Oligoclonal IgG Bands Research Articles

Associations of HLA DRB1 alleles with IgG oligoclonal bands and their influence on multiple sclerosis course and disability status

Background and aimOligoclonal bands (OCB) may be associated with the genes of HLA complex, which allows to consider the possible interaction of genetic and immunological factors and its importance in the development and progression of multiple sclerosis (MS). The aim of this study was to evaluate the associations between HLA DRB1 alleles and oligoclonal bands (OCBs) in the disease course and disability of multiple sclerosis (MS) patients. Materials and methodsThis was a prospective study of 120 patients with MS. HLA DRB1 alleles were genotyped using the polymerase chain reaction. Matched cerebrospinal fluid (CSF) and plasma samples were analyzed using isoelectric focusing and IgG specific immunofixation to test for the presence of intrathecal specific OCB. ResultsHLA DRB1*08 allele was related to a lower degree of disability. Oligoclonal bands were an independent and significant factor that influenced disability status irrespective of HLA DRB1* 04, *07, *08, *13, *15 and *16 alleles. Age at the onset and duration of the disease were independent and significant factors for MS progression in all logistic regression models with each newly added HLA DRB1 allele. HLA DRB1*08 allele was related to 75% lower odds that relapsing remitting (RR) MS will change to a progressive course MS irrespective of the other factors investigated. Detection of OCBs in the CSF was associated with the higher possibility of RR MS progression in all cases, except when the *08 allele was present. ConclusionsOCBs had an influence on disability status, while HLA DRB1*08 allele was significantly associated with lower possibility that RR MS will change to progressive course MS.

Opsoclonus-myoclonus syndrome in adults: a report of two cases

Background: Opsoclonus-myoclonus syndrome (OMS) is a rare movement disorder characterized by chaotic multidirectional eye movements, myoclonus and less frequently cerebellar ataxia. OMS affects as few as 1 in 10,000,000 people per year. Case reports: We present two cases of female Caucasian patients aged 19 and 60 years respectively who developed OMS following a febrile illness. In both cases OMS starts with an acute flare-up of physical symptoms within days. The neurologic examination revealed opsoclonus, myoclonus and ataxia. Both women had normal magnetic resonance imaging of the brain. The results of routine laboratory tests were normal. In both cases, cerebrospinal fluid examinations was consistent with aseptic meningoencephalitis and showed cell-protein association (lymphocytic pleocytosis and protein elevation). The oligoclonal IgG band was negative. Cytomegalovirus, Epstein-Bar virus, Varicella-zoster virus, borrelia, coxsackie, enterovirus, streptococcal infection, syphilis, herpes simplex virus-1 and -2, human immunodeficiency virus or hepatitis were negative in the serological tests. The thyroid function tests, the tests for anti-nuclear and anti-neuronal antibodies were within normal limits. Malignancy was not detected on positron-emission tomography-CT. After therapies including a combination of intravenous methylprednisonolon, intravenous ceftriaxon, acyclovir and clonazepam, both patients gradually improved and had recovered. After a 12-month follow-up, both women had no neurological sequelae. We have obtained approval of both patients. Conclusion: OMS is associated with multiple etiologies. The most common etiologies are idiopathic, paraneoplastic and infectious disorders. OMS may occur in patients with aseptic brainstem encephalitis. The exact immunopathogenesis and pathophysiology of OMS are uncertain.

Free kappa light chains in cerebrospinal fluid as a biomarker to assess risk conversion to multiple sclerosis.

