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The 2010 McDonald criteria were developed to allow a more rapid diagnosis of relapsing-remitting multiple sclerosis (MS) by only one MRI of the brain. Although cerebrospinal fluid (CSF) is not a mandatory part of the latest criteria, the evidence of an intrathecal humoral immunoreaction in the form of oligoclonal bands (OCB) is crucial in the diagnostic workup. To date, the impact of the 2010 McDonald criteria on the prevalence of OCB has not been investigated. We retrospectively evaluated data of 325 patients with a clinical relapse suggestive of demyelination that were treated in a German university hospital between 2010 and 2015. One hundred thirty-six patients (42%) were diagnosed with MS and 189 patients with CIS when the criteria of 2010 were applied. The criteria of 2005 allowed only 70 patients (22%) to be designated as MS. In contrast, the prevalence of OCB was marginal affected in MS patients with 96% for the criteria of 2010 and 98.5% for the criteria of 2005. In conclusion, OCB are prevalent in most MS patients and reflect the chronic inflammatory nature of the disease. We recommend CSF examination to exclude alternative diagnoses and reevaluation of the diagnosis MS in patients with negative OCB. [ABSTRACT FROM AUTHOR]

Oligoclonal Ig bands (OCBs) of the cerebrospinal fluid are a hallmark of multiple sclerosis (MS), a disabling inflammatory disease of the central nervous system (CNS). OCBs are locally produced by clonally expanded antigen-experienced B cells and therefore are believed to hold an important clue to the pathogenesis. However, their target antigens have remained unknown, mainly because it was thus far not possible to isolate distinct OCBs against a background of polyclonal antibodies. To overcome this obstacle, we copurified disulfide-linked Ig heavy and light chains from distinct OCBs for concurrent analysis by mass spectrometry and aligned patientspecific peptides to corresponding transcriptome databases. This method revealed the full-length sequences of matching chains from distinct OCBs, allowing for antigen searches using recombinant OCB antibodies. As validation, we demonstrate that an OCB antibody from a patient with an infectious CNS disorder, neuroborreliosis, recognized a Borrelia protein. Next, we produced six recombinant antibodies from four MS patients and identified three different autoantigens. All of them are conformational epitopes of ubiquitous intracellular proteins not specific to brain tissue. Our findings indicate that the B-cell response in MS is heterogeneous and partly directed against intracellular autoantigens released during tissue destruction. In addition to helping elucidate the role of B cells in MS, our approach allows the identification of target antigens of OCB antibodies in other neuroinflammatory diseases and the production of therapeutic antibodies in infectious CNS diseases. [ABSTRACT FROM AUTHOR]

A 62-year-old diabetic man with prostate cancer first presented to our clinical laboratory in 2003 with a normal serum protein electrophoresis and immunofixation. In March 2009 he was diagnosed with an IgG κ myeloma. He underwent treatment and went into remission with the original paraprotein band being undetectable. Over the following 5 years, he developed oligoclonal bands and then eventually relapsed. Serum protein electrophoresis and immunofixation were inconclusive, however, isoelectrofocusing identified the oligoclonal pattern then the return of the original band, indicating relapse. This case illustrates the usefulness of an isoelectric focusing method to correctly determine clonality of small abnormal protein bands. It also highlights the need for appropriate commenting on reported results so that they are not confusing for clinicians. [ABSTRACT FROM AUTHOR]

Oligoclonal immunoglobulin G bands (OCBs) restricted to the cerebrospinal fluid indicate intrathecal inflammation. Using isoelectric focusing and immunoblotting, they are detected in about 95 % of patients with clinically definite multiple sclerosis (MS). To elucidate whether in the remaining 5 % OCBs are truly absent or alternatively missed due to insufficient sensitivity of the routine measurement, we employed a new, highly sensitive nanoscale method for OCB detection. Capillary isoelectric focusing followed by immunological detection served to analyze OCBs in 33 well-characterized OCB-negative and 10 OCB-positive MS patients as well as in 100 OCB-negative control patients with non-inflammatory neurological diseases and 30 OCB-positive control patients with inflammatory neurological diseases. We detected intrathecal immunoglobulin G production in 10 out of 33 MS patients (30 %), initially diagnosed as being OCB-negative, and in all 10 OCB-positive MS patients, but in only 3 out of 100 non-inflammatory neurological controls (3 %) and in 29 of 30 inflammatory neurological controls (97 %). At least about one-third of MS patients without intrathecal immunoglobulin G synthesis according to standard methods are OCB-positive. Advanced methods for OCB detection may increase the analytical sensitivity for detecting OCB in patients with MS who are OCB-negative according to current routine methods. [ABSTRACT FROM AUTHOR]

