Cerebrospinal fluid B-cell phenotype and intrathecal IgG synthesis suggest a local on-going follicular reaction in Multiple Sclerosis at clinical onset

2017 ◽  
Author(s):  
Francesca Grassivaro
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
B Cell ◽  
Cell Phenotype ◽  
Clinical Onset ◽  
Igg Synthesis ◽  
Intrathecal Igg Synthesis

Detection of oligoclonal bands as a part of the diagnosis of multiple sclerosis – case studies

2021 ◽  
Vol 57 (2) ◽  
pp. 1-8
Author(s):  
Jolanta Stacherzak-Pawlik ◽  
Paulina Boćko ◽  
Ewa Zagocka
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Autoimmune Diseases ◽  
Oligoclonal Bands ◽  
Multiple Sclerosis Case ◽  
Limit Values ◽  
Igg Synthesis ◽  
Intrathecal Igg Synthesis ◽  
Specific Antigens

Introduction: Oligoclonal bands are the result of the synthesis of antibodies of limited heterogeneity, that is, directed against one or more specific antigens. Their detection is an important element in the diagnosis of autoimmune diseases. In multiple sclerosis, the diagnostic sensitivity of the determination of oligoclonal bands is high. Aim: The aim of this study is to answer the question whether the detection of oligoclonal bands a more valuable study is than the Tibbling-Link index and reibergram analysis in the context of the diagnosis of multiple sclerosis. Material and methods: Oligoclonal bands were tested in the cerebrospinal fluid and serum from 9 patients suspected of multiple sclerosis using the Sebia HYDRAGEL 3 CSF ISOFOCUSING kit. Results: In 7 out of 9 patients the Tibbling-Link index, reibergram analysis and oligoclonal bands detection clearly indicated intrathecal IgG synthesis. In 2 of 9 patients, detection of oligoclonal bands indicated intrathecal IgG synthesis and the value of Tibbling-Link index and reibergram analysis did not indicated intrathecal IgG production or these tests indicated limit values. Conclusions: The detection of oligoclonal bands in many cases allows for faster diagnosis and introduction of therapy. This test should be an integral part of SM diagnostics.

scholarly journals Cerebrospinal Fluid Biomarkers in Relation to MRZ Reaction Status in Primary Progressive Multiple Sclerosis

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2543
Author(s):  
Tilman Robinson ◽  
Ahmed Abdelhak ◽  
Tanima Bose ◽  
Edgar Meinl ◽  
Markus Otto ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
B Cell ◽  
Clinical Features ◽  
Cell Activity ◽  
Csf Biomarkers ◽  
Primary Progressive Multiple Sclerosis ◽  
Primary Progressive ◽  
Mrz Reaction ◽  
Igg Synthesis

The MRZ reaction (MRZR) comprises the three antibody indices (AIs) against measles, rubella, and varicella zoster virus, reflecting an intrathecal polyspecific B cell response highly specific for multiple sclerosis (MS). Thus, MRZR can be used to confirm a diagnosis of primary progressive MS (PPMS) but its pathophysiological and wider clinical relevance is unclear. This study aimed to investigate whether PPMS patients with a positive MRZR (MRZR+) differ from those with a negative MRZR (MRZR-) according to cerebrospinal fluid (CSF) biomarkers of B cell activity, neuroaxonal damage or glial activity, and clinical features. (1) Methods: In a multicenter PPMS cohort (n = 81) with known MRZR status, we measured B cell-activating factor (BAFF), chemokine CXC ligand 13 (CXCL-13), soluble B cell maturation antigen (sBCMA), soluble transmembrane activator and CAML interactor (sTACI), and chitinase-3-like protein 1 (CHI3L1) in the CSF with enzyme-linked immunosorbent assays (ELISAs). Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) were detected in serum and CSF using single molecule array (SIMOA) technology. (2) Results: MRZR+ patients (45.7% of all PPMS patients) revealed higher levels of NfL in CSF compared to MRZR- patients (54.3%). There were positive correlations between each of sBCMA, sTACI, and intrathecal immunoglobin G (IgG) synthesis. Additionally, NfL concentrations in serum positively correlated with those in CSF and those of GFAP in serum. However, MRZR+ and MRZR- patients did not differ concerning clinical features (e.g., age, disease duration, Expanded Disability Status Scale (EDSS) at diagnosis and follow-up); CSF routine parameters; CSF concentrations of BAFF, CXCL-13, sBCMA, sTACI, CHI3L1, and GFAP; or serum concentrations of GFAP and NfL. (3) Conclusions: In PPMS patients, MRZR positivity might indicate a more pronounced axonal damage. Higher levels of the soluble B cell receptors BCMA and transmembrane activator and CAML interactor (TACI) in CSF are associated with a stronger intrathecal IgG synthesis in PPMS.