BackgroundMultiple sclerosis (MS) initiates with a first attack or clinically isolated syndrome (CIS). The importance of an early treatment in MS leads to the search, as soon as possible, for novel biomarkers which can predict conversion from CIS to MS.ObjectiveThe purpose of this study was to assess the predictive value of the kappa index ( index), using kappa free light light chains (FLCs) in cerebrospinal fluid (CSF), for the conversion of CIS patients to MS, and compare its accuracy with other parameters used in clinical practice.MethodsFLC levels were analysed in CSF from 176 patients: 70 as control group, 77 CIS, and 29 relapsing–remitting MS. FLC levels were quantified by nephelometry.Results Index sensitivity and specificity (93.1%; 95.7%) was higher than those from the immunoglobulin G (IgG) index (75.9%; 94.3%), and lower than those from oligoclonal IgG bands (OCGBs) (96.5%; 98.6%). The optimal cut-off for index was 10.62. Most of the CIS patients with index >10.62 presented OCGBs, IgG index >0.56 and fulfilled magnetic resonance imaging (MRI) criteria.ConclusionCIS patients above index cut-off of 10.62 present 7.34-fold risk of conversion to MS than CIS below this value. The index correlated with positive OCGBs, IgG index above 0.56 and MRI criteria.

OP64 – 2760: Oligoclonal bands predict multiple sclerosis in children with isolated optic neuritis

Background Isolated optic neuritis (ON) in childhood may remain a single episode or mark the clinical beginning of multiple sclerosis (MS). Higher age and pathological cranial MRI (cMRI) at presentation were previously demonstrated as independent risk factors of conversion to MS. Objective To further evaluate potential MS risk factors, including cerebrospinal fluid findings (CSF), in children with ON as a first demyelinating event. Methods Children with isolated uni- or bilateral ON as a first demyelinating event below age 18 were included in this retrospective multicenter cohort study. The minimal follow-up (FU) for those not converting to MS according to McDonald 2010 was 2 years. Age, sex, laterality of ON, cMRI (no vs ≥1 MS-compatible lesion outside the optic nerves) and intrathecal oligoclonal IgG bands (OCB) were assessed as risk factors using simple and multiple Cox proportional-hazards regressions. Results Of 357 included children 284 had uni- and 73 bilateral isolated ON. Median FU of patients not developing MS was 4.2 years (range 2.0–22.0). Univariate analyses revealed age (HR 1.15, 95% CI 1.10–1.22, p Conclusion Cerebrospinal fluid analysis may supplement cMRI to determine the risk of MS in children with isolated ON as a first demyelinating event.

A nationwide survey of combined central and peripheral demyelination in Japan

ObjectivesTo clarify the clinical features of combined central and peripheral demyelination (CCPD) via a nationwide survey.MethodsThe following characteristics were used to define CCPD: T2 high-signal intensity lesions in the brain,...

The active intrathecal B-cell response in LGI1-antibody encephalitis

BackgroundLeucine-rich glioma inactivated 1 (LGI1) is a component of the voltage-gated potassium channel complex. IgG antibodies against LGI1 are associated with immunotherapy-responsive encephalitis and epilepsies. LGI1-antibody concentrations are 10–100 times greater in serum than in cerebrospinal fluid (CSF). Oligoclonal IgG bands are rarely found in patients with LGI1-antibody encephalitis or epilepsy. These observations raise questions about the sources of the B cells that result in production of LGI1 antibodies and how the IgGs reach the brain. We aimed to investigate the migration and expansions of peripheral and central B cells to the production of LGI1-specific IgG. MethodsWe performed PCR amplification and next generation deep immune repertoire sequencing of immunoglobulin (Ig) heavy chain variable regions (VH) from CSF and subsorted peripheral blood B-cell populations from two patients with limbic encephalitis and faciobrachial dystonic seizures associated with LGI1 antibodies. Bioinformatics clustering of related IgM-VH or IgG-VH transcripts was used to determine whether active B-cell diversification could be observed, and whether intrathecal B-cell repertoires, if present, were related to peripheral B cells. FindingsWe identified clusters of related Ig-VH transcripts in the CSF of both patients. Within these clusters there was a range of somatic hypermutations along the IGHV germline segment-derived portion. In addition, we identified a large number of closely related Ig-VH clusters that were common to both CSF and peripheral blood, including a small number of dominating Ig-VH clusters that might represent the most active clonally related B-cell populations. InterpretationOur data suggest that some B-cell affinity maturation occurs inside the CNS compartment in LGI1-antibody encephalitis. Somatic hypermutation rates point to a CSF antigen-driven activation of clonally related B cells that shape the intrathecal immune repertoire. The target antigen or antigens of these clonally related B cells remain unknown; our work continues to determine the relative contribution of intrathecally activated and peripheral LGI1-specific B cells in this autoimmune CNS disease. FundingWellcome Trust Intermediate Fellowship to SRI, Fulbright-MS Society, Epilepsy Research UK, BMA Vera Down Research Grant.