Despite advances in inducing remission in pediatric opsoclonus-myoclonus syndrome (OMS), relapse remains a challenge. By definition, relapse is not a characteristic of monophasic OMS, but occurs at any time in the course of multiphasic OMS. Due to variability and heterogeneity, patients are best approached and treated on a case-by-case basis, using precepts derived from clinical and scientific studies. Treatment of provocations, such as infection or immunotherapy tapering, is the short-term goal, but discovering unresolved neuroinflammation and re-configuring disease-modifying agents is crucial in the long-term. The working hypothesis is that much of the injury in OMS results from neuroinflammation involving dysregulated B cells, which may cause loss of tolerance and autoantibody production. Biomarkers of disease activity include cerebrospinal fluid (CSF) B cell frequency, oligoclonal bands (OCB), B cell attractants (CXCL13) and activating factors (BAFF). Measuring these markers comprises modern detection and characterization of neuroinflammation or verifies ‘no evidence of disease activity’. The decision making process is three-tiered: deciding if the relapse is bone fide, identifying its etiology, and formulating a therapeutic plan. Relapsing-remitting OMS is treatable, and combination multimodal/multi-mechanistic immunotherapy is improving the outcome. However, some patients progress to a refractory state with cognitive impairment and disability from failure to go into remission, multiple relapses, or more aggressive disease. This report provides new insights on underappreciated risks and pitfalls inherent in relapse, pro-active efforts to avoid progression, the need for early and sufficient treatment beyond corticosteroids and immunoglobulins, and utilization of disease activity biomarkers to identify high-risk patients and safely withdraw immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Kappa free light chains (KFLCs) have been proposed as a diagnostic biomarker in patients with clinically isolated syndrome (CIS) and multiple sclerosis (MS). Objective: The objective of this paper is to validate the diagnostic accuracy of intrathecal KFLC synthesis in a multicenter study. Methods: KFLCs were measured by nephelometry under blinded conditions in cerebrospinal fluid (CSF) and serum sample pairs of patients with CIS (n = 60), MS (n = 60) and other neurological diseases (n = 60) from four different MS centers. The upper normal limit for intrathecal KFLC concentrations depending on blood-CSF barrier function was previously calculated in a cohort of 420 control patients. Results: Diagnostic sensitivity of intrathecal KFLC synthesis, IgG synthesis according to Reiber, IgG index and oligoclonal bands (OCBs) was 95%, 72%, 73% and 93% in patients with MS and 82%, 47%, 43% and 72% in patients with CIS. Specificity of intrathecal KFLC synthesis was 95% and 98% for all other measures. Conclusion: These findings further support the diagnostic value of intrathecal KFLC synthesis in CIS and MS patients and demonstrate a valid, easier and rater-independent alternative to OCB detection. [ABSTRACT FROM AUTHOR]

Objective It has been suggested that autoantibodies may induce axonal damage in multiple sclerosis (MS). Optical coherence tomography (OCT) showed that thinning of peripapillary retinal nerve fiber layer (RNFL) and ganglion cell layer/inner plexiform (GCIPL) measurements reflect axonal loss in the disease. We investigated whether the intrathecal synthesis of lipid-specific oligoclonal IgM bands (LS-OCMB) associates with thinning of these structures in MS patients. Methods 58 consecutive MS patients and 70 age-matched healthy controls were assessed. LS-OCMB was studied in cerebrospinal fluid by isoelectric focusing and immunoblotting. RNFL and GCIPL imaging were quantified by spectral domain OCT. Results RNFL and GCIPL were significantly reduced in MS patients compared to controls (p < 0.01). RNFL thickness was further reduced in LS-OCMB positive MS patients compared to LS-OCMB negative MS subjects mainly in papillomacular bundle (p < 0.05), temporal and inferior quadrants (p < 0.05) and inferotemporal sector (p = 0.01). Conclusions The presence of LS-OCMB associates with increased retinal axonal loss in MS. This reinforces the relationship found between the intrathecal synthesis of IgM and the axonal damage observed in immunological and pathological studies even in normal-appearing white matter. OCT seems an optimal tool to monitor axonal damage in LS-OCMB positive patients, relevant for therapeutic decisions and quantification of the effects of new neuroprotective treatments [ABSTRACT FROM AUTHOR]

