Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0848771 (neurological disability)
 928 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Depression is a common problem in multiple sclerosis (MS) and affects about 50% of MS patients. Since a dysregulation of cytokine levels has been implicated in the pathogenesis of MS and alterations in cytokine serum levels have been found in depressive illness, we examined the relationship between depressive symptoms, cytokine mRNA expression levels of Th1-type and Th2-type cytokines and neurological disability among early diagnosed MS patients in a prospective study. Sixteen patients with clinically or laboratory supported MS were assessed using the Beck Depression Inventory (BDI) and the Kurtzke Expanded Disability Status Scale (EDSS). Cytokine mRNA in whole blood was serially determined by a new quantitative polymerase chain reaction (PCR) method. BDI sum scores (2,9 fold) and the expression levels of tumor necrosis factor-alpha (TNF-alpha; 4 fold), interferon-gamma (IFN-gamma; 4,6 fold) and interleukin-10 (IL-10; 6,1 fold) mRNA were increased in MS patients during an acute attack compared to age and sex matched healthy controls. We detected a significant positive correlation between TNF-alpha (r=0.55) and interferon-gamma (r=0.54) mRNA expression and the BDI sum scores during an acute attack in MS patients. At follow-up after 3-6 months, only TNF-alpha mRNA expression was correlated with BDI sum scores (r=0.62 resp. r=0.31). No correlation of the BDI sum scores with Th2-type cytokine mRNA expression for interleukin-4 (IL-4) and interleukin-10 (IL-10) or with the extent of neurological disability was observed. The possible contribution of Th1-type cytokines to the development of depression in MS is discussed.
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PMID:Expression of tumor necrosis factor-alpha and interferon-gamma mRNA in blood cells correlates with depression scores during an acute attack in patients with multiple sclerosis. 1208 60

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system in which axonal damage and degeneration contribute significantly to the progressive irreversible neurological disability. Similar to pathogenic myelin autoimmunity, autoimmune responses to neuronal antigens may contribute to axonal damage and irreversible disability in MS. Auto-antibodies to the axonal cytoskeletal protein neurofilament light (NF-L) are associated with cerebral atrophy in MS and we have recently reported that NF-L autoimmunity is pathogenic in mice. However, the T-cell response to NF-L in MS patients has not been examined. Here, we identify and characterize T-cell proliferative responses to NF-L as compared with myelin oligodendrocyte glycoprotein (MOG) in MS patients and healthy controls. Using a carboxyfluorescein succinimidyl ester dilution assay, we show that while responses to MOG are dominated by CD3(+)CD4(+) T cells, responses to NF-L were observed in both CD3(+)CD4(+) and CD3(+)CD8(+) T-cell populations. Both MOG- and NF-L-reactive cells expressed CD45RO(+), indicative of a memory phenotype. Moreover, in contrast to MOG stimulation which predominantly induced IFN-gamma, both T(h)1- and T(h)2-type T-cell responses to NF-L were observed as indicated by the induction of IFN-gamma, tumor necrosis factor-alpha as well as IL-4. The finding of T-cell responses to NF-L in MS patients may reflect transient activation of pathogenic potential but their presence also in healthy controls indicates that these cells are part of the normal immune repertoire.
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PMID:T-cell responses to neurofilament light protein are part of the normal immune repertoire. 1924 89