scholarly journals Comparative characteristic of laboratory indicators for encephalitis, disseminated encephalomyelitis and multiple sclerosis in children

2018 ◽  
Vol 13 (3) ◽  
pp. 25-35
Author(s):  
E. Y. Skripchenko ◽  
L. A. Alekseeva ◽  
N. V. Skripchenko ◽  
T. V. Bessonova
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Immunoglobulin G ◽  
Clinical Manifestations ◽  
Comparative Characteristic ◽  
Control Group ◽  
Humoral Immune ◽  
Igg Synthesis ◽  
Intrathecal Igg Synthesis ◽  
Subsequent Calculation

Background. The similarity of the clinical manifestations of encephalitis (E), disseminated encephalomyelitis (DEM) and multiple sclerosis (MS) in children, the complexity of predicting the nature of the course and outcome of diseases determines the search for additional diagnostic and prognosis criteria.Objective: a comparative characteristic of laboratory indicators for E, DEM and RS in children to assess their diagnostic and prognostic value.Materials and methods. Fifty six children (14 children with E, 14 – with DEM, 28 – with MS) and 16 children of the control group (with acute respiratory virus infection) at the age from 10 to 17 years were examined. Laboratory methods included standard studies of cerebrospinal fluid (protein, cytosis), determination of concentrations of albumin and immunoglobulin G (IgG) in cerebrospinal fluid and serum with subsequent calculation of protein indices (albumin, immunoglobulin, intrathecal immunoglobulin G indexes).Results. With all nosological forms in the serum there were no significant differences between albumin and IgG from the control group, whereas in the cerebrospinal fluid an excess of the concentration of IgG was detected at a normal level of albumin. An increase in the albumin index was found only in E, whereas the immunoglobulin index was significantly higher than the norm in all groups of patients. A significant spread of the intrathecal IgG index (from 0.1 to 11.9) was found, which determined the analysis of clinical and laboratory parameters by subgroups, depending on its magnitude. The maximum incidence of increased intrathecal IgG synthesis was detected in children with MS (with exacerbation of MS – 74 %, in remission – 67 %), whereas in E and DEM, an increase was observed in about half of the patients surveyed and associated with a more favorable course of the disease.Conclusion. The data obtained make it possible to assert that, despite the commonness of some pathogenetic mechanisms, there are differences in the degree of impaired permeability of the blood brain barrier, the intensity of the systemic and intrathecal humoral immune response in E, DEM and RS, which may determine the features of their course and the outcome of the disease, including the transformation of the DEM in the RS.

scholarly journals Cytokines and intrathecal IgG synthesis in multiple sclerosis patients during clinical remission

2005 ◽  
Vol 63 (4) ◽  
pp. 914-919 ◽  
Author(s):  
Carlos Otávio Brandão ◽  
Heloísa Helena Ruocco ◽  
Alessandro dos Santos Farias ◽  
Celina Oliveira ◽  
Dannie Eiko Maeda Hallal-Longo ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Proinflammatory Cytokines ◽  
Clinical Remission ◽  
Cytokine Production ◽  
Inflammatory Activity ◽  
Oligoclonal Bands ◽  
Igg Synthesis ◽  
Intrathecal Igg Synthesis ◽  
Multiple Sclerosis Patients

Cytokines and intrathecal IgG synthesis were determined in the cerebrospinal fluid (CSF) and sera to evaluate inflammatory activity in multiple sclerosis (MS) patients during clinical remission. Although the disease was stable, there had been a significant increase of proinflammatory cytokines such as TNFalpha and IFNgamma in the CSF and serum, with no significant changes of IL12 and IL10 production. The changes in the cytokine production patterns were associated with an increase of leukocytes in the CSF, as well as the presence of oligoclonal bands suggesting intrathecal IgG synthesis. These results suggest that even when the disease is clinically silent, one can observe inflammatory activity in these MS patients.

Cerebrospinal fluid measures of disease activity in patients with multiple sclerosis

1998 ◽  
Vol 4 (6) ◽  
pp. 475-479 ◽  
Author(s):  
Finn Sellebjerg ◽  
Michael Christiansen ◽  
Peter Michael Nielsen ◽  
Jette L Frederiksen
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Disease Activity ◽  
Surrogate Marker ◽  
Albumin Concentration ◽  
Fluid Analysis ◽  
Acute Optic Neuritis ◽  
Igg Synthesis ◽  
Acute Exacerbations ◽  
Intrathecal Igg Synthesis

The potential of magnetic resonance imaging to serve as a surrogate marker of disease activity in patients with multiple sclerosis (MS) is increasingly recognised. In contrast, the use of cerebrospinal fluid analysis has received less attention. We analysed the correlation between clinical data and cerebrospinal fluid parameters in 75 patients with acute optic neuritis (ON) as a possible first symptom of MS, as a symptom of clinically definite MS, and in patients with an attack of MS other than ON. The samples were obtained within 30 days from the onset of an exacerbation. The concentration of myelin basic protein (MBP) in cerebrospinal fluid was significantly correlated with the visual acuity in patients with ON and the Kurtzke EDSS score in patients with MS. The concentration of MBP in CSF also correlated positively with the CSF leukocyte count, intrathecal IgG synthesis, and the CSF-serum albumin concentration quotient. The concentration of MBP in CSF correlated negatively with intrathecal IgA synthesis. The results support the use of the concentration of MBP in CSF as a surrogate marker of disease activity during acute exacerbations of MS; the data also link the presence of MBP in CSF to neuroimmunological parameters.

