Intrathecal antibody production is a hallmark of multiple sclerosis and humoral immunity thought to play an important role in the inflammatory response development demyelinated lesions. The presence lymphoid follicle-like structures cerebral meninges some patients indicates that B-cell maturation can be sustained locally within CNS contribute establishment compartmentalized immune response. In this study we examined distribution ectopic follicles cases with primary secondary progressive...

Multiple sclerosis (MS) is characterized by synthesis of oligoclonal immunoglobulins and the presence B‐cell clonal expansions in central nervous system (CNS). Because ectopic lymphoid tissue generated at sites chronic inflammation thought to be important sustaining immunopathological processes, we have investigated whether structures resembling follicles could identified CNS MS patients. Sections from post‐mortem brains spinal cords were screened using immunohistochemistry for CD20 +...

Meningeal inflammation in the form of ectopic lymphoid-like structures has been suggested to play a prominent role development cerebral cortical grey matter pathology multiple sclerosis. The aim this study was analyse incidence and distribution B cell follicle-like an extensive collection cases with secondary progressive sclerosis wide age range determine their relationship diffuse meningeal inflammation, white perivascular infiltrates microglial activation. One hundred twenty three were...

Epstein-Barr virus (EBV), a ubiquitous B-lymphotropic herpesvirus, has been associated with multiple sclerosis (MS), an inflammatory disease of the central nervous system (CNS), but direct proof its involvement in is still missing. To test idea that MS might result from perturbed EBV infection CNS, we investigated expression markers postmortem brain tissue cases different clinical courses. Contrary to previous studies, found evidence substantial proportion brain-infiltrating B cells and...

Prominent inflammation with formation of ectopic B-cell follicle-like structures in the meninges secondary progressive multiple sclerosis (MS) (SPMS) is associated extensive cortical pathology and an exacerbated disease course. Our objective was to evaluate cellular substrates damage understand role meningeal MS pathology.Using >600 tissue blocks from 37 cases SPMS 14 non-neurological controls, we carried out a detailed quantitative analysis atrophy layer-specific changes cell populations...

We report that B cell–activating factor of the tumor necrosis (TNF) family (BAFF) is expressed in normal human brain at ∼10% lymphatic tissues (tonsils and adenoids) produced by astrocytes. BAFF was regularly detected enzyme-linked immunosorbent assay tissue lysates spinal fluid, astrocytes double fluorescence microscopy. Cultured secreted functionally active after stimulation with interferon-γ TNF-α via a furin-like protease-dependent pathway. secretion per cell manifold higher activated...

To identify differentially expressed genes in multiple sclerosis, microarrays were used a stringent experimental setting—leukapheresis from disease-discordant monozygotic twins and gene expression profiling CD4+ CD8+ T-cell subsets. Disease-related differences emerged only the subset. The five identified included killer cell lectin-like receptor subfamily B, member 1, also known as natural protein 1a/CD161, presented by International Multiple Sclerosis Genetics Consortium one of non-MHC...

In multiple sclerosis (MS), dendritic cells (DCs) recruited to the central nervous system (CNS) are thought be involved in regulation of autoimmune responses directed against myelin antigens. To better understand role DCs CNS inflammation, we performed a detailed immunohistochemical analysis DC maturation markers and relationship CNS-infiltrating T autopsy brain tissue patients with MS. We also investigated presence containing debris MS lesions. Myeloid subsets were identified using...

It has long been known that multiple sclerosis (MS) is associated with an increased Epstein-Barr virus (EBV) seroprevalence and high immune reactivity to EBV infectious mononucleosis increases MS risk. This evidence led postulate infection plays a role in etiopathogenesis, although the mechanisms are debated. study was designed assess prevalence magnitude of CD8+ T-cell responses latent (EBNA-3A, LMP-2A) lytic (BZLF-1, BMLF-1) antigens relapsing-remitting patients (n = 113) healthy donors...

A cardinal feature of multiple sclerosis (MS) is the persistent intrathecal synthesis antibodies. Our previous finding that a large fraction B cells infiltrating MS brain are infected with Epstein-Barr virus (EBV) raises possibility this virus, because its ability to establish latent infection in and interfere their differentiation, contributes B-cell dysregulation MS. The aim study was gain further insight into EBV latency programs relationship activation brain. Immunohistochemical analysis...

Gray matter lesions are thought to play a key role in the progression of disability and cognitive impairment multiple sclerosis (MS) patients, but whether gray damage is caused by inflammation or secondary axon loss white matter, both, not clear. In an analysis postmortem brain samples from 44 cases progressive MS, 26 were characterized menin-geal with ectopic B-cell follicles prominent pathology; subpial cortical containing dense peri-vascular lymphocytic infiltrates present 11 these cases....

