Journal of neuroimmunology
-
Immune cells often express various nicotinic ACh receptor (nAChR) subtypes, including α7 nAChRs, as well as mRNA encoding secreted lymphocyte antigen-6/urokinase-type plasminogen activator receptor-related peptide (SLURP)-1, an endogenous α7 nAChR allosteric ligand. We detected SLURP-1 immunoreactivity in CD205(+) dendritic cells (DCs) residing in human tonsils. Phytohemagglutinin (PHA, 10 μg/ml), a T cell activator, attenuated cell proliferation and increased the ACh content of MOLT-3 human leukemic T cells compared with the vehicle control. ⋯ Recombinant (r)SLURP-1 (0.5 μg/ml) attenuated peripheral blood mononuclear cell proliferation and increased ChAT gene expression and the ACh content in MOLT-3 cells compared with the control, all of which were abolished by MLA. This suggests SLURP-1 activates cholinergic transmission by potentiating ACh synthesis and its action at α7 nAChRs, thereby facilitating functional development of T cells. These findings support the notion that SLURP-1 acts as a key modulator of immune responses.
-
Diagnosis of IgG4-Related Hypertrophic Pachymeningitis (IgG4-HP) relies on meningeal biopsies, because cerebrospinal fluid (CSF) diagnostic biomarkers are lacking. Here, we determined whether IgG4 intrathecal production could distinguish IgG4-HP from other disorders presenting with HP (OHP). ⋯ An IgG4Loc cut-off of 0.47 identified 100% of IgG4-HP and no cases of OHP. Our results support CSF IgG4 quantification and IgG4 Indices as alternatives to meningeal biopsy for the diagnosis of IgG4-HP when this procedure is contraindicated or uninformative.
-
Using a panel of seven brain cell-specific biomarkers in cerebrospinal fluid (CSF), pediatric opsoclonus-myoclonus syndrome (OMS) (n=234) was compared to pediatric non-inflammatory neurological controls (n=84) and other inflammatory neurological disorders (OIND) (n=44). Only CSF NFL was elevated in untreated OMS versus controls (+83%). ⋯ On combination treatment with front-loaded ACTH, IVIg, rituximab, median CSF NFL decreased by 60% to control levels. These biochemical data suggest neuronal/axonal injury in some children with OMS without indicators of astrogliosis, and reduction on sufficient immunotherapy.
-
Teriflunomide is an inhibitor of dihydro-orotate dehydrogenase (DHODH), and is hypothesized to ameliorate multiple sclerosis by reducing proliferation of stimulated lymphocytes. We investigated teriflunomide's effects on proliferation, activation, survival, and function of stimulated human peripheral blood mononuclear cell subsets in vitro. ⋯ Teriflunomide significantly decreased release of several pro-inflammatory cytokines from activated monocytes in a DHODH-independent fashion. In conclusion, teriflunomide acts on multiple immune cell types and processes via DHODH-dependent and independent mechanisms.
-
Multicenter Study
Interactions of serum cholesterol with anti-herpesvirus responses affect disease progression in clinically isolated syndromes.
To investigate whether anti-herpesvirus antibodies are associated with serum cholesterol profiles in clinically isolated syndromes (CIS). ⋯ Our results indicate that higher levels of anti-EBV EBNA-1 antibodies are associated with higher LDL-C and TC levels. Anti-CMV positive individuals have greater disease progression in the presence of higher HDL-C levels. Individuals with higher levels of anti-EBV VCA antibodies have greater progression on MRI measures in the presence of higher LDL-C.