Latitude and HLA-DRB1 alleles independently affect the emergence of cerebrospinal fluid IgG abnormality in multiple sclerosis

Background: It is unclear whether the prevalence of oligoclonal IgG bands (OCBs) in multiple sclerosis (MS) is different between northern and southern regions of Asia. Objective: This study aimed to compare the prevalence of OCBs and positive cerebrospinal fluid (CSF) findings between northern and southern regions of Japan and to investigate the association of these CSF findings with HLA-DRB1 alleles. Methods: The study included 180 MS patients from Hokkaido (northern Japan) and 184 patients from Kyushu (southern Japan). The IgG index was defined as increased if it was >0.658. Presence of CSF OCBs and/or increased IgG index was defined as positive CSF findings. Results: Positive CSF findings and OCB positivity were significantly higher in MS patients from Hokkaido than in those from Kyushu (p < 0.0001 for both). Logistic regression analysis revealed that after adjusting for covariates that can be related to abnormal CSF IgG production, the geographic region (Hokkaido) showed odds ratios (ORs) of 4.08 and 2.57, whereas the HLA-DRB1*04:05 allele showed ORs of 0.36 and 0.30 for positive CSF findings and OCB positivity, respectively. Conclusions: The results indicate that latitude and HLA-DRB1 alleles independently affect the emergence of CSF IgG abnormalities in Japanese patients with MS.

Epstein-Barr virus-specific intrathecal oligoclonal IgG production in relapsing-remitting multiple sclerosis is limited to a subset of patients and is composed of low-affinity antibodies.

BackgroundThe purpose of this study was to investigate intrathecal production and affinity distributions of Epstein-Barr virus (EBV)-specific antibodies in multiple sclerosis (MS) and controls.MethodsCerebrospinal fluid (CSF) and serum concentrations, quantitative intrathecal synthesis, oligoclonal bands (OCB) patterns and affinity distributions of anti-Epstein Barr virus (EBV) antibodies were evaluated in 100 relapsing-remitting MS (RRMS) patients and 200 age- and sex-matched controls with other inflammatory neurological disorders (OIND) and other noninflammatory neurological disorders (NIND).ResultsLevels of anti-EBNA-1 and anti-viral capsid antigen (VCA) IgG were different in both the CSF (P <0.0001 and P <0.01, respectively) and serum (P <0.001 and P <0.05, respectively) among the RRMS, OIND and NIND. An intrathecal synthesis of anti-EBNA-1 IgG and anti-VCA IgG, as indicated by the antibody index, was underrepresented in the RRMS, OIND and NIND (range 1 to 7%). EBV-specific OCB were detected in 24% of the RRMS patients and absent in the controls. High-affinity antibodies were more elevated in the RRMS and in the OIND than in the NIND for CSF anti-EBNA-1 IgG (P <0.0001) and anti-VCA IgG (P <0.0001). After treatment with increasing concentrations of sodium thiocyanate, the EBV-specific IgG OCB had low affinity in all 24 RRMS patients analyzed.ConclusionsOur findings do not support the potential role of an EBV persistent brain chronic infection in MS and suggest that an EBV-specific intrathecal oligoclonal IgG production can occur in a subset of MS patients as part of humoral polyreactivity driven by chronic brain inflammation.

