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9. Serum neurofilament light chain levels are increased in patients with a clinically isolated syndrome

Author

Disanto, G1, Adiutori, R2, Dobson, R2, Martinelli, V3, Dalla Costa G3, Runia, T4, Evdoshenko, E5, Thouvenot, E6, Trojano, M7, Norgren, N8, Teunissen, C9, Kappos, L10, Giovannoni, G2, Kuhle, J, Bianchi, L, Topping, J, Bestwick, Jp, Meier, Uc, Lazareva, N, Iaffaldano, P, Direnzo, V, Khademi, M, Piehl, F, Comabella, M, Sombekke, M, Killestein, J, Hegen, H, Rauch, S, D'Alfonso, S, Alvarez-Cermeño, Jc, Kleinová, P, Horáková, D, Roesler, R, Lauda, F, Llufriu, S, Avsar, T, Uygunoglu, U, Altintas, A, Saip, S, Menge, T, Rajda, C, Bergamaschi, R, Moll, N, Khalil, M, Marignier, R, Dujmovic, I, Larsson, H, Malmestrom, C, Scarpini, E, Fenoglio, C, Wergeland, S, Laroni, A, Annibali, V, Romano, S, Martínez, Ad, Carra, A, Salvetti, M, Uccelli, A, Torkildsen, Ø, Myhr, Km, Galimberti, D, Rejdak, K, Lycke, J, Frederiksen, Jl, Drulovic, J, Confavreux, C, Brassat, D, Enzinger, C, Fuchs, S, Bosca, I, Pelletier, J, Picard, C, Colombo, E, Franciotta, D, Derfuss, T, Lindberg, Rl, Yaldizli, Ö, Vécsei, L, Kieseier, Bc, Hartung, Hp, Villoslada, P, Siva, A, Saiz, A, Tumani, H, Havrdová, E, Villar, Lm, Leone, M, Barizzone, N, Deisenhammer, F, Montalban, X, Tintoré, M, Olsson, T, Lehmann, S, Castelnovo, G, Lapin, S, Hintzen, R, Furlan, R, Comi, G, Ramagopalan, Sv., Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Laboratory Medicine, Amsterdam Neuroscience - Neuroinfection & -inflammation, Disanto, G., Adiutori, R., Dobson, R., Martinelli, V., Dalla Costa, G., Runia, T., Evdoshenko, E., Thouvenot, E., Trojano, M., Norgren, N., Teunissen, C., Kappos, L., Giovannoni, G., Kuhle, J., on behalf of the International ClinicallyIsolated Syndrome Study, Group, and Neurology

Subjects
Male, Pathology, Future studies, Gastroenterology, 0302 clinical medicine, Neurofilament Proteins, Multiple Sclerosi, 0303 health sciences, Clinically isolated syndrome, medicine.diagnostic_test, Medicine (all), Neurofilament Protein, Demyelinating Disease, Magnetic Resonance Imaging, Psychiatry and Mental Health, Predictive value of tests, Disease Progression, Biomarker (medicine), [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Human, Adult, medicine.medical_specialty, Multiple Sclerosis, Neurofilament light, multiple sclerosis, adult, axons, biomarkers, demyelinating diseases, disease progression, female, follow-up studies, humans, magnetic resonance imaging, male, neurofilament proteins, predictive value of tests, neurology (clinical), psychiatry and mental health, surgery, arts and humanities (miscellaneous), medicine (all), [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Axon, Follow-Up Studie, 03 medical and health sciences, Arts and Humanities (miscellaneous), Predictive Value of Tests, Internal medicine, medicine, Humans, In patient, MULTIPLE SCLEROSIS, 030304 developmental biology, business.industry, Multiple sclerosis, Magnetic resonance imaging, Biomarker, medicine.disease, Axons, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Surgery, Neurology (clinical), business, 030217 neurology & neurosurgery, Biomarkers, Demyelinating Diseases, Follow-Up Studies
Abstract