CSF oligoclonal bands (OCBs) in patients with clinically isolated syndromes (CIS) are a risk factor for clinically definite multiple sclerosis (CDMS). We aimed to address the relevance of the number of OCBs in the prognosis of CIS patients. 219 CIS patients were included in the study, and 42% of them developed the disease during follow-up (median: 5.04 years). Patients with a high number of CSF OCBs (third quartile, 8–12 OCBs) had 2.5-fold increase in CDMS risk, while no further increase in the HR of disease was observed for patients with more than 12 OCBs. The results did not change after adjustment for additional correlates of CDMS development. This association may be due to the epitope-spreading phenomenon and may reflect the stage of the disease at the time of the examination. [ABSTRACT FROM AUTHOR]

We assessed the frequency of cerebrospinal fluid (CSF) restricted oligoclonal IgG bands (IgG-OCB) in Portuguese multiple sclerosis (MS) patients and its relationship with outcome. Paired CSF/serum samples of 406 patients with neurological disorders were submitted to isoelectric focusing with immunodetection of IgG. Ninety-two patients had definite MS; non-MS cases were assembled in groups inflammatory/infectious diseases (ID, n=141) and other/controls (OD, n=173). We found in the MS group: mean duration, 38.9 months; clinically isolated syndromes, 24%; relapsing/remitting course (RR), 65%; in RR patients the mean EDSS was 2.1 and the mean index of progression was 0.31. Positive patterns significantly predominated in MS (82.6%; ID, 40.4%; OD, 3.5%). The sensitivity and the specificity of positive IgG-OCB for MS diagnosis was 82.6% and 79.9%, respectively. The sole statistically significant difference in the MS group was the lower progression index observed in negative cases. We conclude that the frequency of positive IgG-OCB patterns in our MS patients fits most values reported in the literature, and that negative results indicate benign disease.Analisamos a frequência de bandas oligoclonais (BOC) restritas ao líquido céfalo-raquidiano (LCR) em doentes portugueses com esclerose múltipla (EM) e sua relação com a clínica. Determinaram-se por focagem isoeléctrica e imunodetecção as BOC da IgG em pares de amostras LCR/soro de 406 doentes com diversas patologias neurológicas: 92 tinham EM definitiva; os casos "não-EM" agruparam-se em doenças inflamatórias/infecciosas (ID; n=141) e outras/controles (OD; n=173). O grupo EM apresentava duração média: 38,9 meses; síndromes clinicamente isolados (CIS), 24%; formas surto/remissão (RR), 65%, nas quais se encontrou EDSS e índice de progressão médios de 2,1 e 0,31, respectivamente. O perfil positivo predominava significativamente na EM (82,6%; ID, 40,4%; OD, 3,5%), cuja sensibilidade e especificidade neste diagnóstico foi 82% e 79,9%, respectivamente. A única diferença estatisticamente significativa no grupo EM foi o menor índice de progressão nos casos negativos. Em conclusão, a frequência de BOC positivas nos nossos doentes EM enquadrou-se nos valores da literatura, e a sua negatividade indicou evolução benigna.