CIS diagnostics and predictors of conversion to CDMS

Clinically isolated syndrome (CIS) is a term used to define an episode suggestive of central nervous system (CNS) inflammatory demyelination. The majority of CIS will evolve to multiple sclerosis (MS), a chronic disease characterised by further relapses and accumulation of disability. Current evidence suggests that disease modifying treatment (DMT) should be started at early stages since it is likely to have a significant impact on the evolution of the disease. Thus, accurately identifying which patients will remain as CIS or which will develop MS and, above all, determining the degree of disability they could develop over the mid- to long term is considered crucial for a more individualized treatment. Natural history studies have shown that a younger age at disease onset is related to a higher risk of conversion to clinically definite MS (CDMS) and that male gender is associated to a higher disability accumulation as measured by the Kurtzke Expanded Disability Status Scale (EDSS). Among clinical factors, CIS patients presenting with an optic neuritis have been related to a lower risk of developing both MS and disability accumulation in comparison to CIS affecting other topographies. Regarding biological factors, a recent meta-analysis showed that presence of IgG oligoclonal bands (OB) increases both the risk of having a second attack and the risk of disability accumulation. To date, brain MRI remains the most reliable prognostic marker for developing MS or disability. It has been demonstrated that a higher number of brain T2 lesions or Barkhof criteria (BC) on baseline MRI increases the risk of developing MS and disability in the mid- to long term. However, although the abovementioned natural history studies are indeed based on large multicentre cohorts with long follow-up, they have a number of limitations: they usually comprised data obtained both retrospectively and prospectively, which could lead to information bias. Baseline and follow-up visits do not follow a standardized protocol, compromising the homogenization among the different centres of the data acquired. Absence of MRI data is frequent and when present, a systematic MRI protocol is lacking. These limitations often result in the fact that MRI and OB have not been taken into account as joint covariates in the models. Finally, quantification of patients lost to follow-up and its causes are not registered, leading to survival bias. On the other hand, the longitudinal MRI cohorts have a small sample size, follow-up is not regular, and optic neuritis is frequently over-represented, deeming subgroup analyses impossible. Overcoming some of these limitations, I will present the Barcelona inception cohort study on 1000 CIS. We have tried to identify and stratify which baseline demographic, clinical, radiological or biological factors predict MS development and disability accumulation in a unique multivariate approach on a large prospective cohort.

Cerebrospinal fluid immunological biomarkers associated with axonal damage in multiple sclerosis.

Cerebrospinal fluid (CSF) neurofilament light protein (NFL) is a promising biomarker of axonal injury and neurodegeneration. Here CSF lymphocyte subpopulations and antibodies, potential players of neurodegeneration, are examined in relation to CSF NFL shedding in MS. Cerebrospinal fluid NFL from 127 consecutive untreated MS patients was analysed. Samples from 37 age-matched patients with other central nervous system non-inflammatory neurological diseases (NIND) were also assessed. CD4+, CD8+, CD56+ and CD19+ cell subsets were studied by flow cytometry. Oligoclonal IgG and IgM bands (OCMB) against lipids were studied by isoelectric focusing and immunoblotting. These data were analysed in relation to clinical and magnetic resonance imaging features. A CSF NFL cut-off value of 900ng/l (mean+3 SD of NIND values) was calculated. MS patients with increased NFL values showed significantly higher Multiple Sclerosis Severity Score and magnetic resonance imaging lesion number. The presence of OCMB (P<0.0001) and elevated T and B lymphocyte counts was associated with increased levels of CSF NFL. High CSF NFL levels are associated with elevated CSF lymphocyte cell counts and intrathecal synthesis of IgM against lipids. These findings support a role for OCMB in the axonal damage of MS offering a rationale for the association of these antibodies with disability and brain atrophy progression in MS.