Tau protein level in cerebrospinal fluid is increased in patients with early multiple sclerosis

2005 ◽  
Vol 11 (3) ◽  
pp. 261-265 ◽  
Author(s):  
J Brettschneider ◽  
M Maier ◽  
S Arda ◽  
A Claus ◽  
S D Süssmuth ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Tau Protein ◽  
Protein A ◽  
Surrogate Marker ◽  
Axonal Damage ◽  
Igg Synthesis ◽  
Significant Difference ◽  
Intrathecal Igg Synthesis ◽  
Normal Controls

Axonal damage has been proposed as the major substrate of permanent clinical disability in multiple sclerosis. Tau protein, a microtubule-associated protein localised in neuronal axons, may serve as a biochemical surrogate marker to evaluate axonal damage in vivo.We intended to determine the extent of axonal damage in different stages and clinical subtypes of MS by investigating cerebrospinal fluid tau concentrations. Tau was measured using an immunoassay in 35 patients with relapsing—remitting MS, eight patients with secondary progressive MS, nine patients with primary progressive MS, 50 patients with clinically isolated syndrome suggestive of early MS and 46 normal controls. Cerebrospinal fluid tau was significantly elevated in MS compared with normal controls (median 206.0 pg/mL versus152.0 pg/mL;P=0.002). No significant difference among different subtypes of MS could be detected, although highest levels were found in very early disease stages. There was a significant elevation of CSF tau among patients with gadolinium-enhancing brain lesions in magnetic resonance imaging (P=0.02) and a tendency towards higher CSF tau levels in patients with pronounced intrathecal IgG synthesis, supporting the notion that axonal damage is influenced by inflammatory activity.

Peripheral imbalanced TFH/TFR ratio correlates with intrathecal IgG synthesis in multiple sclerosis at clinical onset

2018 ◽  
Vol 25 (7) ◽  
pp. 918-926 ◽  
Author(s):  
Marco Puthenparampil ◽  
Antonio Zito ◽  
Giorgia Pantano ◽  
Lisa Federle ◽  
Erica Stropparo ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Oligoclonal Bands ◽  
T Helper ◽  
Germinal Center Reaction ◽  
Clinical Onset ◽  
Follicular Helper ◽  
Igg Synthesis ◽  
Relapsing Remitting ◽  
Intrathecal Igg Synthesis ◽  
Relapsing Remitting Multiple Sclerosis

Background: Alteration of T-follicular helper (TFH) and regulatory (TFR) subpopulations may contribute to the development of auto-reactive B-cell. Objective: To investigate whether changes in TFH and TFR subsets are associated with abnormal IgG synthesis in blood and cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. Methods: Paired blood and CSF samples were obtained from 31 untreated relapsing-remitting multiple sclerosis (RRMS) patients at diagnosis. Peripheral blood TFH (CD3+CD4+CXCR5+CD25–CD127+), TFR (CD3+CD4+CXCR5+CD25+CD127dim), conventional T-Helper (TH, CD3+CD4+CXCR5–CD25–CD127+), and regulatory T-cells (T-Reg, CD3+CD4+CXCR5–CD25+CD127dim) were analyzed in all RRMS patients and in 13 healthy controls (HCs). Qualitative and quantitative intrathecal IgG synthesis was evaluated in RRMS patients, who were then further subclassified according to the presence of IgG oligoclonal bands in blood and/or CSF. Results: Compared to HC, RRMS had lower TFR percentage ( p < 0.01) and higher TFH/TFR ratio ( p < 0.001). In RRMS, TFH/TFR ratio correlated with both qualitative ( r = 0.56, p < 0.005) and quantitative intrathecal IgG synthesis (IgG Index: r = 0.78; IgGLoc: r = 0.79; IgGIF: r = 0.76, all p < 0.001). Patients with the highest TFH/TFR ratios had higher percentages of circulating B-cells (36.1 ± 35.2%, p < 0.05). Conclusion: In RRMS, increased TFH/TFR ratio associates with abnormal IgG production in blood and CSF, suggesting that antibody-producing cells, derived from deregulated peripheral germinal center reaction, colonize the CNS.

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