Antibodies to sulfatide in cerebrospinal fluid of patients with multiple sclerosis

The identity of target antigen(s) in multiple sclerosis (MS) remains elusive despite much effort to identify it. We analyzed cerebrospinal fluid (CSF) from patients with MS, other neurological diseases (OND), other diseases (OD) and healthy controls for antibodies against purified sulfatide, a major glycosphingolipid of human myelin, by an enzyme-linked immunosorbent assay (ELISA) and a thin-layer chromatogram (TLC)-immunostaining technique. Elevated anti-sulfatide antibodies were significantly higher in MS patients as compared with the OND group (p<0.05) and all controls combined (P<0.025). Binding of high titer antibodies to sulfatide was confirmed with TLC-immunostaining. Anti-sulfatide antibodies were detected in all subtypes of MS although the frequency was higher in patients with secondary progressive MS (SPMS) than in patients with primary progressive (PPMS) and relapsing-remitting MS (RRMS). The data demonstrate a humoral response to sulfatide in the CSF of patients with MS.     

Intrathecal levels of vitamin D and IgG in multiple sclerosis

Holmøy T, Lossius A, Gundersen TE, Moen SM, Castellazzi M, Fainardi E, Casetta I. Intrathecal levels of vitamin D and IgG in multiple sclerosis.
Acta Neurol Scand: 2012: 125: e28–e31.
© 2011 John Wiley & Sons A/S. Background – Intrathecal synthesis of IgG is a hallmark of multiple sclerosis (MS). Vitamin D may modulate B‐cell function and dampen the synthesis of IgG. Objective – To investigate the relation between vitamin D levels in cerebrospinal fluid and serum and intrathecal synthesis of IgG. Methods – 25‐hydroxyvitamin D (25(OH)D) and IgG were assessed in cerebrospinal fluid and serum in 40 patients with MS. Results – There was no significant correlation between the IgG index and 25(OH)D levels in cerebrospinal fluid or serum. The levels of 25(OH)D in cerebrospinal fluid and serum did not differ between patients with and without intrathecal synthesis of IgG. There was a non‐significant trend towards a positive correlation between the concentrations of 25(OH)D and IgG in the cerebrospinal fluid, but not in serum. Conclusion – Physiological variation in vitamin D does not exert a major impact on intrathecal synthesis of IgG in MS.     

High levels in serum, but no signs of intrathecal synthesis of anti-sulfatide antibodies in HIV-1 infected individuals with or without central nervous system complications.

Myelin degeneration is commonly found in the central nervous system (CNS) of individuals infected with human immunodeficiency virus type 1 (HIV-1), especially in patients with HIV-1-associated dementia. We analysed cerebrospinal fluid (CSF) and serum samples from 25 HIV-1 infected individuals for the presence of antibodies directed against sulfatide, the major acidic glycosphingolipid in myelin. Nine of the patients had CNS complications, including 3 with HIV-1-associated dementia, and 16 had no neurological symptoms. Elevated titres of anti-sulfatide antibodies were found in serum from 24/25 HIV-1-infected individuals but in none of them in the CSF. Although the vast majority of HIV-1-infected individuals harbour autoantibodies directed against sulfatide in serum, the lack of detectable intrathecal production indicates that anti-sulfatide antibodies are not a major component in the pathogenesis of CNS myelin damage in HIV-1 infection.     

Clinical features of Sjogren’s syndrome in patients with multiple sclerosis

Annunziata P, De Santi L, Di Rezze S, Millefiorini E, Capello E, Mancardi G, De Riz M, Scarpini E, Vecchio R, Patti F. Clinical features of Sjogren’s syndrome in patients with multiple sclerosis.
Acta Neurol Scand: 2011: 124: 109–114.
© 2010 John Wiley & Sons A/S. Objectives – To assess the frequency of clinical features of Sjogren’s syndrome (SS) in patients with multiple sclerosis (MS) receiving treatment with disease‐modifying drugs (DMDs) or naïve to treatment and the possible association with clinical, cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) parameters. Methods – A multicentre cross‐sectional observational study was designed, based on a structured neurologist‐administered questionnaire to 440 patients. Results – Twenty‐eight of 230 (12%) patients receiving treatment with DMDs (DMDs⁺) and 14 of 210 (6.6%) treatment‐naïve patients (DMDs⁻) showed clinical features of SS. Four primary SS were diagnosed, two of which were DMDs⁺ and two were DMDs⁻. Sicca symptoms were significantly associated with higher EDSS scores (P = 0.018), a low frequency of gadolinium‐enhanced MRI‐positive lesions (P = 0.018) and cerebral disturbances (P = 0.001). Conclusions – Screening for the clinical features of SS should be performed in patients with MS both receiving treatment with immunomodulatory drugs and without therapy.     