Inflammation Inducing Central Nervous System Damage in HTLV-1 Infection

Human T-cell lymphotropic virus type 1 (HTLV-1) is involved with two well-described clinical conditions: HTLV-1-associated myelopathy/ tropical spastic paraparesis (HAM/TSP) and adult T cell leukemia. The neurological disease affects predominantly the spinal cord. Although unusual, the brain as well as other organs may be involved by inflammatory reaction associated with HTLV-1 infection. This condition was recently described in our report “Temporal lesions and widespread involvement of white matter associated with multi-organ inflammatory disease in human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)”. The development of HTLV-1-associated diseases seems to be regulated by viral, host and environmental determinants. High proviral load (PVL) is the best predictor of HAM/TSP. Proviral integration into transcriptionally active units in host genomes and genotypes HLA-B*5401 and HLA-DRB1*0101 are associated with high PVL and consequently linked to HAM/TSP. The increased proliferation and migration of HTLV-1 infected lymphocytes to central nervous system and a resulting strong pro-inflammatory reaction play a crucial role in the neuropathogenesis of the disease. In general, increasing in HTLV-1 PVL in both peripheral blood mononuclear cells and in cerebrospinal fluid (CSF) cells coincides with the exacerbation of neurological symptoms. Analysis of CSF in HAM/TSP shows an inflammatory response characterized by lymphocytic pleocytosis, raised protein content, intrathecal synthesis of oligoclonal IgG bands and of specific IgG, and increased concentration of pro-inflammatory markers. Here, it will be discussed the pathogenesis and the inflammatory mechanisms leading to injury of the central nervous system in HTLV-1 infection.

K Index in cerebrospinal fluid: a valid tool in multiple sclerosis diagnosis

Detection of oligoclonal IgG bands in cerebrospinal fluid by isoelectrocfocusing and immunodetection is the current gold standard to detect an inflammatory process in the central nervous system. It has been proposed that the presence of free light chains (FLCs) in CSF was associated with recent demyelination activity in MS and might be used as a prognosis marker. Our study’s objective is assessing the diagnostic accuracy of a new highly sensitive latex-enhanced nephelometric assay for k free light chain (kFLC) determination in CSF/serum as an alternative to traditional tests and its clinical application. kFLCs were measured in CSF/serum pairs from 80 patients by the use of a new highly sensitive latex-enhanced nephelometric automated immunoassay for detection of immunoglobulin FLC. The eighty patients were split into three groups according to the neurological diagnosis. In this study we confirm even more the use of the k Index as a diagnostic aid in multiple sclerosis. kFLC Index seems to be more accurate parameter respect the determination of oligoclonal immunoglobulin bands (OCBs). We recalculate the K Index sensitivity and specificity respect the precedent published result. Two patients previously diagnosed with leukoencephalopathy have gone to group 3 as confirmed the diagnosis of MS. These new data reinforce even more the use of the k Index to diagnose MS in comparison to classical methods and to the reference method, the OCBs.

Immunoglobulin M oligoclonal bands: biomarker of targetable inflammation in primary progressive multiple sclerosis.

To identify a biomarker distinguishing patients who, despite a primary progressive multiple sclerosis (PPMS) clinical course, may nonetheless benefit from immune therapy. The presence or absence of both immunoglobulin (Ig) G and IgM oligoclonal bands (OCB) was blindly examined in paired cerebrospinal fluid (CSF) and serum samples from a large PPMS patient cohort, and related to clinical and imaging evidence of focal inflammatory disease activity. Using both cross-sectional samples and serial sampling in a subgroup of patients followed prospectively as part of the placebo-controlled OLYMPUS study of rituximab in PPMS, we found that the presence of CSF-restricted IgM OCB (but not of IgG OCB) is associated with an active inflammatory disease phenotype in PPMS patients. This finding was confirmed in an independent, multicenter validation cohort. The presence of CSF IgM OCB may be a biomarker for a subset of PPMS patients with more active inflammatory disease, who may benefit from immune-directed treatments.

Multiple sclerosis patients lacking oligoclonal bands in the cerebrospinal fluid have less global and regional brain atrophy

To investigate whether multiple sclerosis (MS) patients with and without cerebrospinal fluid (CSF) oligoclonal immunoglobulin G bands (OCB) differ in brain atrophy. Twenty-eight OCB-negative and thirty-five OCB-positive patients were included. Larger volumes of total CSF and white matter (WM) lesions; smaller gray matter (GM) volume in the basal ganglia, diencephalon, cerebellum, and hippocampus; and smaller WM volume in corpus callosum, periventricular-deep WM, brainstem, and cerebellum, were observed in OCB-positives. OCB-negative patients, known to differ genetically from OCB-positives, are characterized by less global and regional brain atrophy. This finding supports the notion that OCB-negative MS patients may represent a clinically relevant MS subgroup.

