Multiple sclerosis (MS) is an autoimmune disease. The etiology and pathogenesis of MS remain unclear. At present, there are substantial evidences to support the hypothesis that genetics plays a crucial role. The people who have genetic predisposing genes easily develop immune-mediated disorder, probably in conjunction with environmental factors. The aim of this review is to describe recent observations regarding the immunologic pathogenesis of MS.
Animals ; Autoantibodies ; immunology ; Humans ; Models, Biological ; Multiple Sclerosis ; etiology ; immunology ; pathology ; Myelin Basic Protein ; metabolism

To date, efforts to treat autoimmune diseases have primarily focused on the disease symptoms rather than on the cause of the disease. In large part, this is attributed to not knowing the responsible auto-antigens (auto-Ags) for driving the self-reactivity coupled with the poor success of treating autoimmune diseases using oral tolerance methods. Nonetheless, if tolerogenic approaches or methods that stimulate regulatory T (Treg) cells can be devised, these could subdue autoimmune diseases. To forward such efforts, our approach with colonization factor antigen I (CFA/I) fimbriae is to establish bystander immunity to ultimately drive the development of auto-Ag-specific Treg cells. Using an attenuated Salmonella vaccine expressing CFA/I fimbriae, fimbriae-specific Treg cells were induced without compromising the vaccine's capacity to protect against travelers' diarrhea or salmonellosis. By adapting the vaccine's anti-inflammatory properties, it was found that it could also dampen experimental inflammatory diseases resembling multiple sclerosis (MS) and rheumatoid arthritis. Because of this bystander effect, disease-specific Treg cells are eventually induced to resolve disease. Interestingly, this same vaccine could elicit the required Treg cell subset for each disease. For MS-like disease, conventional CD25+ Treg cells are stimulated, but for arthritis CD39+ Treg cells are induced instead. This review article will examine the potential of treating autoimmune diseases without having previous knowledge of the auto-Ag using an innocuous antigen to stimulate Treg cells via the production of transforming growth factor-beta and interleukin-10.
Animals ; Antigens, Bacterial/*immunology ; Arthritis, Rheumatoid/immunology/prevention & control ; Autoantigens/*immunology ; Fimbriae Proteins/*immunology ; Humans ; Multiple Sclerosis/immunology/prevention & control ; Salmonella/*immunology ; T-Lymphocytes, Regulatory/*immunology ; *Vaccination

BACKGROUNDWhether antibody to myelin oligodendrocyte glycoprotein (MOG) can be a diagnostic marker for multiple sclerosis (MS) is still controversial. Recent studies suggested that serum specific anti-MOG epitope antibody might be an MS specific marker. However, these studies did not include neuromyelitis optica (NMO) which might be proven to also have anti-MOG antibody. Hence, the present study was undertaken to investigate the clinical value of serum antibodies to 25 MOG epitopes in conventional MS (CMS) and NMO.

METHODSSerum anti-MOG epitope IgG was detected in 61 CMS patients, 54 NMO patients, and 77 healthy controls, using enzyme-linked immunosorbent assay (ELISA).

RESULTSAnti-MOG(27-38) IgG levels in both CMS and NMO patients were significantly higher than that in healthy controls (optical density (OD): 0.64 ± 0.38, 0.48 ± 0.23 vs. 0.19 ± 0.09; P = 0.000). CMS and NMO patients in relapse stage had significantly higher anti-MOG(27-38) IgG level than patients in remission stage (OD: 0.55 ± 0.14 vs. 0.24 ± 0.09, P = 0.027).

CONCLUSIONAlthough serum anti-MOG epitope IgG could not differentiate MS from NMO, it may be a useful marker for monitoring disease activity.

Adult ; Antibodies ; blood ; immunology ; Epitopes ; immunology ; Female ; Humans ; Male ; Middle Aged ; Multiple Sclerosis ; blood ; immunology ; Myelin-Oligodendrocyte Glycoprotein ; immunology ; Neuromyelitis Optica ; blood ; immunology

OBJECTIVETo study the relation between the recent active infection with Epstein-Barr virus, cytomegalovirus,herpes simplex virus-1, coxsackievirus B I-IV and the relapse of relapsing-remitting multiple sclerosis (RR MS).

METHODSUsing ELISA method, IgM antibodies to Epstein-Barr virus, cytomegalovirus, herpes simplex virus-1, coxsackievirus BI-IV in the plasma from 34 RR MS patients and 200 normal controls were detected. The rates of recent active infection with the above mentioned viruses of the patients and controls were compared.For patients group,comparison was also made between the clinical data of recent active infected patients and patients without recent active infection.