Impact of cladribine on soluble adhesion molecules in multiple sclerosis

Mitosek‐Szewczyk K, Stelmasiak Z, Bartosik‐Psujek H, Belniak E. Impact of cladribine on soluble adhesion molecules in multiple sclerosis.
Acta Neurol Scand: 2010: 122: 409–413.
© 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Background – Soluble forms of vascular cell adhesion molecule‐1 (VCAM‐1), intracellular adhesion molecule‐1 (ICAM‐1) and E‐Selectin play a role in the regulation of blood–brain barrier damage and represent markers of the clinical course of multiple sclerosis (MS) and magnetic resonance imaging activity. We determined sICAM, sVCAM and sE‐Selectin concentrations in the cerebrospinal fluid (CSF) and serum of patients with remitting–relapsing multiple sclerosis before and after cladribine treatment as well as in a control group. Methods – We examined 17 patients diagnosed according to McDonald’s criteria. Thirteen healthy age‐matched subjects served as controls. The ELISA method was used to measure sICAM‐1, sVCAM‐1 and sE‐Selectin. Results – The concentration of sICAM and sE‐Selectin decreased in sera (difference between patients and controls was statistically significant, in the former P < 0.04, in the latter P < 0.0003) but not in the CSF of MS patients after cladribine treatment. Conclusions – The reduction in sICAM and sE‐Selectin concentrations after cladribine treatment indicates an immuno‐suppressive effect of the drug. The changes in levels of sICAM and sE‐Selectin after cladribine treatment reflect disease activity and indicate a reduction in the inflammatory reaction.     

Multiple sclerosis in Vest-Agder County, Norway

Vatne A., Mygland Å., Ljøstad U. Multiple sclerosis in Vest‐Agder county, Norway.
Acta Neurol Scand: 2011: 123: 396–399.
© 2010 John Wiley & Sons A/S. Objective – To examine multiple sclerosis (MS) prevalence, rate of immunomodulatory treatment and frequency of Borrelia Burgordorferi (Bb) antibodies in Vest‐Agder, Norway. Materials and methods – Patients in the period 1996–2006 who met the Poser criteria for definitive or probable MS were included. Clinical and demographical data, and presence of Bb antibodies were registered. Results – A total of 295 patients were identified. The crude prevalence was 180 per 100,000 population (95% CI = 160.9–218.0), age‐adjusted prevalence was 186 per 100,000 population (95% CI = 166.3–225.3). The age‐adjusted incidence rates were 7.5 and 8.0 for 1996–2000 and 2001–2006, respectively. Thirty‐eight per cent were treated with immunomodulatory agents when compared to 28% in the rest of the country. Bb serum antibodies were detected in 7% of patients with MS. Conclusions – Vest‐Agder county has the highest prevalence of MS reported in Norway, and a high treatment rate. Bb antibodies were not more prevalent than in healthy individuals.     

Antibodies against light neurofilaments in multiple sclerosis patients

OBJECTIVES: Axonal damage in multiple sclerosis (MS) may be reflected by antibodies against axon-specific proteins - the light subunit of neurofilaments (NFL). MATERIALS AND METHODS: The serum and cerebrospinal fluid obtained from 58 MS patients, 24 normal controls (CN), 49 control patients with miscellaneous diseases (CD) and 31 patients with neurodegenerative disorders (CDEG) were tested for both immunoglobulin G and M antibodies against NFL, using an ELISA. RESULTS: Intrathecal IgG antibodies to NFL were elevated in MS patients compared with that in CD patients (P = 0.001) and were not related to clinical variables. No differences in IgM anti-NFL levels were found between the MS and CN/CD groups. IgM to NFL was higher in the CDEG group than in either the CD group or even the MS group (P < 0.0005). CONCLUSIONS - Intrathecal IgM or IgG antibodies to NFL are not useful surrogate markers for axonal damage or disease subtypes in MS.     