International audience; BACKGROUND:Neurofilament light chain (NfL) represents a promising biomarker for axonal injury. We present the first exploratory study on serum NfL in patients with a clinically isolated syndrome (CIS) and healthy controls.METHODS:We investigated serum NfL levels in 100 patients with CIS with a short conversion interval to clinically definite multiple sclerosis (MS) (fast converters (FC), median (IQR) conversion time: 110 days (79-139)); 98 patients with non-converting CIS (non-converters (NC), follow-up: 6.5 years (5.3-7.9)); and 92 healthy controls.RESULTS:NfL levels were higher in FC (24.1 pg/mL (13.5-51.8)) and NC (19.3 pg/mL (13.6-35.2)) than in healthy controls (7.9 pg/mL (5.6-17.2)) (OR=5.85; 95% CI 2.63 to 13.02; p = 1.5 × 10(-5) and OR = 7.03; 95% CI 2.85 to 17.34; p = 2.3 × 10(-5), respectively). When grouping FC and NC, increased serum NfL concentration was also associated with increasing numbers of T2 hyperintense MRI lesions (OR = 2.36; 95% CI 1.21 to 4.59; p = 0.011), gadolinium-enhancing lesions (OR = 2.69; 95% CI 1.13 to 6.41; p=0.026) and higher disability scores (OR = 2.54; 95% CI 1.21 to 5.31; p = 0.013) at CIS diagnosis.CONCLUSIONS:If replicated in future studies, serum NfL may represent a reliable and easily accessible biomarker of early axonal damage in CIS and MS.

Published
2016

11. Patient Associated Factors that Affect Adherence to Warfarin Therapy in a Tertiary Referral Hospital in Kenya

Author

Mariita, K., Nyamu, D. G., Maina, C. K., Karimi, P. N., Mugendi, G. A., and Menge, T. B.

Subjects
Warfarin, adherence, patient factors, Kenya
Abstract

Warfarin is the most widely used oral anticoagulant but non-adherence to its therapy contributes significantly to sub-optimal anticoagulation control. A crosssectional study was carried out among 147 adult outpatients at Kenyatta National Hospital to determine the level of adherence and explore the associated factors. Adherence was associated with age, gender heart valve surgery, alcohol consumption, and cost of treatment. On multivariate analysis, the independent variables associated with adequate adherence were age (OR = 0.429, 95% CI = 0.228-0.808; p = 0.009), gender (OR = 0.299, 95% CI = 0.123-0.728; p = 0.008) and the type of thromboembolic disease (OR = 0.385, 95% CI = 0.214-0.690; p = 0.001). Adherence was better among females, older age groups and patients who had undergone heart valve surgery. Adherence was poorer among males, younger participants and patients with venous thromboembolism. We suggest that medication adherence counseling to warfarin therapy should be emphasized in poor-adherent patient populations.Key words: Warfarin, adherence, patient factors, Kenya

Published
2018

14. Epstein-Barr-negative MS: a true phenomenon?

Author

Dobson, Ruth, Kuhle, Jens, Middeldorp, Jaap, Giovannoni, Gavin, on behalf of the international CIS study investigators including Dalla Costa, G, Furlan, R, Martinelli, V, Comi, G, Runia, T, Hintzen, R, Evdoshenko, E, Lazareva, N, Lapin, S, Thouvenot, E, Lehmann, S, Castelnovo, G, Iaffaldano, P, Direnzo, V, Trojano, M, Khademi, . M, Piehl, F, Olsson, T, Comabella, M, Montalban, X, Tintoré, M, Sombekke, M, Killestein, J, Teunissen, C, Hegen, H, Deisenhammer, F, Rauch, S, D'Alfonso, S, Barizzone, N, Alvarez Cermeño, Jc, Villar, Lm, Kleinová, P, Horáková, D, Havrdová, E, Roesler, R, Lauda, F, Tumani, H, Llufriu, S, Villoslada, P, Saiz, A, Avsar, T, Uygunoglu, U, Altintas, A, Saip, S, Siva, A, Menge, T, Kieseier, Bc, Hartung, Hp, Rajda, C, Vécsei, L, Bergamaschi, R, Colombo, E, Franciotta, D, Moll, N, Pelletier, J, Picard, C, Khalil, M, Enzinger, C, Fuchs, S, Marignier, R, Confavreux, C, Dujmovic, I, Drulovic, J, Larsson, H, Malmestrom, C, Lycke, J, Scarpini, E, C. Fenoglio, C, Galimberti, D, Wergeland, S, Torkildsen, Ø, Myhr, Km, Laroni, Alice, Uccelli, Antonio, Annibali, V, Romano, S, Salvetti, M, Martínez, Ad, Carra, A, Rejdak, K, Frederiksen, Jl, Brassat, D, Bosca, I, Casanova, B, Derfuss, T, Lindberg, R, Yaldizli, Ö, Kappos, L, Leone, M., and Pathology