RESULTSThere was no statistically significant difference in positive rates of positive rates of IgM antibodies against Epstein-Barr virus, cytomegalovirus, herpes simplex virus-1 and coxsackievirus BI, II, III or VI between the two groups. While there was statistically significant difference in positive rates of IgM antibodies to coxsackievirus B VI and V in the RR MS patients and those in the controls (being 3/34 and 0/200 P < 0.05; 2/34 and 0/200 P < 0.05, respectively). In the patient group, when patients who had active infection with any of the viruses were compared with those who had no active infection, no significant difference between them was found in terms of age, course, frequency, body temperature on admission, differential leukocyte count (neutrophilic granulocyte, lymphocyte and monocytes), use of glucocorticoids, and EDSS point value.

CONCLUSIONSThere is a high rate of recent active infection with coxsackievirus B VI and V in RR MS patients at relapsing stage. While the recent virus active infection is unrelated to the severity of the symptoms.

Antibodies, Viral ; immunology ; Antigens, Viral ; immunology ; Coxsackievirus Infections ; immunology ; Cytomegalovirus Infections ; immunology ; Enterovirus B, Human ; immunology ; Enterovirus Infections ; immunology ; Epstein-Barr Virus Infections ; immunology ; Herpes Simplex ; immunology ; Herpesvirus 1, Human ; immunology ; Herpesvirus 4, Human ; immunology ; Humans ; Multiple Sclerosis ; immunology ; Multiple Sclerosis, Relapsing-Remitting ; immunology ; Recurrence ; Simplexvirus ; immunology

OBJECTIVETo assess the seroprevalence and diagnostic value of aquaporin-4 antibody (AQP4-Ab) in patients with inflammatory central nervous system demyelinating diseases.

METHODSSeventy-two patients with neuromyelitis optica (NMO), 68 with multiple sclerosis (MS), 4 with optic neuritis (ON), and 41 with transverse myelitis (TM) were included in this study. The TM group comprised 19 patients with non-longitudinally extensive transverse myelitis (nLETM), 14 with monophasic longitudinally extensive transverse myelitis (mLETM), and 8 with recurrent longitudinally extensive transverse myelitis (rLETM). The serum levels of AQP4-Ab was detected by indirect immunofluorence assay in these patients.

RESULTSAQP4-Ab was detected in 72.2% (52/72) patients with NMO, 5.9% (4/68) patients with MS, 25.0% (1/4) patients with ON, and 17.1% (7/41) patients with TM, showing a significant difference in the positivity between NMO and MS groups (P<0.01). AQP4-Ab seropositivity rate was 5.3% (1/19) in nLETM patients, 62.5% (5/8) in rLETM patients and 7.1% (1/14) in mLETM patients, significantly higher in rLETM than in nLETM (P<0.01) and mLETM groups (P<0.05), but no statistical difference was found between rLETM and NMO groups.

CONCLUSIONSA high seroprevalence of AQP4-Ab is observed in patients with NMO and rLETM, which support the hypothesis that NMO and rLETM belong to NMO spectrum disorders. AQP4-Ab can serve as a useful index for diagnosing NMO and differential diagnosis from MS. More attention and effective immunosuppressive treatments should be given to patients positive for AQP4-Ab.

Aquaporin 4 ; immunology ; Autoantibodies ; blood ; Demyelinating Autoimmune Diseases, CNS ; diagnosis ; immunology ; Female ; Humans ; Male ; Multiple Sclerosis ; diagnosis ; immunology ; Neuromyelitis Optica ; diagnosis ; immunology ; Seroepidemiologic Studies

A large body of evidence demonstrates that dendritic cells (DC) play a pivotal role in the control of immunity by priming and tolerizing T cells. In multiple sclerosis (MS), autoreactive T cells are proposed to play a pathogenic role by secreting pro-inflammatory cytokines, but comparison studies on the effects of immature and mature dendritic cells on the cytokines profile of antigen-specific T cell lines are lacking. To evaluate the actions of dendritic cell maturation on T cell polarization, the effects of immature and mature dendritic cells derived from MS patients on in vitro proliferative responses, and cytokine production by glatiramer acetate (GA)- specific T cell lines (TCL) derived from MS patients were analyzed. The results demonstrated that it is easy to derive GA-specific TCL from MS patients with high specificity; lipopolysaccharide can efficiently induce DC maturation within 24 hours at a concentration of 5 micro g/ml; mature DC showed higher co-stimulatory capacity of GA-specific TCLs than immature DC. GA-specific TCLs produce dominantly IL-2, IL-4, IFN-gamma and IL-10, but low levels of IL-6. In contrast to immature DC, mature DC enhanced capacity to induce IL-6 and IL-10 secretion, but down-regulate IL-2, IL-4 and IFN-gamma production by GA- specific TCLs. It is concluded that DC maturation status modulating proliferation of TCL and production of cytokines may represent another focus for the study on both immuno-pathogenesis and immunotherapeutic interventions in MS.
Adult ; Cell Line ; Cytokines ; biosynthesis ; Dendritic Cells ; physiology ; Female ; Glatiramer Acetate ; Humans ; Lymphocyte Activation ; Male ; Middle Aged ; Multiple Sclerosis ; immunology ; Peptides ; immunology ; T-Lymphocytes ; immunology

