FURTHER STUDIES ON THE GAMMA GLOBULIN CONTENT OF CEREBROSPINAL FLUID IN MULTIPLE SCLEROSIS AND OTHER NEUROLOGICAL DISEASES

1954 ◽  
Vol 58 (5) ◽  
pp. 613-624 ◽  
Author(s):  
Melvin D. Yahr ◽  
Sidney S. Goldensohn ◽  
Elvin A. Kabat
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Gamma Globulin ◽  
Neurological Diseases

(University of Pennsylvania Case Conference): oligoclonal immunoglobulins in cerebrospinal fluid in multiple sclerosis.

1980 ◽  
Vol 26 (9) ◽  
pp. 1340-1345 ◽  
Author(s):  
A A Keshgegian ◽  
J Coblentz ◽  
R P Lisak
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Gamma Globulin ◽  
Neurological Diseases ◽  
Broad Band ◽  
Lymphoproliferative Disorders ◽  
University Of Pennsylvania ◽  
Case Conference ◽  
Monoclonal Immunoglobulins ◽  
The Many

Abstract In the normal state, immunoglobulins are polyclonal. They migrate as a broad band on electrophoresis, reflecting the diversity of immunoglobulin species secreted by the many clones of immunoglobulin-producing cells. In lymphoproliferative disorders, monoclonal immunoglobulins are often found, migrating as electrophoretically homogeneous bands, reflecting the large amount of a single immunoglobulin being secreted by the single proliferating neoplastic clone. In certain neurological diseases, such as multiple sclerosis, the cerebrospinal fluid (CSF)2 often exhibits an oligoclonal immunoglobulin pattern consisting of several electrophoretically homogeneous bands in the gamma-globulin regin (Figure 1). We present two cases of neurological disease with an oligoclonal immunoglobulin pattern in the CSF electropherogram. In the discussion we consider the definition, etiology, and pathogenesis of multiple sclerosis, and laboratory tests that are useful in multiple sclerosis, emphasizing methods for the demonstration and interpretation of an oligoclonal immunoglobulin pattern.

Multiple sclerosis risk genotypes correlate with an elevated cerebrospinal fluid level of the suggested prognostic marker CXCL13

2012 ◽  
Vol 19 (7) ◽  
pp. 863-870 ◽  
Author(s):  
M Lindén ◽  
M Khademi ◽  
I Lima Bomfim ◽  
F Piehl ◽  
M Jagodic ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Neurological Diseases ◽  
Severe Disease ◽  
Human Leukocyte ◽  
Disease Course ◽  
Nucleotide Polymorphisms ◽  
Treatment Protocols ◽  
Tnfaip3 Gene ◽  
Cerebrospinal Fluid Level

Background: The mechanisms of multiple sclerosis (MS) pathogenesis are still largely unknown. The heterogeneity of disease manifestations make the prediction of prognosis and choice of appropriate treatment protocols challenging. Recently, increased cerebrospinal fluid (CSF) levels of the B-cell chemokine CXCL13 was proposed as a possible marker for a more severe disease course and conversion from clinically isolated syndrome (CIS) to relapsing–remitting MS (RRMS). Objective: To investigate whether there are genetic susceptibility variants in MS that correlate with the levels of CXCL13 present in the CSF of MS patients. Methods: We genotyped the human leukocyte antigens HLA-DRB1 and HLA-A, plus a panel of single nucleotide polymorphisms (SNPs) that have been associated with susceptibility to MS and then correlated the genotypes with the levels of CXCL13, as measured with ELISA in the CSF of a total of 663 patients with MS, CIS, other neurological diseases (OND) or OND with an inflammatory component (iOND). Results: Presence of the HLA-DRB1*15 and the MS risk genotypes for SNPs in the RGS1, IRF5 and OLIG3/TNFAIP3 gene regions correlated significantly with increased levels of CXCL13. Conclusion: Our results pointed towards a genetic predisposition for increased CXCL13 levels, which in MS patients correlates with the severity of the disease course. These findings encourage further investigation and replication, in an independent patient cohort.

The contribute of cerebrospinal fluid free light-chain assay in the diagnosis of multiple sclerosis and other neurological diseases in an Italian multicenter study

2021 ◽  
pp. 135245852110641
Author(s):  
Gaetano Bernardi ◽  
Tiziana Biagioli ◽  
Paola Malpassi ◽  
Teresa De Michele ◽  
Domizia Vecchio ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Neurological Disorders ◽  
Operating Characteristic ◽  
Neurological Diseases ◽  
Characteristic Curve ◽  
Oligoclonal Bands ◽  
Free Light Chains ◽  
Complementary Information ◽  
Combined Use