Subjects
0301 basic medicine, business.industry, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Neurology, Epstein barr, Phenomenon, Medicine, Neurology (clinical), business, Competence (human resources), Social psychology, Clinical/Scientific Notes, 030217 neurology & neurosurgery
Abstract

This work was supported by institutional funding and in part by the BMBF grant KKNMS (Competence Net Multiple Sclerosis) to H Tumani.

Published
2017

16. Drivers of airborne human-to-human pathogen transmission

Author

Herfst, S. (Sander), Böhringer, M. (Michael), Karo, B. (Basel), Lawrence, P. (Philip), Lewis, N.S. (Nicola), Mina, M.J. (Michael J.), Russell, C.J. (Charles J), Steel, J. (John), Swart, R.L. (Rik) de, Menge, T. (Til), Herfst, S. (Sander), Böhringer, M. (Michael), Karo, B. (Basel), Lawrence, P. (Philip), Lewis, N.S. (Nicola), Mina, M.J. (Michael J.), Russell, C.J. (Charles J), Steel, J. (John), Swart, R.L. (Rik) de, and Menge, T. (Til)

Abstract

Airborne pathogens — either transmitted via aerosol or droplets — include a wide variety of highly infectious and dangerous microbes such as variola virus, measles virus, influenza A viruses, Mycobacterium tuberculosis, Streptococcus pneumoniae, and Bordetella pertussis. Emerging zoonotic pathogens, for example, MERS coronavirus, avian influenza viruses, Coxiella, and Francisella, would have pandemic potential were they to acquire efficient human-to-human transmissibility. Here, we synthesize insights from microbiological, medical, social, and economic sciences to provide known mechanisms of aerosolized transmissibility and identify knowledge gaps that limit emergenc

Published
2017
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23. Conversion from clinically isolated syndrome to multiple sclerosis:A large multicentre study