Increased cerebrospinal fluid chitotriosidase index in patients with multiple sclerosis

Verbeek MM, Notting EA, Faas B, Claessens‐Linskens R, Jongen PJH. Increased cerebrospinal fluid chitotriosidase index in patients with multiple sclerosis.
Acta Neurol Scand: 2010: 121: 309–314.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective – To investigate chitotriosidase (CTTS) activity in serum and cerebrospinal fluid (CSF) in multiple sclerosis (MS) patients in relation to disease course and CSF markers for immune activation or inflammation. Materials and methods – We studied 80 patients with relapsing–remitting MS (RRMS), 24 with secondary progressive MS (SPMS), 20 with primary progressive MS (PPMS) and 29 patients with other neurological disorders (OND). We measured CTTS activity and studied the correlation with CSF mononuclear cell count (MNC) and intrathecal IgG production. Results – CTTS activity was significantly higher in CSF, but not in serum, from the total MS group compared with OND and controls. In RRMS and SPMS CTTS, index was increased compared with controls (RRMS, 0.10 ± 0.21; SPMS, 0.10 ± 0.15; controls, 0.021 ± 0.020), but not in PPMS (0.061 ± 0.052). CTTS index was higher in MS patients with elevated MNC or CSF‐restricted oligoclonal IgG bands than in MS patients without these CSF findings. Conclusions – CTTS index is elevated in RRMS and SPMS. The CTTS index is related to CSF markers of inflammation or immune activation.     

Elevated HSP27 levels during attacks in patients with multiple sclerosis

Ce P, Erkizan O, Gedizlioglu M. Elevated HSP27 levels during attacks in patients with multiple sclerosis.
Acta Neurol Scand: 2011: 124: 317–320.
© 2011 John Wiley & Sons A/S. Objectives – The small heat shock protein, HSP27, has been shown to have a more potent protective effect in the nervous system. However, there is limited information about the behavior of HSP27 in the course of multiple sclerosis (MS). Thus, we investigated the HSP27 levels during relapse and remission phases of MS. Materials and Methods – A total of 50 relapsing–remitting or secondary progressive MS patients and 45 age‐ and gender‐matched controls without any systemic diseases were enrolled. HSP27 levels were serologically detected in serum samples of both controls and MS patients during acute attacks and after a minimum of 2 months of each individual attack. Results – The mean HSP27 level was 12.41 ± 18.21 ng/ml in the attack phase, 4.58 ± 4.75 ng/ml during remission, and 2.58 ± 3.88 ng/ml in control patients. The heat shock proteins (HSP) levels of MS patients in the attack phase were significantly higher than those obtained in the remission phase (P = 0.005). Moreover, HSP levels in the attack and remission phases of MS patients were also significantly higher when compared to controls (P = 0.001 and P = 0.03, respectively). While there was no correlation between HSP27 levels in the attack phase and age, disease duration, or expanded disability status scale scores (P = 0.69, P = 0.32, and P = 0.91, respectively), a positive correlation was observed between the HSP27 levels and the total attack number (P = 0.001). Conclusions – Our findings revealed a marked elevation in HSP27 levels during the relapse phase. Therefore, it can be suggested that elevated HSP27 levels may guide in the accurate detection of an attack in patients with MS.     

Immunological differentiation between neuroborreliosis and multiple sclerosis

Summary Neuroborreliosis, a tick-borne spirochaetosis of the central nervous system, is diagnosed by the presence of intrathecally synthesized Borrelia burgdorferispecific antibodies. Multiple sclerosis and neuroborreliosis can show similarities in clinical symptoms as well as lymphocytic cell reactions and oligoclonal bands in the isoelectric focusing of cerebrospinal fluid. To differentiate between multiple sclerosis and neuroborreliosis we tested intrathecally synthesized IgM and virus antibodies. The IgM indices were higher for most of the neuroborreliosis patients studied than for those with multiple sclerosis, and cell counts were also significantly higher in the acute stage of the disease. In 84% of multiple sclerosis patients we were able to demonstrate intrathecal antibody production against measles, rubella or mumps virus. Neuroborreliosis patients had no intrathecal virus antibody synthesis. The specification of oligoclonal bands resulting from isoelectric focusing of cerebrospinal fluid with an ELISA for B. burgdorferi can further substantiate the diagnosis of neuroborreliosis or help to rule it out in multiple sclerosis patients with positive borreliaspecific serology.     

Antimyelin basic protein and antimyelin antibody-producing cells in multiple sclerosis.