Rheumatoid arthritis (RA) is associated with an increased Epstein-Barr virus (EBV) blood DNA load, a robust immune response to EBV and cross-reactive circulating antibodies viral self-antigens. However, the role of in RA pathogenesis remains elusive. Here, we investigated relationship between synovial infection, ectopic lymphoid structures (ELS) immunity citrullinated self proteins.Latent lytic infection was 43 tissues characterised for presence/absence ELS 11 control osteoarthritis synovia...

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus strongly associated with multiple sclerosis (MS), chronic inflammatory disease of the central nervous system (CNS). However, mechanisms linking EBV infection to MS pathology are uncertain. Neuropathological and immunological studies suggest that persistent in CNS can stimulate CD8 T-cell response aimed at clearing but inadvertently causing injury. Inasmuch as situ demonstration EBV-specific T cells their effector function missing, we...

As a result of their close association with the blood-brain barrier, astrocytes play an important role in regulating homing different leukocyte subsets to inflamed central nervous system (CNS). In this study, we investigated whether human produce chemokines that promote migration myeloid dendritic cells (DCs). By reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay, show cultured stimulated interleukin-1β tumor necrosis factor CCL2, CCL3, CCL4, CCL5, CCL20,...

Abstract Dendritic cells (DCs) are thought to play a key role in driving the immunopathogenic response underlying chronic inflammatory arthritis. In this study, we have examined presence and phenotype of plasmacytoid DCs (pDCs) synovial fluids (SF) patients with rheumatoid arthritis (RA), psoriatic (PA), osteoarthritis (OA) determined chemotactic properties SF from these toward pDCs. Flow cytometry analysis showed that percentage pDCs, identified as population Lin−CD123++ cells, is 4- 5-fold...

The simultaneous presence of dendritic, T‐ and B‐cells in the central nervous system (CNS) mice with experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis, suggests that interactions among these cell types might be instrumental local induction maintenance reactions. In this study, we explored possibility such aberrant leukocyte recruitment CNS could sustained by “lymphoid” chemokines which orchestrate dendritic lymphocyte homing to lymphoid organs. Transcripts CCL19...

Abstract To gain insights into the role of purinergic receptors in oligodendrocyte development, we characterized expression and functional activity P2 cultured rat progenitors investigated effects ATP its breakdown products on migration proliferation this immature glial cell population. Using Western blot analysis, show that express several P2X (P2X 1,2,3,4,7 ) P2Y (P2Y 1,2,4 receptors. Intracellular Ca 2+ recording by Fura‐2 video imaging allowed to determine rank potency order agonists...

Abstract Objective Increasing evidence supports a link between Epstein‐Barr virus (EBV), ubiquitous B‐lymphotropic human herpesvirus, and common B‐cell–related autoimmune diseases. We sought of EBV infection in thymuses from patients with myasthenia gravis (MG), an disease characterized by intrathymic B‐cell activation. Methods Seventeen MG (6 follicular hyperplastic, 6 diffuse 5 involuted) control were analyzed using situ hybridization for EBV‐encoded small RNAs (EBERs),...

The roles of plasmacytoid dendritic cells (pDCs) and their response to interferon (IFN)-β therapy in multiple sclerosis (MS) patients are poorly understood. We identified pDC accumulation white matter lesions leptomeninges MS brains abundant expression the Type I IFN-induced protein MxA, mainly perivascular CD3+ lymphocytes lesions, indicating IFN production by activated pDCs. chemoattractant chemerin was detected intralesional cerebrovascular endothelial cells, receptor expressed on...

It is debated whether multiple sclerosis (MS) might result from an immunopathological response toward active Epstein-Barr virus (EBV) infection brought into the central nervous system (CNS) by immigrating B cells. Based on this model, a relationship should exist between local immune milieu and EBV status in MS brain. To test hypothesis, we analyzed expression of viral cellular genes brain-infiltrating cells.Twenty-three postmortem snap-frozen brain tissue blocks 11 patients with progressive...

The presence of EBV infected B cells in postmortem multiple sclerosis (MS) brain tissue suggests immune evasion strategies. Using immunohistochemical techniques we analysed the expression checkpoint molecule PD-L1 and its receptor PD-1 MS brains containing cell-enriched perivascular infiltrates meningeal follicles, a major reservoir. immunoreactivities were restricted to CNS-infiltrating cells. was expressed on cells, including while many CD8+ T EBV-specific T-cells, fewer CD4+ PD-L1+ close...