Author

Kuhle, J, Disanto, G, Dobson, R, Adiutori, R, Bianchi, L, Topping, J, Bestwick, J P, Meier, U-C, Marta, M, Dalla Costa, G, Runia, T, Evdoshenko, E, Lazareva, N, Thouvenot, E, Iaffaldano, P, Direnzo, V, Khademi, M, Piehl, F, Comabella, M, Sombekke, M, Killestein, J, Hegen, H, Rauch, S, D'Alfonso, S, Alvarez-Cermeño, J C, Kleinová, P, Horáková, D, Roesler, R, Lauda, F, Llufriu, S, Avsar, T, Uygunoglu, U, Altintas, A, Saip, S, Menge, T, Rajda, C, Bergamaschi, R, Moll, N, Khalil, M, Marignier, R, Dujmovic, I, Larsson, H, Malmestrom, C, Scarpini, E, Fenoglio, C, Wergeland, S, Laroni, A, Annibali, V, Romano, S, Martínez, A D, Carra, A, Salvetti, M, Uccelli, A, Torkildsen, Ø, Myhr, K M, Galimberti, D, Rejdak, K, Lycke, J, Fredriksen, Jette Lautrup, Drulovic, J, Confavreux, C, Brassat, D, Enzinger, C, Fuchs, S, Bosca, I, Pelletier, J, Picard, C, Colombo, E, Franciotta, D, Derfuss, T, Lindberg, Rlp, Yaldizli, Ö, Vécsei, L, Kieseier, B C, Hartung, H P, Villoslada, P, Siva, A, Saiz, A, Tumani, H, Havrdová, E, Villar, L M, Leone, M, Barizzone, N, Deisenhammer, F, Teunissen, C, Montalban, X, Tintoré, M, Olsson, T, Trojano, M, Lehmann, S, Castelnovo, G, Lapin, S, Hintzen, R, Kappos, L, Furlan, R, Martinelli, V, Comi, G, Ramagopalan, S V, Giovannoni, G, Kuhle, J, Disanto, G, Dobson, R, Adiutori, R, Bianchi, L, Topping, J, Bestwick, J P, Meier, U-C, Marta, M, Dalla Costa, G, Runia, T, Evdoshenko, E, Lazareva, N, Thouvenot, E, Iaffaldano, P, Direnzo, V, Khademi, M, Piehl, F, Comabella, M, Sombekke, M, Killestein, J, Hegen, H, Rauch, S, D'Alfonso, S, Alvarez-Cermeño, J C, Kleinová, P, Horáková, D, Roesler, R, Lauda, F, Llufriu, S, Avsar, T, Uygunoglu, U, Altintas, A, Saip, S, Menge, T, Rajda, C, Bergamaschi, R, Moll, N, Khalil, M, Marignier, R, Dujmovic, I, Larsson, H, Malmestrom, C, Scarpini, E, Fenoglio, C, Wergeland, S, Laroni, A, Annibali, V, Romano, S, Martínez, A D, Carra, A, Salvetti, M, Uccelli, A, Torkildsen, Ø, Myhr, K M, Galimberti, D, Rejdak, K, Lycke, J, Fredriksen, Jette Lautrup, Drulovic, J, Confavreux, C, Brassat, D, Enzinger, C, Fuchs, S, Bosca, I, Pelletier, J, Picard, C, Colombo, E, Franciotta, D, Derfuss, T, Lindberg, Rlp, Yaldizli, Ö, Vécsei, L, Kieseier, B C, Hartung, H P, Villoslada, P, Siva, A, Saiz, A, Tumani, H, Havrdová, E, Villar, L M, Leone, M, Barizzone, N, Deisenhammer, F, Teunissen, C, Montalban, X, Tintoré, M, Olsson, T, Trojano, M, Lehmann, S, Castelnovo, G, Lapin, S, Hintzen, R, Kappos, L, Furlan, R, Martinelli, V, Comi, G, Ramagopalan, S V, and Giovannoni, G

Abstract

BACKGROUND AND OBJECTIVE: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort.METHODS: Thirty-three centres provided serum samples from 1047 CIS cases with at least two years' follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS.RESULTS: At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71-2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52-2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04-3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98-0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres.CONCLUSIONS: We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.

Published
2015

26. Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study

Author

Kuhle, J, primary, Disanto, G, additional, Dobson, R, additional, Adiutori, R, additional, Bianchi, L, additional, Topping, J, additional, Bestwick, JP, additional, Meier, U-C, additional, Marta, M, additional, Costa, G Dalla, additional, Runia, T, additional, Evdoshenko, E, additional, Lazareva, N, additional, Thouvenot, E, additional, Iaffaldano, P, additional, Direnzo, V, additional, Khademi, M, additional, Piehl, F, additional, Comabella, M, additional, Sombekke, M, additional, Killestein, J, additional, Hegen, H, additional, Rauch, S, additional, D’Alfonso, S, additional, Alvarez-Cermeño, JC, additional, Kleinová, P, additional, Horáková, D, additional, Roesler, R, additional, Lauda, F, additional, Llufriu, S, additional, Avsar, T, additional, Uygunoglu, U, additional, Altintas, A, additional, Saip, S, additional, Menge, T, additional, Rajda, C, additional, Bergamaschi, R, additional, Moll, N, additional, Khalil, M, additional, Marignier, R, additional, Dujmovic, I, additional, Larsson, H, additional, Malmestrom, C, additional, Scarpini, E, additional, Fenoglio, C, additional, Wergeland, S, additional, Laroni, A, additional, Annibali, V, additional, Romano, S, additional, Martínez, AD, additional, Carra, A, additional, Salvetti, M, additional, Uccelli, A, additional, Torkildsen, Ø, additional, Myhr, KM, additional, Galimberti, D, additional, Rejdak, K, additional, Lycke, J, additional, Frederiksen, JL, additional, Drulovic, J, additional, Confavreux, C, additional, Brassat, D, additional, Enzinger, C, additional, Fuchs, S, additional, Bosca, I, additional, Pelletier, J, additional, Picard, C, additional, Colombo, E, additional, Franciotta, D, additional, Derfuss, T, additional, Lindberg, RLP, additional, Yaldizli, Ö, additional, Vécsei, L, additional, Kieseier, BC, additional, Hartung, HP, additional, Villoslada, P, additional, Siva, A, additional, Saiz, A, additional, Tumani, H, additional, Havrdová, E, additional, Villar, LM, additional, Leone, M, additional, Barizzone, N, additional, Deisenhammer, F, additional, Teunissen, C, additional, Montalban, X, additional, Tintoré, M, additional, Olsson, T, additional, Trojano, M, additional, Lehmann, S, additional, Castelnovo, G, additional, Lapin, S, additional, Hintzen, R, additional, Kappos, L, additional, Furlan, R, additional, Martinelli, V, additional, Comi, G, additional, Ramagopalan, SV, additional, and Giovannoni, G, additional