The B-cell response to myelin and myelin basic protein was studied in patients with multiple sclerosis and in patients with acute aseptic meningoencephalitis by using a nitrocellulose immunospot assay. This method allows detection of single cells producing antibodies. Twenty-seven (79%) of 34 patients with multiple sclerosis had cells producing IgG antibodies against myelin, and 11 (57%) of 19 had cells producing IgG antibodies against myelin basic protein in cerebrospinal fluid (CSF), with mean values of 30 and 14 per 10(4) mononuclear cells, respectively. Total numbers of IgG-producing cells occurred at a mean number of 75 per 10(4) CSF cells. Cells producing antimyelin or anti-myelin basic protein antibodies of IgA or IgM isotypes were rarely found in CSF. Patients with acute aseptic meningoencephalitis less frequently showed CSF cells producing IgG antibodies against myelin and myelin basic protein. No cells producing antibodies against myelin or myelin basic protein were detected in peripheral blood of patients with multiple sclerosis or meningoencephalitis. Thus, a majority of patients with multiple sclerosis had CSF cells that produced IgG antibodies against myelin and myelin basic protein. These cells comprised a large proportion of the total IgG-producing cells. A pronounced B-cell response against autoantigens produced at the target for immune attack might be important in the pathogenesis of multiple sclerosis.     

Viral IgM antibodies in serum and cerebrospinal fluid in patients with multiple sclerosis and controls

Serum and cerebrospinal fluid (CSF) from 28 patients with multiple sclerosis (MS), 14 with other neurological diseases (OND) and 31 control subjects with tension headache were analysed for presence of IgM antibodies against measles, mumps and varicellae zoster by a specific enzyme-linked immunosorbent assay (ELISA). This technique excluded false positive reaction due to possible presence of rheumatoid factor. Twelve of the 28 patients with MS had IgM antibodies in serum and 4 in CSF, the latter always being accompanied by presence of corresponding IgM antibodies in serum. Six patients had mumps specific IgM, 5 had measles specific IgM and 3 varicellae specific IgM. In 2 patients, viral IgM antibodies were demonstrated in serum against 2 different viruses. Among the 14 OND patients, one with Wilson's disease had demonstrable serum IgM varicellae antibodies and one with radicultis had elevated serum and CSF measles and varicellae IgM antibodies. Among 31 controls, 2 had IgM antibodies in serum, one against varicellae and one against mumps. No correlations were found between viral IgM antibodies and CSF IgM index, serum IgM levels or blood-brain barrier state. Our data show that MS may be accompanied by a systemic IgM response against the 3 viruses tested, occasionally against 2 of the 3 different viruses simultaneously. The occurrence in MS of virus-specific IgM may be a reflection of viral reactivation and/or polyclonal B cell activation.     

Interleukin‐17 and interleukin‐23 are elevated in serum and cerebrospinal fluid of patients with ALS: a reflection of Th17 cells activation?

Rentzos M, Rombos A, Nikolaou C, Zoga M, Zouvelou V, Dimitrakopoulos A, Alexakis T, Tsoutsou A, Samakovli A, Michalopoulou M, Evdokimidis J. Interleukin‐17 and interleukin‐23 are elevated in serum and cerebrospinal fluid of patients with ALS: a reflection of Th17 cells activation?
Acta Neurol Scand: 2010: 122: 425–429.
© 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Background – There is evidence that immunological factors may involved in pathogenetic mechanisms of amyotrophic lateral sclerosis (ALS). Th17 cells are characterized by predominant production of IL‐17 and are suggested to be crucial in destructive autoimmunity. Interleukin‐23 (IL‐23) appears to play a supporting role in the continued stimulation and survival of Th17. Patients and methods – We measured by enzyme‐like immunosorbent assay (ELISA) serum and cerebrospinal fluid (CSF) levels of IL‐17 and IL‐23 in 22 patients with ALS and 19 patients with other non‐inflammatory neurological disorders (NIND) studied as a control group. IL‐17 and IL‐23 serum and CSF levels were also correlated with duration of the disease, the disability level and the clinical subtype of the disease onset in patients with ALS. Results – IL‐17 and IL‐23 serum levels were higher in patients with ALS as compared with patients with NIND (P = 0.015 and P = 0.002 respectively). IL‐17 and IL‐23 CSF levels were also increased in patients with ALS (P = 0.0006 and P = 0.000001 respectively). IL‐17 and IL‐23 levels were not correlated with disease duration, disability scale or clinical subtype of the disease onset in ALS patients. Conclusions – Our findings suggest that these molecules may be involved in the pathogenetic mechanisms acting as potential markers of Th17 cells activation in ALS.     