We analyzed the genetic recombination pattern of the T-cell receptor beta-chain gene (TCR-beta) in order to identify clonal expansion of T-lymphocytes in 17 human T-lymphotropic virus type I (HTLV-I)-positive healthy carriers, 7 of them with abnormal features in the peripheral blood lymphocytes. Monoclonal or oligoclonal expansion of T-cells was detected in 5 of 7 HTLV-I-positive patients with abnormal lymphocytes and unconfirmed diagnosis by using PCR amplification of segments of TCR-beta gene, in a set of reactions that target 102 different variable (V) segments, covering all members of the 24 V families available in the gene bank, including the more recently identified segments of the Vbeta-5 and Vbeta-8 family and the two diversity beta segments. Southern blots, the gold standard method to detect T-lymphocyte clonality, were negative for all of these 7 patients, what highlights the low sensitivity of this method that requires a large amount of very high quality DNA. To evaluate the performance of PCR in the detection of clonality we also analyzed 18 leukemia patients, all of whom tested positive. Clonal expansion was not detected in any of the negative controls or healthy carriers without abnormal lymphocytes. In conclusion, PCR amplification of segments of rearranged TCR-beta is reliable and highly suitable for the detection of small populations of clonal T-cells in asymptomatic HTLV-I carriers who present abnormal peripheral blood lymphocytes providing an additional instrument for following up these patients with potentially higher risk of leukemia.

Oligoclonal bands (OCB) can be detected in a significant percentage (90%) of patients with multiple sclerosis (MS), however, a much lower percentage has been reported in some studies, mainly from oriental countries. On the other hand, OCB have been detected in other neurological disorders (OND), even in diseases without any definite evidence for inflammation in CSF such as myasthenia gravis. This study was undertaken to evaluate the sensitivity and specificity of OCB detection in cerebrospinal fluid (CSF) in diagnosis of MS and to compare the clinical history of patients with and without OCB. CSF and serum of 80 patients, 40 with the diagnosis of MS and 40 with OND, were collected and analyzed for presence of OCB, using SDS-PAGE method. OCB were found in CSF in 28 (70%) of MS patients and in 8 (20%) of OND group. There was a significant statistical correlation between detection of OCB in CSF and MS diagnosis (P

Locally produced oligoclonal IgG bands (OCB) are present in the cerebrospinal fluid (CSF) of 95% patients with multiple sclerosis (MS)[2,3]. The most sensitive method for the detection of OCB is isoelectric focusing (IEF) [1]. Occasional patients with clinically definite MS lack evidence for intrathecal IgG synthesis [2,9]. This study was designed to compare brain magnetic resonance imagining (MRI) findings between CSF OCB positive and negative MS patients. The study comprised 22 OB negative patients with clinically definite MS and 22 OCB positive controls matched for age, disease duration, activity and course of MS. In the both groups clinical assessment was performed by using Expanded Disability Status Scale (EDSS) score. T2 weighted MRI of the brain was performed on a Siemens Magnetom (1.0 T). Lesions were countred and sized for 15 anatomically defined locations:7 periventricular (PV) and 8 non-periventricular (NPV) regions. An arbitrary scoring system weighted for lesions size was used to estimate total and regional lesions loads: a)1 point was given for each lesion with a diameter 1-5 mm, b) 2 points for one lesion with a diameter 6-10 mm, c) 3 points for one over 10 mm, and confluent lesions scored one extra point [16]. Atrophy were scored as follows: 0-normal size, 1-mild atrophy, 2-moderate atrophy and 3-severe atrophy. Mean score of total brain MRI loads was lower in OCB negative than in OCB positive MS patients (44 vs. 50) but the difference was not statistically significant. Mean periventricular (32 vs. 23) non-periventricular (26 vs. 19) and infratentorial (11 vs. 9) scores were higher in OCB positive MS group in comparison with OCB negative patients but non-significant (figure 1). There was no correlation between EDSS score and total MRI lesions load in OCB negative MS patients, while in OCB positive group we detected significant correlation between EDSS score and total MRI lesions load (p=0.026) (figure 2). The results of this study demonstrate that by using conventional brain MRI the extent end severity of the pathological process seems to be similar in OCB negative and OCB postive MS patients. On the other hand, we found statistically significant correlation between brain MRI total lesion load and EDSS in the OCB positive MS patients, while this correlation was not detected in OCB negative MS patients. Differences in brain MRI findings between OCB positive nad OCB negative MS patients have been already analyzed [9,12]. In the first, Zeman et al. reported that OCB negative MS patients have lower total MRI brain lesion loads in comparison to OCB positive group, but the differences was not statistically significant [9]. In accordance with these findings Fukazawa et al. also failed to show differences in the distribution, extent shape and number of brain MRI lesions between OCB positive and negative MS patients. [12]. On the other hand, it has been demonstrated that the rate of intrathecal IgG synthesis apparently correlates with plaque volume in the brain, as demonstrated on MRI, in MS patients [17]. However, our results along with those from two above-mentioned previous studies do not support this notion. In conclusion, trend towards lesser MRI lesion load and lack of its correlation with EDSS in OCB negative MS patients, warrants further investigations with new MRI techniques (magnetic resonance spectroscopy and magnetisation transfer), including the thorough exploration of normal-appearing white matter, in OCB negative MS patients.