Published
2015
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27. Neurofilament ELISA validation

Author

Petzold, A. Altintas, A. Andreoni, L. Bartos, A. Berthele, A. Blankenstein, M.A. Buee, L. Castellazzi, M. Cepok, S. Comabella, M. Constantinescu, C.S. Deisenhammer, F. Deniz, G. Erten, G. Espiño, M. Fainardi, E. Franciotta, D. Freedman, M.S. Giedraitis, V. Gilhus, N.E. Giovannoni, G. Glabinski, A. Grieb, P. Hartung, H.-P. Hemmer, B. Herukka, S.-K. Hintzen, R. Ingelsson, M. Jackson, S. Jacobsen, S. Jafari, N. Jalosinski, M. Jarius, S. Kapaki, E. Kieseier, B.C. Koel-Simmelink, M.J.A. Kornhuber, J. Kuhle, J. Kurzepa, J. Lalive, P.H. Lannfelt, L. Lehmensiek, V. Lewczuk, P. Livrea, P. Marnetto, F. Martino, D. Menge, T. Norgren, N. Papuć, E. Paraskevas, G.P. Pirttilä, T. Rajda, C. Rejdak, K. Ricny, J. Ripova, D. Rosengren, L. Ruggieri, M. Schraen, S. Shaw, G. Sindic, C. Siva, A. Stigbrand, T. Stonebridge, I. Topcular, B. Trojano, M. Tumani, H. Twaalfhoven, H.A.M. Vécsei, L. Van Pesch, V. Vanderstichele, H. Vedeler, C. Verbeek, M.M. Villar, L.M. Weissert, R. Wildemann, B. Yang, C. Yao, K. Teunissen, C.E.

Abstract

Background: Neurofilament proteins (Nf) are highly specific biomarkers for neuronal death and axonal degeneration. As these markers become more widely used, an inter-laboratory validation study is required to identify assay criteria for high quality performance. Methods: The UmanDiagnostics NF-light ®enzyme-linked immunoabsorbent assays (ELISA) for the neurofilament light chain (NfL, 68 kDa) was used to test the intra-assay and inter-laboratory coefficient of variation (CV) between 35 laboratories worldwide on 15 cerebrospinal fluid (CSF) samples. Critical factors, such as sample transport and storage, analytical delays, reaction temperature and time, the laboratories' accuracy and preparation of standards were documented and used for the statistical analyses. Results: The intra-laboratory CV averaged 3.3% and the inter-laboratory CV 59%. The results from the test laboratories correlated with those from the reference laboratory (R = 0.60, p < 0.0001). Correcting for critical factors improved the strength of the correlation. Differences in the accuracy of standard preparation were identified as the most critical factor. Correcting for the error introduced by variation in the protein standards improved the correlation to R = 0.98, p < 0.0001 with an averaged inter-laboratory CV of 14%. The corrected overall inter-rater agreement was subtantial (0.6) according to Fleiss' multi-rater kappa and Gwet's AC1 statistics. Conclusion: This multi-center validation study identified the lack of preparation of accurate and consistent protein standards as the main reason for a poor inter-laboratory CV. This issue is also relevant to other protein biomarkers based on this type of assay and will need to be solved in order to achieve an acceptable level of analytical accuracy. The raw data of this study is available online. © 2009 Elsevier B.V.

