 1). The severity of fatigue increased during relapse phase of MS and was accompanied by development of the oxidative stress. The positive correlation was established between the level of oxidative stress and severity of fatigue in patients. Conclusion: Our study found the relationslfip between fatigue and oxidative-antioxidant misbalance and proved the role of oxidative stress in the development of fatigue in MS.
Tuesday, November 8, 2005
$243
0568 Action of CD4--CD25-- regulatory T cells is impaired in Multiple Sclerosis patients Putzki, N 1, Kumar, M 2, Vago, S 1, Kreuzfelder, E 2, Limmroth, V 1.
1Dept. of Neurology, University Hospital Essen, Germany; 2Institute of Immunology, University Hospital Essen, Germany Background: Multiple Sclerosis (MS) is regarded as an inflammatory demyelinating disorder including autoimmune responses to selfantigens in a genetically susceptible host. Autoaggressive processes involve T-cell activity targeting Myelin Basic Protein (MBP), a component of the myelin. CD4+ CD25+ regulatory T cells (Treg) play an important role in the control of autoimmunity by suppressing autoreactive T cells. To examine the function of Treg in MS, we compared the function of CD4+ CD25+ Treg in untreated patients (n - 16) with relapsing remitting MS and 12 age-matched healthy controls. Method: We examined lymphocyte proliferation using MBP as antigen and Pokeweed mitogen (PWM) in order to quantify the suppression activity. Highly pure CD4+ C D 2 5 - responder cells and CD4+CD25+ Treg cell populations were isolated by inmmnodensity centrifugation and inmrunomagnetic separation. Results: Stimulation with MBP and P W M led to significant proliferation of CD4+CD25 in both groups. Co-culturing of CD4+CD25+ cells with C D 4 + C D 2 5 - cells significantly reduced the MBP and P W M induced cell proliferation in controls (MBP: 51% median reduction, p - 0.007; PMW: 25% median reduction, p - 0.007). In MS patients, co-culturing did not lead to significant suppression (MBP: 12% median reduction, p -- 0.96; PWM: 7°,5 median reduction, p - 0.28). Conclusion: Results confirm previous findings that postulated a defect in regulatory T-cell function in MS. To our knowledge, this is the first time, a T-cell regulatory deficit was proven after stimulation with MBP. We propose tiffs experimental setting as a model to monitor the effects of inmmnomodulatory drugs on regulatory T-cell subsets to gain further knowledge on MS pathophysiology. 0569 Quality of life (QOL) in Multiple Sclerosis (MS) in Mexico {preliminary reporO Ramirez-Casillus, G ~, Macias-Islas, M 1, Villalpando-Gueich, M 1, Montoya, J~, Lopez-Prieto, J~, Duriez, E l, Rivera-Olmos, V 2, Lozano-Zarate, J~. 1Neurology Departament, Mexican Institute of
Social Security Maxine Mesinger MS Clinic, Multiple Sclerosis Center at The Methodist Hospital MS affects QOL importantly. QOL is a subjective individual term adjoining several components. QOL are commonly assessed by standardized surveys. We evaluate the Expanded Disability Status Scale (EDSS) by physical examination and self-reported QOL (SF-36) validated for M6xico, depression (Hamilton), fatigue (Kurpp) and Pain questionnaires in multiple sclerosis remittent recurrent (MSRR) patients and were correlate with the scores obtained by the EDSS. We recruited 220 patients from tertiary care centers living at different Mexican states of the N o r t h and Central-West regions. All the patients were diagnosed as M S R R clinically definite patients, according with Poser criteria, without relapses or steroid therapy in the last 30 days. The general profile of the group was: median age of 31 years old (16-56 range), EDSS 2.9 ± 1.5; median scores for QOL (SF-36) subscales were: 49 for physical functioning, 32 for physic, role and 62 for social functioning; all of them with significant correlation with EDSS. Hamilton, Fatigue and Pain questionnaires gave respectively: means of 11, 56 and 41, without statistical correlation. Our study showed an important decrease in the QOL of patients with MS of the north and central western regions from Mexico, compared with normal population. Social and Physical roles are the