We analyzed cerebrospinal fluid (CSF) and blood serum from 55 patients with neurocysticercosis (NC) at different clinical stages. According to inflammatory activity in the CSF, three stages were identified: (1) reactive, when there was at least an increase in the number of cells; (2) weakly reactive, when significant alterations were found in the CSF, including an increase in gamma globulins, albeit without hypercytosis; (3) non-reactive, when there was neither hypercytosis nor increase in gamma globulins. Nineteen patients had the reactive form; 18 had the weakly reactive form; 18 displayed the non-reactive form. Local immunoproduction was intense in the reactive group, moderate in the weakly reactive group, and absent in the non-reactive group. The specific antibody index was raised in approximately 2/3 of patients with the reactive form, 2/3 in those with the weakly reactive form, and 1/3 in those with the non-reactive form. In conclusion: (1) the classical CSF syndrome in NC can present both in complete and partial modes; (2) local immunoproduction can occur in weakly reactive forms; (3) a raised specific antibody index can occur in the absence of an inflammatory reaction in the CSF.

Cholesterol is essential for myelin formation, but may also modulate mechanisms involved in adaptive immune responses. It is unclear whether lack of remyelination in multiple sclerosis (MS) results from an insufficient capacity of oligodendrocyte precursor cells to differentiate or from cholesterol insufficiency. Several studies have assessed the potential association of lipid profile and its metabolism with demyelination, disability, and disease progression. The aim of the present study was to measure cholesterol levels in plasma and cerebrospinal fluid (CSF) of patients with relapsing remitting MS (RRMS) or with clinically isolated syndrome (CIS), and to investigate whether there is an association between cholesterol levels and disease characteristics. Sixty-two patients with CIS and 46 patients with RRMS were included in the study. All patients had low EDSS and were medication-free at assessment. Forty-eight subjects within the same age range served as controls. Cholesterol concentrations were measured in plasma and in CSF by the same enzymatic – colorimetric method, and were related to clinical status, disease activity in magnetic resonance imaging (MRI) and presence of oligoclonal bands in CSF (OBs). Significantly lower levels of plasma and CSF cholesterol were found in patients compared to controls. Patients with OBs showed significantly lower levels of CSF cholesterol but not plasma cholesterol compared to OBs-negative patients. A positive correlation of plasma cholesterol with age and of CSF cholesterol with EDSS was found. Our results suggest that low CSF cholesterol in MS patients with positive OBs might reflect extensive demyelination and a more aggressive disease course associated with an increased humoral immune response against membrane components. • Lack of remyelination in multiple sclerosis (MS) may result from cholesterol insufficiency in the cerebrospinal fluid (CSF) • MS patients show lower plasma and CSF cholesterol levels compared to controls. • Lower CSF cholesterol levels are associated with presence of oligoclonal bands in CSF. • Low CSF cholesterol in MS patients with positive CSF oligoclonal bands might reflect more extensive demyelination [ABSTRACT FROM AUTHOR]

