PLATEFORME BIOMARQUEURS DIAGNOSTIC
| GROUP LEADERS | MICHAEL SEAGAR
GROUP LEADER : EL FAR Oussama
RESEARCH TOPIC :
We have two principal objectives:
• to carry out serological assays for the diagnosis of autoimmune neurological disease
• to carry out the detection of the enzymatic activity of botulinum neurotoxins A, B and E in contaminated samples.
Anti-Cav2 calcium channel antibodies.
In Lambert-Eaton myasthenic syndrome (LEMS), patients produce antibodies against Cav2-type voltage-dependent calcium channels (VGCC). These antibodies reduce calcium-influx into nerve terminals in the peripheral nervous system and thus perturb neurotransmitter release, which leads to muscular weakness and dysfunction of the autonomic nervous system.
In 60 – 70% of cases LEMS is paraneoplastic and the immune response is initiated by a lung tumor. Thus diagnosis of LEMS can lead to early detection of cancer. We routinely perform two serological assays to titer anti-Cav2.1 (P/Q-type) and anti-Cav2.2 (N-type) antibodies.
For further information contact:
Nicole Moutot / EL FAR Oussama
Anti-Kv1 potassium channel antibodies (This activity is curently disrupted).
Circulating antibodies against voltage-dependent Kv1-type potassium channels (VGKC) were initially described in acquired neuromyotonia (Isaac’s syndrome). In this disease of the peripheral nervous system, spontaneous motoneurone discharge leads to myokimia. Anti-Kv1 potassium channel antibodies have also been identified in limbic encephalitis, an autoimmune disease affecting the central nervous system with symptoms such as amnesia, insomnia, hallucinations, seizures and psychosis.
Limbic encephalitis was initially considered to be principally paraneoplastic in origin. However the presence of anti- Kv1 antibodies is now thought to point to a form of limbic encephalitis without associated cancer. In this case immunosuppressive therapy often reduces central symptoms including amnesia. Some patients display both peripheral and central symptoms, a condition known as Morvan syndrome. We routinely perform a serological assay to titer antibodies against Kv1.1, 1.2 and 1.6 channels and the associated protein LGI1.
For further information contact: Nicole Moutot / EL FAR Oussama
The clostridial neurotoxins include tetanus toxin (TeNT) and seven botulinum neurotoxin serotypes (BoNT/ A to G). They induce two severe diseases: tetanus and botulism. BoNT/A and B are also used as therapeutic and cosmetic agents. Using Surface Plasmon Resonance (SPR) technology, we have developed biosensors to assay botulinum and tetanus toxins in complex mixtures (serum and food samples…..) with high sensitivity (Ferracci et al 2011). The biosensors use substrates and monoclonal antibodies that we have generated, which recognize the specific proteolytic signature of each neurotoxin. We are seeking partners to further develop these approaches.
For further information contact:
- 2012 - Formisano-Treziny C, De San Feliciano M, Gabert J.
Development of plasmid calibrators for absolute quantification of miRNAs by using real-time qPCR
J Mol Diagn, 14 : 314-321
- 2012 - Belzeaux R, Bergon A, Jeanjean V, Loriod B, , Formisano-Treziny C, Verrier L, Loundou A, Baumstarck-Barrau K, Boyer L, Gall V, , Gabert J, Nguyen C, Azorin JM, Naudin J, Ibrahim EC.
Responder and nonresponder patients exhibit different peripheral transcriptional signatures during major depressive episodes
Translational Psychiatry, 2 : e185
- 2011 - Ferracci G, Marconi S, Mazuet C, Jover E, Blanchard MP, Seagar M, Popoff M, Lévêque C.
A label-free biosensor assay for botulinum neurotoxin B in food and human serum.
Anal Biochem, 410 : 281-288
- 2008 - Marconi S, Ferracci G, Berthomieu M, Kozaki S, Miquelis R, Boucraut J, Seagar M, Lévêque C.
