ABSTRACT
The objectives were to study the expression of very late antigen (VLA)-4, melanoma cell adhesion molecule-1 (MCAM-1) and activated leukocyte cell adhesion molecule (ALCAM) on CD4+ T cells during natalizumab treatment and to investigate the association with disease activity. We find that subgroups of autoreactive T cells are retained in peripheral blood, in particular MOG-reactive CD4+ T cells expressing MCAM-1. The expression of MCAM-1 or ALCAM on CD4+ T cells was, however, not clearly associated with disease activity (clinical or MRI) during natalizumab treatment. We confirm upregulation of MCAM-1 on CD4+ T cells during natalizumab treatment while VLA-4 is downregulated.
Subject(s)
CD4-Positive T-Lymphocytes/metabolism , Immunologic Factors/administration & dosage , Multiple Sclerosis/blood , Multiple Sclerosis/drug therapy , Natalizumab/administration & dosage , Adult , Aged , CD146 Antigen/biosynthesis , CD146 Antigen/blood , CD4-Positive T-Lymphocytes/drug effects , Cohort Studies , Female , Gene Expression , Humans , Infusions, Intravenous , Male , Middle Aged , Prospective Studies , Young AdultABSTRACT
BACKGROUND: Natalizumab reduces disease activity in multiple sclerosis (MS). Natalizumab binds to the very late antigen-4 and inhibits vascular cell adhesion molecule-1 (VCAM-1)-mediated transmigration of immune cells across the blood-brain-barrier. This is associated with decreased serum concentrations of soluble (s)VCAM-1 and an altered composition of immune cell-subsets in the blood. OBJECTIVE: We aimed to examine if sVCAM-1 serum concentrations and whole blood mRNA expression levels of immune activation biomarkers is associated with disease activity in natalizumab-treated MS-patients. METHODS: sVCAM-1 serum concentrations and whole blood mRNA expression were measured in blood samples from untreated RRMS-patients and from two independent groups of natalizumab-treated patients. RESULTS: sVCAM-1 serum concentrations and whole blood expression of HLX1 and IL1B mRNA were lower, whereas expression of EBI3 mRNA was higher in natalizumab-treated MS-patients. Five genes were differentially expressed in clinically unstable natalizumab-treated MS-patients in the discovery but not in the validation group. CONCLUSION: Decreased serum concentrations of sVCAM-1 and altered whole blood mRNA expression levels of a panel of immunomarkers, associated with natalizumab-treatment, are not sensitive markers of MS disease activity. However, decreased expression of pro-inflammatory HLX1 and IL1B and increased expression of immunoregulatory EBI3 may indicate a less pathogenic immune activation status in natalizumab-treated MS.
Subject(s)
Immunologic Factors/therapeutic use , Multiple Sclerosis/blood , Multiple Sclerosis/drug therapy , Natalizumab/therapeutic use , RNA, Messenger/blood , Vascular Cell Adhesion Molecule-1/blood , Adult , Biomarkers, Pharmacological/blood , Cohort Studies , Female , Glucocorticoids/therapeutic use , Homeodomain Proteins/blood , Humans , Interleukin-1beta/blood , Interleukins/blood , Male , Middle Aged , Minor Histocompatibility Antigens/blood , Multiple Sclerosis/immunology , Time Factors , Transcription Factors/bloodABSTRACT
Recent work has showed high positive oxidation-reduction potential (Eh) values in fresh fish flesh, whereas strongly reducing conditions exist in fish viscera and spoiled fish flesh. The present study has demonstrated that this difference in measured Eh does not significantly influence growth and toxin production by Cl. botulinum type E. In comparison, storage temperature and the spore load in fish markedly influence toxin production. The public health significance of rapid toxin formation and high toxin titers demonstrated in ungutted fish is pointed out.