Background: Diagnosis of multiple sclerosis (MS) is established on criteria according to clinical and radiological manifestation. Cerebrospinal fluid (CSF) analysis is an important part of differential diagnosis of MS and other inflammatory processes in the central nervous system (CNS)., Methods: In total, 242 CSF samples were collected from patients undergoing differential MS diagnosis because of the presence of T2-hyperintensive lesions on brain MRI. The non-MS patients were subdivided into systemic inflammatory diseases with CNS involvement (SID) or cerebrovascular diseases (CVD) or other non-inflammatory diseases (NID). All samples were analyzed for the presence of oligoclonal bands and ELISA was performed for detection of: INF gamma, IL-6, neurofilaments light chain (NF-L), GFAP, CHI3L1, CXCL13, and osteopontin., Results: The level of IL-6 ( p = 0.024), osteopontin ( p = 0.0002), and NF-L ( p = 0.002) was significantly different among groups. IL-6 ( p = 0.0350) and NF-L ( p = 0.0015) level was significantly higher in SID compared to NID patients. A significantly higher level of osteopontin ( p = 0.00026) and NF-L ( p = 0.002) in MS compared to NID population was noted. ROC analysis found weak diagnostic power for osteopontin and NFL-L., Conclusions: The classical and non-standard markers of inflammatory process and neurodegeneration do not allow for sufficient differentiation between MS and non-MS inflammatory CNS disorders. Weak diagnostic power observed for the osteopontin and NF-L needs to be further investigated.

Multiple sclerosis is a chronic neurological disease characterized by inflammation and degeneration within the central nervous system. Over the course of the disease, most MS patients successively accumulate inflammatory lesions, axonal damage, and diffuse CNS pathology, along with an increasing degree of motor disability. While the pharmacological approach to MS targets inflammation to decrease relapse rates and relieve symptoms, disease-modifying therapy and immunosuppressive medications may not prevent the accumulation of pathology in most patients leading to long-term motor disability. This has been met with recent interest in promoting plasticity-guided concepts, enhanced by neurophysiological and neuroimaging approaches to address the preservation of motor function., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Multiple sclerosis (MS) is a chronic autoimmune-mediated demyelinating disease of the central nervous system (CNS) that is usually associated with varying degrees of progressive disability. Chitinase-3-like protein-1 (CHI3L1) has attracted growing attention as a marker of ongoing inflammation and oncogenic transformation. The aim of this work was to assess the diagnostic accuracy of CHI3L1 versus IgG oligoclonal bands (OCBs) in the cerebrospinal fluid (CSF) of newly diagnosed relapsing remitting MS (RRMS) patients to throw light on a new simpler non subjective potential diagnostic marker in MS. This cross-sectional study of MS patients was carried at Ain Shams University Hospitals during the period from January 2021 till January 2022. Subjects included in this study were 40 patients diagnosed as having RRMS, based on their magnetic resonance imaging (MRI) findings, clinical presentation and according to the revised McDonald criteria 2017. The group included 10 males and 30 females; their ages ranged from 20 to 45 years. We found a significant correlation between CSF CHI3L1 levels and presence of oligoclonal bands (p=0.001), and that a cut off value of 30 ng/ml could be used for diagnosis of MS with sensitivity 84.85% and specificity 85.71%. A significant association was also found between CHI3L1 levels in CSF and Expanded Disability Status Scale (EDSS) score (p=0.002). We concluded that there were high levels of CHI3L1 in the CSF of MS patients and there was a significant correlation between CHI3L1 and oligoclonal bands and that CHI3L1 may be considered a promising diagnostic marker of MS., (Copyright© by the Egyptian Association of Immunologists.)

Background: More than 100 common variants underlying multiple sclerosis (MS) susceptibility have been identified, but their effect on disease phenotype is still largely unknown. Objective: The objective of this paper is to assess whether the cumulative genetic risk score of currently known susceptibility variants affects clinical presentation. Methods: A cumulative genetic risk score was based on four human leukocyte antigen (HLA) and 106 non-HLA risk loci genotyped or imputed in 842 Belgian MS patients and 321 controls. Non-parametric analyses were applied. Results: An increased genetic risk is observed for MS patients, including subsets such as oligoclonal band-negative and primary progressive MS patients, compared to controls. Within the patient group, a stronger association between HLA risk variants and the presence of oligoclonal bands, an increased immunoglobulin G (IgG) index and female gender was apparent. Results suggest an association between a higher accumulation of non-HLA risk variants and increased relapse rate as well as shorter relapse-free intervals after disease onset. Conclusion: MS patients display a significantly increased genetic risk compared to controls, irrespective of disease course or presence of oligoclonal bands. Whereas the cumulative burden of non-HLA risk variants appears to be reflected in the relapses of MS patients, the HLA region influences intrathecal IgG levels. [ABSTRACT FROM AUTHOR]