Background: Cerebrospinal fluid (CSF) free light chains (FLCs) can be an alternative assay to oligoclonal bands (OCBs) in inflammatory neurological disorders, but threshold has no consensus. Objective: To assess the diagnostic accuracy of CSF FLCs in multiple sclerosis (MS) and other neurological diseases. Methods: A total of 406 patients from five Italian centers. FLCs were measured in CSF and serum using Freelite MX assays on Optilite. Results: A total of 171 patients were diagnosed as MS, 154 non-inflammatory neurological diseases, 48 inflammatory central nervous system (CNS) diseases, and 33 peripheral neurological diseases. Both kFLC and λFLC indices were significantly higher in patients with MS compared to other groups ( p < 0.0001). The kFLC index ⩾ 6.4 is comparable to OCB for MS diagnosis (area under the receiver operating characteristic curve (AUC) = 0.876; sensitivity 83.6% vs 84.2%; specificity 88.5% vs 90.6%). λFLC index ⩾ 5 showed an AUC of 0.616, sensitivity of 33.3% and specificity of 90.6%. In all, 12/27 (44.4%) MS patients with negative OCB had kFLC index ⩾ 6.4. Interestingly, 37.5% of 24 patients with a single CSF IgG band showed high kFLC index and 12.5% positive λFLC index. Conclusion: Our findings support the diagnostic utility of FLC indices in MS and other CNS inflammatory disorders, suggesting a combined use of FLC and OCB to help clinicians with complementary information.

scholarly journals Double Filtration Plasmapheresis Treatment of Refractory Multiple Sclerosis Relapsed on Fingolimod: A Case Report

2020 ◽  
Vol 10 (21) ◽  
pp. 7404
Author(s):  
Roberto De Masi ◽  
Stefania Orlando ◽  
Salvatore Accoto
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Improvement ◽  
Gamma Globulin ◽  
Neurological Diseases ◽  
Methyl Prednisolone ◽  
Double Filtration Plasmapheresis ◽  
First Case ◽  
Double Filtration ◽  
Steroid Refractory ◽  
Inflammatory Effect

Double filtration plasmapheresis (DFPP) is an emerging semi-selective apheretic method for treating immuno-mediated neurological diseases. Here we report the first case of steroid-refractory relapsed multiple sclerosis (MS) on Fingolimod (FTY), treated effectively by this technique, in a 37-year-old woman. This condition is thought to be caused by soluble inflammatory species, but its demyelinating pattern is unknown; moreover, despite megadoses of intravenous 6-methyl prednisolone, it induces severe neurological deterioration, but dramatically responded to DFPP in our patient. The clinical improvement was driven by a strong DFPP-induced anti-inflammatory effect, with significant reduction of C3/C4 components, total gamma globulin concentrations (IgG), and gamma-fibrinogen (FGG), resulting in a brain pseudoatrophy phenomenon. Our findings are: first, the steroid-refractory relapsed MS on FTY, however serious, can be treated with DFPP; second, given the good clinical improvement due to the DFPP-induced neuroinflammatory components removal, this clinical condition can be associated with a Lucchinetti pattern II of demyelination.

scholarly journals Inflammation-related plasma and CSF biomarkers for multiple sclerosis

2020 ◽  
Vol 117 (23) ◽  
pp. 12952-12960 ◽  
Author(s):  
Jesse Huang ◽  
Mohsen Khademi ◽  
Lars Fugger ◽  
Örjan Lindhe ◽  
Lenka Novakova ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Neurological Diseases ◽  
Area Under The Curve ◽  
Csf Biomarkers ◽  
Healthy Controls ◽  
Protein Biomarkers ◽  
Neurofilament Light Chain ◽  
Diagnostic Efficacy ◽  
Neurofilament Light

Effective biomarkers for multiple sclerosis diagnosis, assessment of prognosis, and treatment responses, in particular those measurable in blood, are largely lacking. We have investigated a broad set of protein biomarkers in cerebrospinal fluid (CSF) and plasma using a highly sensitive proteomic immunoassay. Cases from two independent cohorts were compared with healthy controls and patients with other neurological diseases. We identified and replicated 10 cerebrospinal fluid proteins including IL-12B, CD5, MIP-1a, and CXCL9 which had a combined diagnostic efficacy similar to immunoglobulin G (IgG) index and neurofilament light chain (area under the curve [AUC] = 0.95). Two plasma proteins, OSM and HGF, were also associated with multiple sclerosis in comparison to healthy controls. Sensitivity and specificity of combined CSF and plasma markers for multiple sclerosis were 85.7% and 73.5%, respectively. In the discovery cohort, eotaxin-1 (CCL11) was associated with disease duration particularly in patients who had secondary progressive disease (PCSF< 4 × 10−5,Pplasma< 4 × 10−5), and plasma CCL20 was associated with disease severity (P= 4 × 10−5), although both require further validation. Treatment with natalizumab and fingolimod showed different compartmental changes in protein levels of CSF and peripheral blood, respectively, including many disease-associated markers (e.g., IL12B, CD5) showing potential application for both diagnosing disease and monitoring treatment efficacy. We report a number of multiple sclerosis biomarkers in CSF and plasma for early disease detection and potential indicators for disease activity. Of particular importance is the set of markers discovered in blood, where validated biomarkers are lacking.

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