Published
2010

28. Crossing the Interspecies Barrier: Opening the Door to Zoonotic Pathogens

Author

Gortazar, C. (Christian), Reperant, L.A. (Leslie), Kuiken, T. (Thijs), de la Fuente, L., Boadella, M. (Mariana), Martínez-Lopez, B. (Beatriz), Ruiz-Fons, F. (Francisco), Estrada-Peña, A. (Agustin), Drosten, C. (Christian), Medley, G. (Graham), Ostfeld, R. (Richard), Peterson, T. (Townsend), VerCauteren, K.C. (Kurt), Menge, T. (Til), Artois, M. (Marc), Schultsz, C. (Constance), Delahay, R. (Richard), Serra-Cobo, J. (Jordi), Poulin, R. (Robert), Keck, F. (Frederic), Aguirre, A.A. (Alonso), Henttonen, H. (Heikki), Dobson, A.P. (Andrew), Kutz, P. (Patrizia), Lubroth, J. (Juan), Mysterud, A. (Atle), Gortazar, C. (Christian), Reperant, L.A. (Leslie), Kuiken, T. (Thijs), de la Fuente, L., Boadella, M. (Mariana), Martínez-Lopez, B. (Beatriz), Ruiz-Fons, F. (Francisco), Estrada-Peña, A. (Agustin), Drosten, C. (Christian), Medley, G. (Graham), Ostfeld, R. (Richard), Peterson, T. (Townsend), VerCauteren, K.C. (Kurt), Menge, T. (Til), Artois, M. (Marc), Schultsz, C. (Constance), Delahay, R. (Richard), Serra-Cobo, J. (Jordi), Poulin, R. (Robert), Keck, F. (Frederic), Aguirre, A.A. (Alonso), Henttonen, H. (Heikki), Dobson, A.P. (Andrew), Kutz, P. (Patrizia), Lubroth, J. (Juan), and Mysterud, A. (Atle)

Published
2014
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29. Antibodies to native myelin oligodendrocyte glycoprotein are serologic markers of early inflammation in multiple sclerosis

Author

Ph, Lalive, Menge, T., Delarasse, C., Gaspera B, Della, Pham-Dinh, D., Villoslada, P., Budingen Hc, Von, Cp, Genain, Neurobiologie des réseaux sensorimoteurs (NRS (U7060)), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Magnani, Christophe, Neurobiologie des réseaux sensorimoteurs ( NRS (U7060) ), and Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
[ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Published
2006

30. Antibodies to native myelin oligodendrocyte glycoprotein are serologic markers of early inflammation in multiple sclerosis

Author

Lalive, P.H. (Patrice H.), Menge, T. (Til), Delarasse, C. (Cecile), Gaspera, B.D. (Bruno Della), Pham-Dinh, D. (Danielle), Villoslada, P. (Pablo), Budingen, H.C. (H.C.) von, and Genain, C.P. (Claude P.)

Subjects
Multiple sclerosis, nervous system, immune system diseases, Oligodendrocyte glycoprotein, Antibodies
Abstract

Myelin oligodendrocyte glycoprotein (MOG) is an integral membrane protein expressed in CNS oligodendrocytes and outermost myelin lamellae. Anti-MOG Abs cause myelin destruction (demyelination) in animal models of multiple sclerosis (MS); however, such pathogenic Abs have not yet been characterized in humans. Here, a method that specifically detects IgG binding to human MOG in its native, membrane-embedded conformation on MOG-transfected mammalian cells was used to evaluate the significance of these auto Abs. Compared with healthy controls, native MOG-specific IgGs were most frequently found in serum of clinically isolated syndromes (P < 0.001) and relapsing-remitting MS (P < 0.01), only marginally in secondary progressive MS (P < 0.05), and not at all in primary progressive MS. We demonstrate that epitopes exposed in this cell-based assay are different from those exposed on the refolded, extracellular domain of human recombinant MOG tested by solid-phase ELISA. In marmoset monkeys induced to develop MS-like CNS inflammatory demyelination, IgG reactivity against the native membrane-bound MOG is always detected before clinical onset of disease (P < 0.0001), unlike that against other myelin constituents. We conclude that (i) epitopes displayed on native, glycosylated MOG expressed in vivo are early targets for pathogenic Abs; (ii) these Abs, which are not detected in solid-phase assays, might be the ones to play a pathogenic role in early MS with predominant inflammatory activity; and (iii) the cell-based assay provides a practical serologic marker for early detection of CNS autoimmune demyelination including its preclinical stage at least in the primate MS model