Objectives: The pathogenesis of idiopathic intracranial hypertension (IIH) is currently unknown and there are speculations about the contribution of some immunologic factors. The aim of this study is to investigate the presence of oligoclonal bands (OCBs) and cerebrospinal fluid (CSF) and/or serum cytokine levels in patients with IIH.Methods: Patients fulfilling revised diagnostic criteria for IIH were included. Their demographic, clinical, ophthalmologic and laboratory features were examined. Serum and CSF samples were detected by isoelectric focusing and immunoblotting for OCBs. The samples of IIH patients and control groups were investigated by ELISA for cytokine levels.Results: We detected OCBs in eight (30.77%) patients diagnosed with IIH. There were no other obvious clinical and laboratory differences of IIH profiles between the patients with and without OCBs, but frequency of vision loss was significantly higher in the group with OCBs in comparison to OCB negatives (p = 0.038). Patients with IIH had highly elevated TNF-α, IFN-γ, IL-4, IL-10, IL-12, IL-17 in their sera compared to patients with multiple sclerosis (MS) and healthy controls. Furthermore, all cytokines except TNF-α in the CSF were found significantly higher in IIH patients compared to MS controls.Conclusion: The presence of OCBs and elevated cytokine levels in IIH patients may support an immunologic background in the pathophysiological pathway of this disorder. [ABSTRACT FROM AUTHOR]

The presence of cerebrospinal fluid oligoclonal bands (CSF-OCB) in Caucasian patients with multiple sclerosis (MS) is supportive of diagnosis, though the relation with patients' clinical and specifically cognitive features has never been established or thoroughly examined. Thus, we investigated the clinical and for the first time the cognitive profile of MS patients in relation to CSF-OCB. We studied 108 patients with and without OCB and recorded demographic characteristics and detailed clinical data. A comprehensive neuropsychological battery covering different cognitive domains (attention/processing speed, memory, perception/constructions, reasoning, executive functions) was administered to MS patients and 142 demographically related healthy controls (HC). We did not find any significant differences between patients with and without OCB on demographic and clinical parameters (p > 0.05), including subtype and brain neuroimaging findings. Results revealed significantly higher cognitive scores in HC compared to both OCB subgroups, with more widespread cognitive changes in patients with OCB. Analysis between OCB subgroups showed significantly worse performance in patients with OCB on visual memory (Rey's complex figure test-recall; p = 0.006). Concluding, the presence of CSF-OCB in our MS patients tends to be related to more widespread cognitive changes, specifically worse visual memory. Future longitudinal studies in different populations are warranted to better clarify the clinical and cognitive characteristics related to CSF-OCB which could serve as early biomarker in disease monitoring. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is associated with Epstein–Barr virus (EBV) infection. A characteristic feature of MS is an intrathecal synthesis of immunoglobulin (Ig)G. In 90 patients with clinically isolated syndromes/early relapsing–remitting MS, serum antibodies to Epstein–Barr nuclear antigen-1, but not to EBV viral capsid antigen, rubella, or varicella zoster virus, were higher ( p = 0.03) in those with than those without a calculated intrathecal IgG synthesis > 0% and correlated with the percentage (r = 0.27, p = 0.009) and concentration (r = 0.27, p = 0.012) of intrathecally produced IgG. These findings suggest a link between EBV infection and the events leading to intrathecal IgG synthesis in patients with MS. [ABSTRACT FROM AUTHOR]

Background: Recent findings have shown a correlation between the intrathecal IgG index and variants at the immunoglobulin heavy chain (IGHC) locus in patients with multiple sclerosis (MS). Objectives: The objective of this paper is to analyse the association of the locus with MS susceptibility and its relationship with intrathecal immunoglobulin (Ig) parameters. Methods: We genotyped the rs11621145 variant, located at the IGHC locus, in 2726 patients with MS and 2133 healthy controls. Associations of intrathecal IgG and IgM indexes with rs11621145 were analysed by linear regression analysis in 538 MS patients. Results: We found that rs11621145 showed statistically significant evidence for association with susceptibility to MS (odds ratio = 0.69, p = 1.053E-09), though validation of this result in additional cohorts would be desirable. We confirmed the association between the IgG index and the rs11621145 (p = 6.85E-07, Beta = 0.207). Furthermore, rs11621145 was inversely correlated with IgM index (p = 7.24E-04, Beta = -0.277), and therefore marks a decreased likelihood of presenting IgM oligoclonal bands (odds ratio = 0.38, p = 2.35E-06). Conclusions: Our results suggest that the polymorphism of the IGHC locus could be altering the switching of the Ig isotype in B cells and it may be interfering with T-dependent and T-independent antibody responses. [ABSTRACT FROM AUTHOR]