A protein chip membrane-capture assay for botulinum neurotoxin activity.
Toxicol Appl Pharmacol, 233 : 439-446
- 2008 - Moutot N, De Haro L, Seagar M.
Distinct evolution of calcium channel antibody types in Lambert-Eaton myasthenic syndrome.
J Neuroimmunol, 197 : 47-53
- 2006 - Moutot N, De Haro L, Santos RG, Mori Y, Seagar M.
Phoneutria nigriventer omega-Phonetoxin IIA: a new tool for anti-calcium channel autoantibody assays in Lambert-Eaton myasthenic syndrome.
Neurobiol Dis, 22 : 57-63
- 2005 - Ferracci G, Miquelis R, Kozaki S, Seagar M, Lévêque C.
Synaptic vesicle chips to assay botulinum neurotoxins.
Biochem J, 391 : 659-66
- 2004 - Ferracci G, Seagar M, Joël C, Miquelis R, Lévêque C.
Real time analysis of intact organelles using surface plasmon resonance.
Anal Biochem, 334 : 367-375
- 2004 - Moutot N, De Haro L, Seagar M.
[Dosage and specificity of anti-calcium channel antibodies in Lambert-Eaton myasthenic syndrome].
Rev Neurol (Paris), 165 : S28-S34
- 1999 - Raymond C, Walker D, Bichet D, Iborra C, Moutot N, Seagar M, De Waard M.
Antibodies against the beta subunit of voltage-dependent calcium channels in Lambert-Eaton myasthenic syndrome.
Neuroscience, 90 : 269-277
- 1998 - Seagar M, Moutot N, Raymond C, Charvin N, Lévêque C, Walker D, De Waard M.
Omega-conotoxins : diagnostic tools for an autoimmune disease of the neuromuscular juction
Toxicon, 36 : 1730-1731
- 1996 - Arsac C, Raymond C, Moutot N, Dargent B, Couraud F, Poget J, Seagar M.
Immunoassays fail to detect antibodies against neuronal calcium channels in amyotrophic lateral sclerosis serum.
Ann Neurol, 40 : 695-700
- 1995 - Seagar M, Moutot N, Lévêque C, Marqueze B, Pouget J.
Anti-calcium channel autoantibodies in amyotrophic lateral sclerosis. A review of the evidence.
Adv Neurol, 68 : 67-72
- 1993 - David P, Moutot N, Lévêque C, El Far O, Takahashi M, Seagar M.
Interaction of synaptotagmin with voltage gated calcium channels: a role in Lambert-Eaton myasthenic syndrome?
Neuromuscul Disord, 3 : 451-454
- 1993 - David P, El Far O, Moutot N, Poupon MF, Takahashi M, Seagar M.
Expression of synaptotagmin and syntaxin associated with N-type calcium channels in small cell lung cancer.
FEBS Lett, 326 : 135-139
- 1993 - Seagar M, Moutot N, Lévêque C, El Far O, David P, Marqueze B, Lang B, Newsom-Davis J, Hoshino T, Takahashi M.
A Lambert-Eaton myasthenic syndrome antigen associated with presynaptic calcium channels.
Biochem Soc Trans, 21 : 423-428
- 1993 - Moutot N, El Far O, Lévêque C, David P, Marqueze B, Lang B, Newsom-Davis J, Hoshino T, Takahashi M, Seagar M.
Synaptotagmin: a Lambert-Eaton myasthenic syndrome antigen that associates with presynaptic calcium channels.
J Physiol Paris, 87 : 37-41
- 1992 - Lévêque C, Hoshino T, David P, Shoji-Kasai Y, Leys K, Omori A, Lang B , El Far O, Sato K, Newsom-Davis J, Takahashi M, Moutot N, Seagar M.
The synaptic vesicle protein synaptotagmin associates with calcium channels and is a putative Lambert-Eaton myasthenic syndrome antigen.
Proc Natl Acad Sci U S A, 89 : 3625-3629