Clinically isolated syndrome manifested as acute vestibular syndrome: Bedside neuro-otological examination and suppression of transient evoked otoacoustic emissions in the differential diagnosis

A case of a 34-year old woman with acute vestibular syndrome caused by a demyelinating lesion in the root entry zone of the 8th cranial nerve is presented. Neuro-otological bedside examination and suppression of transient evoked otoacoustic emissions provided objective clinical evidence of a retrolabyrinthine lesion. Magnetic resonance imaging and the presence of oligoclonal IgG bands in cerebrospinal fluid analysis established the diagnosis of clinically isolated syndrome. This case report highlights the clinical information provided by the neuro-otologist in the differential diagnosis of the acute vestibular syndrome and the diagnosis of possible multiple sclerosis.

Optimization of supervised self-organizing maps with genetic algorithms for classification electrophoretic profiles

&lt;p&gt;Standard electrophoresis methods were used in the classification of analyzed proteins in cerebrospinal fluid from patients with multiple sclerosis. Disc electrophoresis was carried out for detection of oligoclonal IgG bands in cerebrospinal fluid on polyacrylamide gel, mainly with multiple sclerosis and other central nervous system dysfunctions. ImageMaster 1D Elite and GelPro specialized software packages were used for fast accurate image and gel analysis. The classification model was based on supervised self-organizing maps. In order to perform the modeling in automated manner genetic algorithms were used. Using this approach and a data set composed of 69 samples we were able to develop models based on supervised self-organizing maps which were able to correctly classify 83 % of the samples in the data set used for external validation.&lt;/p&gt;

Genetic and infectious profiles influence cerebrospinal fluid IgG abnormality in Japanese multiple sclerosis patients.

BackgroundAbnormal intrathecal synthesis of IgG, reflected by cerebrospinal fluid (CSF) oligoclonal IgG bands (OBs) and increased IgG index, is much less frequently observed in Japanese multiple sclerosis (MS) cohorts compared with Western cohorts. We aimed to clarify whether genetic and common infectious backgrounds influence CSF IgG abnormality in Japanese MS patients.MethodologyWe analyzed HLA-DRB1 alleles, and IgG antibodies against Chlamydia pneumoniae, Helicobacter pylori, Epstein-Barr virus nuclear antigen (EBNA), and varicella zoster virus (VZV) in 94 patients with MS and 367 unrelated healthy controls (HCs). We defined CSF IgG abnormality as the presence of CSF OBs and/or increased IgG index (>0.658).Principal FindingsCSF IgG abnormality was found in 59 of 94 (62.8%) MS patients. CSF IgG abnormality-positive patients had a significantly higher frequency of brain MRI lesions meeting the Barkhof criteria compared with abnormality-negative patients. Compared with HCs, CSF IgG abnormality-positive MS patients showed a significantly higher frequency of DRB1*1501, whereas CSF IgG abnormality-negative patients had a significantly higher frequency of DRB1*0405. CSF IgG abnormality-positive MS patients had a significantly higher frequency of anti-C. pneumoniae IgG antibodies compared with CSF IgG abnormality-negative MS patients, although there was no difference in the frequency of anti-C. pneumoniae IgG antibodies between HCs and total MS patients. Compared with HCs, anti-H. pylori IgG antibodies were detected significantly less frequently in the total MS patients, especially in CSF IgG abnormality-negative MS patients. The frequencies of antibodies against EBNA and VZV did not differ significantly among the groups.ConclusionsCSF IgG abnormality is associated with Western MS-like brain MRI features. DRB1*1501 and C. pneumoniae infection confer CSF IgG abnormality, while DRB1*0405 and H. pylori infection are positively and negatively associated with CSF IgG abnormality-negative MS, respectively, suggesting that genetic and environmental factors differentially contribute to MS susceptibility according to the CSF IgG abnormality status.