In the pathogenesis of multiple sclerosis (MS), B cell/antibody-related mechanisms have recently received attention. To investigate the role of autoantibody in MS, we performed SEREX which can identify autoantibody cyclopedically. We identified serum antibodies against cytoskeletal protein talin1, and the levels of whom were remarkably higher in 39 MS than 43 normal controls ( P < 0.01) and 35 disease controls ( P = 0.06), and in MS patients without oligoclonal bands than ones with them. Moreover, we found negative-correlations between serum anti-talin1 antibody and IgG index in MS ( P = 0.03). Anti-talin1 antibody exists in MS patients' sera, which may have some protective factor. [ABSTRACT FROM AUTHOR]

Objectives Presence of oligoclonal bands ( OCB) in cerebrospinal fluid ( CSF) is a diagnostic hallmark of multiple sclerosis ( MS). However, up to 10% of patients were OCB negative in routine laboratory tests. The aim of this study was to determine whether there is at least an oligoclonal restriction of intrathecal antibody synthesis against measles, rubella and/or varicella zoster virus ( MRZ-specific OCB) in CSF from oligoclonal bands-negative patients with MS. Methods CSF and serum samples from 17 well-defined OCB-negative patients with MS were analysed for MRZ-specific OCB. We performed isoelectric focusing ( IEF) combined with affinity blotting using viral antigens, detection with a highly sensitive chemiluminescence technique and recording with X-ray films. Controls included 18 OCB-positive patients with MS and 11 patients with pseudotumor cerebri ( PTC). Results Exclusive or predominant MRZ-specific OCB in CSF against at least one virus species were present in 8 of 17 patients with MS (47.1%; P = 0.0422), suggesting an oligoclonal intrathecal immune response, although OCB of total IgG were absent. Only a very weak oligoclonal reaction against varicella zoster virus in CSF from one of the PTC controls was detectable. Thirteen of 18 (72.2%; P = 0.0013) OCB-positive patients with MS showed also MRZ-specific oligoclonal bands against at least 1 neurotropic virus in CSF. Conclusions MRZ-specific OCB argue for existence of a chronic intrathecal immune reaction also in routine laboratory- OCB-negative patients with MS. This phenomenon reflects oligoclonal restriction of the humoral immunoreaction as well as polyspecific intrathecal antibody synthesis, which are both characteristics in the chronic inflammatory process of MS. [ABSTRACT FROM AUTHOR]

Retrospective studies show that natalizumab modifies oligoclonal immunoglobulin (IgG) bands (OCBs) in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. In this study, we prospectively analyzed both serum and CSF samples from 24 MS patients, before and after 2 years of natalizumab-based therapy. Our results showed complete (55%) or partial (27%) disappearance of the OCBs in CSF samples that were taken after 2 years of therapy. Intrathecal IgG production, represented by the IgG index and IgGLoc, was also quantitatively reduced. Our data showed that natalizumab substantially modulates both intrathecal polyclonal and oligoclonal IgG production: This effect was much more potent than was previously reported. [ABSTRACT FROM AUTHOR]

Central nervous system methotrexate-associated lymphoproliferative disorder (CNS-MTX-LPD) is rare, but its spontaneous regression has been observed in some patients after withdrawal of agents. We herein report three cases of primary CNS-MTX-LPD that received oral MTX for rheumatoid arthritis. Epstein-Barr virus and oligoclonal bands (OCBs) were positive, while proton magnetic resonance spectroscopy ( 1 H-MRS) showed an elevated lipid peak and slightly elevated choline/N-acetylaspartate ratio in common. After MTX withdrawal, brain lesions showed spontaneous regression in all cases. Our patient's 1 H-MRS findings and OCBs may reflect a non-monoclonal lymphoproliferative histology as benign-type lesions in CNS-MTX-LPD.