ABSTRACT
BACKGROUND: The pathophysiology of multiple sclerosis (MS)-associated fatigue is poorly understood. Immunological mechanisms may play a role. Alterations in immunological profile indicate a chronic immune activation in MS patients with fatigue. T-regulatory (Treg) cells seem to play a key role in coordinating autoimmune mechanisms in MS. This is the first study investigating the relationship between Treg cell function and fatigue in MS patients. METHODS: In this cross-sectional in vitro, ex vivo study, we isolated peripheral blood mononuclear cells (PBMCs) from 20 MS patients with fatigue, determined lymphocyte subsets by flow cytometry and suppressive function of Treg cells in PBMC cultures with antigen stimulation. Forkhead box protein 3 expression was evaluated by PCR. Results were compared with 20 MS patients without fatigue and with 19 healthy controls. RESULTS: Leukocytes and lymphocyte subsets including Treg cell frequency did not differ in patients with and without fatigue. Co-culturing of Treg cells with CD4+CD25- cells did not lead to a significant suppression of myelin basic protein- and pokeweed mitogen-induced proliferation in MS patients in contrast to healthy controls. There were no statistical differences between MS patients with and without fatigue regarding this suppression activity. CONCLUSIONS: Fatigue seems not to be associated with impaired function of Treg cells in untreated MS patients.
Subject(s)
Fatigue/physiopathology , Leukocytes, Mononuclear/physiology , Multiple Sclerosis/physiopathology , Adult , CD4-Positive T-Lymphocytes/metabolism , CD4-Positive T-Lymphocytes/physiology , Cell Count , Cell Proliferation , Cells, Cultured , Fatigue/immunology , Fatigue/metabolism , Female , Flow Cytometry , Forkhead Transcription Factors/genetics , Forkhead Transcription Factors/metabolism , Humans , Leukocytes, Mononuclear/metabolism , Male , Multiple Sclerosis/immunology , Multiple Sclerosis/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Severity of Illness Index , Statistics, NonparametricABSTRACT
Fatigue is one of the most frequent and most disabling symptoms in multiple sclerosis (MS). We investigated the possible association of the MS-related fatigue syndrome with the available disease-modifying therapies and the main disease characteristics in a cross-sectional study on 320 consecutive patients. The prevalence of severe fatigue (Fatigue Severity Scale score > or =5) was 50%. In a multivariate regression model controlling for age, disease subtype, duration and disability we did not find a significant association between the use of immunosuppressive or immunomodulatory drugs compared to no treatment (OR = 1.34, p = 0.38 for immunosuppressants; OR = 0.95, p = 0.85 for immune-modulating agents). Although all used disease-modifying agents successfully reduce disease activity and inflammation, they do not appear to exhibit a significant effect on MS-related fatigue.
Subject(s)
Fatigue/epidemiology , Fatigue/etiology , Multiple Sclerosis/complications , Adult , Chi-Square Distribution , Disability Evaluation , Disease Progression , Female , Humans , Immunologic Factors/therapeutic use , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Multiple Sclerosis/therapy , Odds Ratio , Prevalence , Retrospective Studies , Risk Factors , Severity of Illness IndexABSTRACT
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.