OBJECTIVEMultiple sclerosis is a demyelinating disease frequently showing a relapsing-remitting disease course. Clinical manifestations of 25 inpatients with MS were summarized and analyzed so that the clinical features and therapeutic approaches to childhood multiple sclerosis (MS) were investigated in order to improve its diagnosis and management.

METHODSClinical features and information during following-up of 25 cases with MS from June 1993 to May 2006 were collected and analyzed.

RESULTSAmong the 25 cases, 16 were female and the F:M ratio was 1.78:1. The relapsing-remitting type was seen in 21 cases, the secondary progressive MS in 3 cases and the classification was impossible in one case. The mean age of onset was 6.7 years (2-12) with various initial symptoms including visual loss (11 cases), cortical symptoms (8 cases with seizures, consciousness disturbance, aphasia and apraxia, etc.), myeleterosis (3 cases), symptoms of brainstem (2 cases) and cerebellar ataxia (1 case). Fever was present in 10 cases at the onset. Nine cases were monosymptomatic, while the other 16 had multiple symptoms. Visual loss occurred in 19 cases during the course of MS and 22 were found to have abnormal visual evoked potential (88%). The mean course of disease was 8.5 years (1.2-17.2) and 0-4 times of recurrences (0 means no new clinical attack occurred during following-up period).

CONCLUSIONSMS is increasingly recognized as a disease affecting children though it is uncommon. Childhood MS possesses some manifestations different from those of adults. There was a female predominance. The most common finding at the onset of disease was optic neuritis. Other features include acute onset and shorter course of disease. Atypical demyelinating symptoms were often seen. White matter lesions on MRI are required for the diagnosis. CSF oligoclonal bands could be found less commonly than in adults. Neurological sequelae were less often seen than in adults MS even though optic nerve atrophy and visual loss were relatively common. Steroid and IVIG are effective in acute period treatment.

Age of Onset ; Child ; Child, Preschool ; Demyelinating Diseases ; etiology ; Disease Progression ; Female ; Humans ; Immunoglobulins, Intravenous ; immunology ; Male ; Multiple Sclerosis ; immunology ; physiopathology ; therapy ; Optic Neuritis ; etiology ; immunology ; Secondary Prevention

Neuroimmunology is a rapidly expanding field in the medicine and there has been great advancement in the understanding of the pathogenesis of autoimmune diseases during the past decade. In neurology, immune mechanism has been implicated in the pathogenesis of more than twenty neurological diseases. The understanding of the immunological mechanism of these diseases has helped clinicians in management of these diseases. In many neurological diseases with immunological deterioration, multiple sclerosis and Guillain-Barre syndrome are relatively common diseases that share common features like demyelination. But multiple sclerosis is a disease of central nervous system and Guillain-Barre syndrome is a syndrome developed in peripheral nervous system. This review will describe the recent advances in clinical immunology with regard to general aspects of autoimmune diseases of neurological system, pathogenesis of two common autoimmune diseases, multiple sclerosis and Guillain-Barre syndrome.
Allergy and Immunology ; Autoimmune Diseases ; Central Nervous System ; Demyelinating Diseases ; Guillain-Barre Syndrome* ; Multiple Sclerosis* ; Neurology ; Peripheral Nervous System

No abstract available.
Animal ; Central Nervous System/virology ; Central Nervous System/pathology ; Central Nervous System/immunology ; Cytokines/metabolism ; Cytokines/immunology ; Demyelinating Diseases/virology* ; Demyelinating Diseases/immunology ; Disease Models, Animal ; Human ; Inflammation/virology ; Multiple Sclerosis/virology ; Multiple Sclerosis/immunology ; T-Lymphocytes/immunology ; Theiler Murine Encephalomyelitis Virus/pathogenicity ; Theiler Murine Encephalomyelitis Virus/immunology*

No abstract available.
Autoimmune Diseases/etiology ; Female ; Humans ; Multiple Sclerosis/etiology ; Papillomavirus Infections/*prevention & control ; Papillomavirus Vaccines/*adverse effects/*immunology ; Uterine Cervical Neoplasms/prevention & control