Published
2006

32. Guidelines for uniform reporting of body fluid biomarker studies in neurologic disorders

Author

Gnanapavan, S., primary, Hegen, H., additional, Khalil, M., additional, Hemmer, B., additional, Franciotta, D., additional, Hughes, S., additional, Hintzen, R., additional, Jeromin, A., additional, Havrdova, E., additional, Tumani, H., additional, Bertolotto, A., additional, Comabella, M., additional, Frederiksen, J., additional, Alvarez-Cermeno, J. C., additional, Villar, L., additional, Galimberti, D., additional, Myhr, K.-M., additional, Dujmovic, I., additional, Fazekas, F., additional, Ionete, C., additional, Menge, T., additional, Kuhle, J., additional, Keir, G., additional, Deisenhammer, F., additional, Teunissen, C., additional, and Giovannoni, G., additional

Published
2014
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34. Neurofilament ELISA validation.

Author

Petzold, A., Altintas, A., Andreoni, L., Bartos, A., Berthele, A., Blankenstein, M.A., Buee, L., Castellazzi, M., Cepok, S., Comabella, M., Constantinescu, C.S., Deisenhammer, F., Deniz, G., Erten, G., Espino, M., Fainardi, E., Franciotta, D., Freedman, M.S., Giedraitis, V., Gilhus, N.E., Giovannoni, G., Glabinski, A., Grieb, P., Hartung, H.P., Hemmer, B., Herukka, S.K., Hintzen, R., Ingelsson, M., Jackson, S., Jacobsen, S., Jafari, N., Jalosinski, M., Jarius, S., Kapaki, E., Kieseier, B.C., Koel-Simmelink, M.J., Kornhuber, J., Kuhle, J., Kurzepa, J., Lalive, P.H., Lannfelt, L., Lehmensiek, V., Lewczuk, P., Livrea, P., Marnetto, F., Martino, D., Menge, T., Norgren, N., Papuc, E., Paraskevas, G.P., Pirttilä, T., Rajda, C., Rejdak, K., Ricny, J., Ripova, D., Rosengren, L., Ruggieri, M., Schraen, S., Shaw, G., Sindic, C., Siva, A., Stigbrand, T., Stonebridge, I., Topcular, B., Trojano, M., Tumani, H., Twaalfhoven, H.A., Vecsei, L., Pesch, V. Van, Vanderstichele, H., Vedeler, C., Verbeek, M.M., Villar, L.M., Weissert, R., Wildemann, B., Yang, C., Yao, K., Teunissen, C.E., Petzold, A., Altintas, A., Andreoni, L., Bartos, A., Berthele, A., Blankenstein, M.A., Buee, L., Castellazzi, M., Cepok, S., Comabella, M., Constantinescu, C.S., Deisenhammer, F., Deniz, G., Erten, G., Espino, M., Fainardi, E., Franciotta, D., Freedman, M.S., Giedraitis, V., Gilhus, N.E., Giovannoni, G., Glabinski, A., Grieb, P., Hartung, H.P., Hemmer, B., Herukka, S.K., Hintzen, R., Ingelsson, M., Jackson, S., Jacobsen, S., Jafari, N., Jalosinski, M., Jarius, S., Kapaki, E., Kieseier, B.C., Koel-Simmelink, M.J., Kornhuber, J., Kuhle, J., Kurzepa, J., Lalive, P.H., Lannfelt, L., Lehmensiek, V., Lewczuk, P., Livrea, P., Marnetto, F., Martino, D., Menge, T., Norgren, N., Papuc, E., Paraskevas, G.P., Pirttilä, T., Rajda, C., Rejdak, K., Ricny, J., Ripova, D., Rosengren, L., Ruggieri, M., Schraen, S., Shaw, G., Sindic, C., Siva, A., Stigbrand, T., Stonebridge, I., Topcular, B., Trojano, M., Tumani, H., Twaalfhoven, H.A., Vecsei, L., Pesch, V. Van, Vanderstichele, H., Vedeler, C., Verbeek, M.M., Villar, L.M., Weissert, R., Wildemann, B., Yang, C., Yao, K., and Teunissen, C.E.