Myelin flow cytometry assay detects enhanced levels of antibodies to human whole myelin in a subpopulation of multiple sclerosis patients

Antibodies directed against myelin components have been described in multiple sclerosis (MS). Accumulating evidence suggests that pathogenically relevant anti-myelin antibodies bind conformational and post-translationally modified epitopes. However, the current methods to detect anti-myelin antibodies often do not allow recognition of such epitopes. We developed a flow cytometry-based assay to detect antibodies to whole human myelin (including conformational and post-translationally modified epitopes). MS patients (n=152) showed enhanced serum levels of anti-myelin antibodies (total Ig, IgG and IgM) when compared to healthy donors (HD, n=40). Strikingly, approximately 50% of MS patients showed enhanced anti-myelin IgG levels. Anti-myelin IgG levels were not correlated with clinical parameters of disease. In the same population, serum antibody responses to recombinant myelin oligodendrocyte glycoprotein were comparable in MS patients and HD.     

Elevated levels of antibody to myelin oligodendrocyte glycoprotein is not specific for patients with multiple sclerosis

OBJECTIVE: To evaluate the presence and specificity of anti-myelin oligodendrocyte glycoprotein (MOG) antibody in the cerebrospinal fluid and plasma of patients with multiple sclerosis (MS). DESIGN: Case-control study of patients with clinically definite MS compared with patients with other neurologic diseases (ONDs) of the central nervous system and control subjects. SETTING: Referral center in the Department of Neurology of Hadassah University Hospital, greater Jerusalem area, Israel. PARTICIPANTS: Consecutive cerebrospinal fluid samples from 31 patients with MS, 31 patients with ONDs, and 28 healthy controls; and plasma samples from 33 patients with MS, 28 patients with ONDs, and 31 healthy controls were taken from the cerebrospinal fluid and plasma bank of the Department of Neurology, Hadassah University Hospital. MAIN OUTCOME MEASURES: Levels and frequencies of anti-MOG antibody in patients with MS, as defined by enzyme-linked immunosorbent assay. RESULTS: Cerebrospinal fluid levels of antibodies to MOG and to myelin basic protein were significantly higher in patients with MS (P<.001 and P = .001, respectively) and patients with ONDs (P = .005 and P = .03, respectively) compared with controls; frequency of antibodies to MOG, but not to myelin basic protein, was higher in patients with MS and patients with ONDs (P = .01 and P = .003, respectively, for the frequency of anti-MOG antibody, and P = .65 and P = .41, respectively, for the frequency of anti-myelin basic protein antibody). Plasma levels of antibodies to MOG and to myelin basic protein were higher in patients with MS compared with patients with ONDs (P = .003 for both comparisons) and with controls (P = .03 and P = .04, respectively); however, the frequency of antibodies to MOG and myelin basic protein was similar in patients with MS, patients with ONDs (P=.54 and P = .82, respectively), and controls (P = .50 and P = .14, respectively). CONCLUSIONS: The elevated presence of anti-MOG antibody is not specific for MS because a similar appearance was also demonstrated in patients with ONDs. Therefore, it is not clear whether this antibody is pathogenic in MS or, on the contrary, has a defensive role against further immune-mediated damage after myelin breakdown.     

Binding properties of cerebrospinal fluid IgG in multiple sclerosis and other neurological diseases

A solid phase radioimmunoassay (RIA) was used to detect antibodies to myelin or myelin basic protein (MBP) in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) or other neurological diseases (OND). When measured at the same IgG concentration, MS samples had higher binding values than OND against myelin, but not against MBP. Using F(ab')2 fragments purified from pools of MS and OND CSF there was no difference in binding to myelin between MS and OND samples. These results indicate that anti-MBP antibodies are nt a feature of MS and binding of CSF IgG to myelin is not due to specific antibody, but is probably the result of non-specific binding to Fc receptors.     

Multiple specificities of antibrain antibodies in multiple sclerosis and chronic myelopathy