The presence of oligoclonal IgG bands in human CSF during the course of neurological diseases

The analysis of cerebrospinal fluid (CSF) is an important tool for the diagnosis of neurological diseases. However, there is limited knowledge about the representativity of a single oligoclonal band (OCB) analysis for a neurological disease during its clinical course. In this study, we analyzed the presence of OCB in the CSF of patients who underwent lumbar puncture more than once. We retrospectively analyzed anonymized data from serial 17,002 CSF analyses done in the CSF laboratory of the Department of Neurology, University Hospital Zurich. We included cases with documented diagnosis in whom OCB were determined more than once. We included 144 patients. The median time span between the first and second OCB analysis was 274 days (range, 1-3,533 days). The result of the second OCB analysis was identical in 109 cases, and different in 35 (24 %). Twenty-five patients acquired and ten patients lost OCB over time. Three of 24 MS patients did not show OCB at the first CSF analysis, but in the second. In the entire group, newly occurring OCB were often associated with new symptoms or occurred after the acute phase of CNS infectious diseases, supposedly as a consequence of the immune reaction. A loss of OCB was often associated with remissions from diseases, e.g., during effective treatment. In patients with neurological diseases, both initially positive and negative OCB results may change over time, which often parallels the clinical condition. Such variability must be taken into account for the interpretation of OCB results.

Associations of HLA DRB1 Alleles with Igg Oligoclonal Bands and Their Influence on Multiple Sclerosis Course and Disability Status

Background: Oligoclonal bands (OCB) may be associated with the genes of HLA complex, which allows to consider the possible interaction of genetic and immunological factors and its importance in the development and progression of multiple sclerosis (MS). Aim: To evaluate the importance of the associations between HLA DRB1 alleles and oligoclonal bands (OCB) in the multiple sclerosis (MS) patients disease course and disability. Metods: This was a prospective study of 120 patients with MS. HLA DRB1 alleles were genotyped using the polymerase chain reaction. Matched cerebrospinal fluid (CSF) and plasma samples were analysed using isoelectric focusing and IgG specific immunofixation to test for the presence of intrathecal specific OCB and compared directly with the serum samples. Results: HLA DRB1*08 allele be related to lower degree of disability, while the other HLA DRB1 alleles irrespective of the presence or absence of OCBs did not influence disability status. Oligoclonal bands were an indepedent and significant factor that influenced disability status irrespective of HLA DRB1* 04, *07, *08, *, *13, *15 and *16 alleles. Age at the onset of the first symptoms and duration of the disease were independent and significant factors for MS progression in all logistic regression models with each newly added HLA DRB1 allele. HLA DRB1*08 allele was related to 75% lower odds that relapsing remitting (RR) MS will change to a progressive course MS irrespective of the other factors investigated. In the model with *08 allele immunological factors had no impact on MS progression. Detection of OCBs in the CF was associated with the higher possibility of RR MS progression in all cases, except then the *08 allele was present. Conclusions: OCBs had an influence on disability status, while HLA DRB1*08 allele was significantly associated with lower possibility that RR MS will change to progressive course MS

Biomarkers for Multiple Sclerosis

Magnetic resonance imaging has been shown to be a powerful tool for diagnosing multiple sclerosis (MS) and evaluating surrogate markers of the disease activity. However, biomarkers may provide more accurate information regarding ongoing immune responses leading to demyelination and treatment effects in MS patients. Although serum biomarkers are easily accessible, they do not provide clear-cut results, whereas cerebrospinal fluid (CSF) biomarkers provide unequivocal information, although samples cannot be repeatedly obtained. For diagnosis, the presence of oligoclonal IgG bands remains important. In addition, measuring the levels of adhesion molecules, matrix metalloproteinase-9 and complement regulator factor H in the serum and evaluating the proportion of Th1/Th2 cells in the blood may be clinically feasible for monitoring the disease activity. In CSF samples, increased IL-8, IL-12, IL-17, CCL3, CCL5 and CXCL10 levels indicate active disease, and the flow cytometry findings of CSF cells can be used to detect increases in Th1 and CD4(+)CD25(+) cells during relapse. Biomarkers closely linked to the disease activity may be informative of the pathogenesis of MS, while those associated with tissue damage or repair may be targets of new treatment strategies. Establishing the latter will be a primary point of research in the near future.