Abstract

Contains fulltext : 89601.pdf (publisher's version ) (Closed access), BACKGROUND: Neurofilament proteins (Nf) are highly specific biomarkers for neuronal death and axonal degeneration. As these markers become more widely used, an inter-laboratory validation study is required to identify assay criteria for high quality performance. METHODS: The UmanDiagnostics NF-light (R)enzyme-linked immunoabsorbent assays (ELISA) for the neurofilament light chain (NfL, 68kDa) was used to test the intra-assay and inter-laboratory coefficient of variation (CV) between 35 laboratories worldwide on 15 cerebrospinal fluid (CSF) samples. Critical factors, such as sample transport and storage, analytical delays, reaction temperature and time, the laboratories' accuracy and preparation of standards were documented and used for the statistical analyses. RESULTS: The intra-laboratory CV averaged 3.3% and the inter-laboratory CV 59%. The results from the test laboratories correlated with those from the reference laboratory (R=0.60, p<0.0001). Correcting for critical factors improved the strength of the correlation. Differences in the accuracy of standard preparation were identified as the most critical factor. Correcting for the error introduced by variation in the protein standards improved the correlation to R=0.98, p<0.0001 with an averaged inter-laboratory CV of 14%. The corrected overall inter-rater agreement was subtantial (0.6) according to Fleiss' multi-rater kappa and Gwet's AC1 statistics. CONCLUSION: This multi-center validation study identified the lack of preparation of accurate and consistent protein standards as the main reason for a poor inter-laboratory CV. This issue is also relevant to other protein biomarkers based on this type of assay and will need to be solved in order to achieve an acceptable level of analytical accuracy. The raw data of this study is available online.

Published
2010

37. Neuromyelitis optica and pregnancy during therapeutic B cell depletion: infant exposure to anti-AQP4 antibody and prevention of rebound relapses with low-dose rituximab postpartum

Author

Ringelstein, M, primary, Harmel, J, additional, Distelmaier, F, additional, Ingwersen, J, additional, Menge, T, additional, Hellwig, K, additional, Kieseier, B, additional, Mayatepek, E, additional, Hartung, H-P, additional, Kuempfel, T, additional, and Aktas, O, additional

Published
2013
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50. Highly reactive anti-myelin oligodendrocyte glycoprotein antibodies differentiate demyelinating diseases from viral encephalitis in children.

Author

Lalive, P. H., Häusler, M. G., Maurey, H., Mikaeloff, Y., Tardieu, M., Wiendl, H., Schroeter, M., Hartung, H. P., Kieseier, B. C., and Menge, T.

Subjects
POSTVACCINAL encephalitis, AUTOANTIBODIES, EPSTEIN-Barr virus, GLYCOPROTEINS, MULTIPLE sclerosis in children, CYTOMETRY, DEMYELINATION
Abstract

Background: Myelin oligodendrocyte glycoprotein (MOG) may be implicated in the immunopathogenesis of multiple sclerosis (MS) inducing demyelination in the animal model of MS. In adults reported anti-MOG antibody frequencies have been variable across a number of studies and can also be detected in controls.Objective: To measure antibodies against MOG in paediatric patients with demyelinating disorders of the central nervous system and in controls.Methods: Serum antibodies against MOG and myelin basic protein were measured by ELISA, flow cytometry (FACS) and in the liquid phase in 11 children with acute disseminated encephalomyelitis (ADEM), 22 children with MS, seven children with acute viral encephalitis and 13 healthy controls. The serostatus of Epstein—Barr virus (EBV) infections were assessed.Results: Anti-MOG antibodies, measured either by ELISA or FACS were exclusively detected in children with demyelination. In ADEM these antibodies were highly reactive. Anti-MBP reactivity was detectable equally in all groups. The presence of either autoantibodies did not associate with EBV serostatus, age, gender or disease course.Conclusions: This study independently corroborates recently published results of seroprevalence and specificity of the assay. Due to their low sensitivity anti-MOG antibodies will not serve as disease-specific biomarkers, but could help to support the diagnosis of ADEM in difficult cases. [ABSTRACT FROM PUBLISHER]

Published
2011
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