The presence of complement-fixing antibodies against brain antigens was tested in paired serum and cerebrospinal fluid (CSF) samples from 60 multiple sclerosis (MS) patients, 15 patients with chronic myelopathy of undetermined cause (CM) and 60 control patients. Six MS sera, 34 MS CSF, 4 CM sera, 3 CM CSF, 4 control sera and 1 control CSF gave positive reactions either with a lipid extract or a saline extract of normal human brain. The proportion of anticomplementary CSF was significantly higher in the MS group than in the control group (15% vs 0%, P < 0.01). The reactivity of a large number of individual positive samples was further investigated. Seven antibody specificities were discerned in the MS samples. Most samples reacted with nonlipid antigens, the dominating being a heat-labile, nonlipid component associated with CNS myelin. Antibodies to cerebroside and sulfatide were detected in a few patients. A number of samples reacted with cholesterol in combination with a variety of lipids. Positive samples from the CM patients exhibited a similar heterogeneity. In the control group positive reactions were seen in one patient with systemic lupus erythematosus (SLE), two patients with rheumatoid arthritis (RA), and one with a spinal meningioma. The reaction patterns of these patients were different from those commonly seen in MS patients. The complement-fixing antibrain antibodies in MS CSF are usually of IgG class (Ryberg 1976). This applies also to the positive MS sera in this study. The distribution of the antibodies between serum and CSF indicated, in several cases, an intrathecal synthesis. All of a number of human brains, including one MS brain, contained all 6 antigens (haptens) reactive in saline extracts. Antibodies to tissues outside the CNS were rarely detected in MS patients. The varied humoral autoimmune response in MS might reflect a heterogeneity in the MS patients, the disease itself or its causative agent.     

Comparison of carbamazepine rash in multiple sclerosis and epilepsy

Shirzadi M, Alvestad S, Hovdal H, Espeset K, Lydersen S, Brodtkorb E. Comparison of carbamazepine rash in multiple sclerosis and epilepsy.
Acta Neurol Scand: 2012: 125: 60–63.
© 2011 John Wiley & Sons A/S. Objectives – Studies on the comorbidity of multiple sclerosis (MS) and allergic disorders have shown conflicting results. Carbamazepine (CBZ) is widely used in MS to control pain. We have compared the incidence of rash from CBZ use in MS and epilepsy. Materials and Methods – Consecutive adult patients with MS and epilepsy were studied retrospectively. A detailed survey of medical records concerning CBZ treatment was performed. Results – A total of 495 patients with epilepsy and 442 patients with MS were included. Sixty‐five per cent of patients with epilepsy and 20% of patients with MS had used CBZ. In CBZ‐exposed patients, rash occurred in 15/89 (17%) in MS and in 43/323 (13%) in epilepsy, a difference which was not significant. Women below 50 years experienced more skin reactions than older women and men. The unadjusted odds ratio (OR) for rash in the MS vs epilepsy group was 1.32 (CI 0.70–2.51, P = 0.40). Adjusting groups for gender and age reduced the OR to 1.11 (CI 0.56–2.19, P = 0.76). Conclusion – Compared with epilepsy, which is only rarely caused by immunological mechanisms, the autoimmune disorder MS was not associated with a different occurrence of CBZ skin reactions. The trend towards an increased occurrence of rashes in MS can partly be explained by a higher predisposition to CBZ rash in women of fertile age.     

多发性硬化与髓鞘抗体及髓鞘碱性蛋白

探讨多发性硬化的免疫发病机制。方法采用ELISA方法测定多发性硬化患者活动期血清（28例）和脑脊液（18例）的GM1抗体、脑磷脂抗体和髓鞘碱性蛋白。结果多发性硬化患者血清GM1抗体阳性率为36％,脑磷脂抗体为43％;脑脊液GM1抗体为11％,脑磷脂抗体为18％,与对照组比较差异均有显著性;血清和脑脊液的髓鞘碱性蛋白增高亦有意义。结论体液免疫参与了多发性硬化的发病过程。可能的机制是,针对自身组织的髓鞘蛋白、髓鞘脂质等自身免疫系统被激活,产生一系列病理改变和临床症状。     

A potential role for human herpesvirus type 6 in nervous system disease

Human herpesvirus type 6 (HHV-6) is a new representative of the herpesvirus family which was associated with a spectrum of diseases, including myalgic encephalitis, meningitis and the chronic fatigue syndrome. We set out to study the potential role of HHV-6 in multiple sclerosis (MS) (n = 21), facial palsy (FP) (n = 19) and Guillain-Barré-syndrome (GBS) (n = 7). Results were compared with a control group (CG) (n = 16). We analyzed paired samples of serum and cerebrospinal fluid (CSF) with the polymerase chain reaction (PCR) for the presence of HHV-6 DNA. The studies were complemented by ELISA determination of serum antibodies against HHV-6. In the MS group we detected HHV-6 DNA in the CSF from three of 21 (14.3%) patients but not in the corresponding serum samples. In FP, GBS and controls CSF and serum PCRs were negative in all cases. HHV-6 serum antibody titers were significantly higher in MS compared with FP, GBS and controls. These findings suggest that HHV-6 may play a role in MS.