Laboratory Lead: Dr Melanie Hart
Clinical Lead and Consultant Neurologist: Dr Michael Lunn
Honorary Senior Lecturer and Consultant Neurologist: Dr Michael Zandi
The Neuroimmunology and CSF Laboratory Unit at the Institute of Neurology is one of only very few specialist NHS Neuroimmunology Laboratories in the UK and provides a hub for CSF and Neuroimmunology testing for UCLH, the Greater London network and beyond. The lab is situated adjacent to and serves the National Hospital for Neurology and Neurosurgery (NHNN) and both are part of University College Hospitals NHS Trust. The NHS Neuroimmunology service has developed over the last thirty-five years in collaboration with Emeritus Professor Edward Thompson. A strong focus on in-house research has led to the development of many novel diagnostic assays for neurology such as the oligoclonal bands test (OCBS) developed to aid diagnosis of Multiple Sclerosis and still in use today throughout the world. The laboratory now provides a comprehensive neuroimmunology testing service to physicians in the UK and beyond. Staff hold honorary contracts with University College London (UCL) and some are present on external quality assurance steering committees for CSF analysis, providing expert guidance and pursuing research, notably in xanthochromia testing.
The team at NICL is at the forefront of biomarker research into many neurological and neuroinflammatory diseases including Multiple Sclerosis, Dementia, POEMS and Autoimmune Encephalitis including Basal Ganglia Encephalitis. NICL is associated with the Wolfson Biomarker Laboratory (WBL) and the biomarker laboratory of the Leonard Wolfson Experimental Neurology Centre (LWENC) led by Henrik Zetterberg alongside whom neurofilament light chain measurement is currently being studied. NICL has close links with both the Dementia Research Centre and the NHNN neurosurgeons, collaborating on research into the clinical and prognostic uses of dementia biomarkers, respectively. The team collaborates closely with many of the neurologists based at NHNN to improve clinical care. NICL also provide an analytical service for congenital disorders of glycosylation (CDG) and have co-authored papers with GOSH and ICH researchers.
The clinical lead, Dr Michael Lunn, is leading several research studies into biomarkers such as VEGF and novel autoantibodies in inflammatory neuropathies, a diverse group of diseases including POEMS, Guillain-Barré syndrome and amyloidosis, many of which can result in profound, significant and frequently permanent disabilities when not treated promptly or appropriately. Biomarkers are needed to know when to treat. For example, paraproteinaemic neuropathies frequently require no treatment but in others the treatment may involve potentially toxic chemotherapy; POEMS syndrome is treated with autologous bone marrow transplantation but exactly when to treat is not known.
The laboratory has a developing research interest in mechanisms of autoimmune encephalitis (for example NMDA-R mediated encephalitides), headed up by Dr Mike Zandi. Retinal antibodies are also a key focus of the laboratory and we are developing our panel further in association with UCLH. Translational research into serum and CSF assays used by the NHS, both for UCLH and the UK is a key aim of the laboratory and we aim to extend our repertoire of autoantibody and biomarker tests for neurological disorders.
Autoimmune dysfunction of the basal ganglia has been implicated in Sydenham’s chorea, paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS), Tourette’s syndrome and in a wide spectrum of patients with complex movement disorders. These patients have circulating anti-basal ganglia antibodies (ABGAs). It has been proposed that these antibodies are induced in response to streptococcal infection and cross-react with antigenic determinants in the basal ganglia by the process of molecular mimicry. We have shown that the ABGAs from these patients recognise antigens of molecular weights 40, 45, 60 and 98kDa. Antigens have been purified (ammonium sulphate purification, 2-dimensional electrophoresis, ion exchange chromatography and hydrophobic interaction chromatography) and identified as aldolase C, non-neuronal and neuronal specific enolase, and pyruvate kinase M1, respectively. These are the neuronal isoforms of glycolytic enzymes and are found in both neuronal cytoplasm and membrane and some (enolase) are also expressed on the surface of streptococci.
NICL Publications 2012 to 2017
Craven C, Baudracco I, Zetterberg H, Lunn MPT, Chapman MD, Lakdawala N, Watkins LD, Toma AK. The predictive value of T-tau and AB1-42 levels in idiopathic normal pressure hydrocephalus. Acta Neurochir. 2017 9 September published online.
Kuhle J Nourbakhsh B, Grant D, Morant S, Barro C, Yaldizli Ö, Pelletier D, Giovannoni G, Waubant E, Gnanapavan S. Serum neurofilament is associated with progression of brain atrophy and disability in early MS. Neurology. 2017 Feb 28;88(9):826-831.
Schirmer L, Worthington V, Solloch U, Loleit V, Grummel V, Lakdawala N, Grant D, Wassmuth R, Schmidt AH, Gebhardt F, Andlauer TF, Sauter J, Berthele A, Lunn MP, Hemmer B. Higher frequencies of HLA DQB1*05:01 and anti-glycosphingolipid antibodies in a cluster of severe Guillain-Barré syndromeJ Neurol. 2016 Oct;263(10):2105-13.
Heywood WE, Bliss E, Mills P, Yuzugulen J, Carreno G, Clayton PT, Muntoni F, Worthington VC, Torelli S, Sebire NJ, Mills K, Grunewald S. Global serum glycoform profiling for the investigation of dystroglycanopathies & Congenital Disorders of Glycosylation. Mol Genet Metab Rep. 2016 17;7:55-62.
Paterson RW, Toombs J, Chapman MD, Nicholas JM, Heslegrave AJ, Slattery CF, Foulkes AJM, Clark CM, Lane CAS, Weston PSJ, Lunn MP, Fox NC, Zetterberg H, Schott JM. Do cerebrospinal fluid transfer methods affect measured amyloid b42, total tau and phosphorylated tau in clinical practice? Alzheimer’s and Dementia: Diagnosis, Assessment & Disease Monitoring 2015;1:380-384.
Gnanapavan S, Yousaf N, Heywood W, Grant D, Mills K, Chernajovsky Y, Keir G, Giovannoni G. Growth associated protein (GAP-43): cloning and the development of a sensitive ELISA for neurological disorders. J Neuroimmunol. 2014 Nov 15;276(1-2):18-23..
Kawagashira Y, Koike H, Ohyama K, Hashimoto R, Iijima M, Adachi H, Katsuno M, Chapman M, Lunn M, Sobue G. Axonal loss influences the response to rituximab treatment in neuropathy associated with IgM monoclonal gammopathy with anti-myelin associated glycoprotein antibody. J Neurol Sci 2014;348;67-73.
Birch K, Burrows G, Cruickshank A, Egner W, Holbrook I, Lewis E, McNeilly J, Patel D, Worthington V. Cerebrospinal fluid total protein cannot reliably distinguish true subarachnoid haemorrhage from other causes of raised cerebrospinal fluid net bilirubin and net oxyhaemoglobin absorbances.Ann Clin Biochem. 2014 Nov;51(Pt 6):657-61.
Gnanapavan S, Grant D, Morant S, Furby J, Hayton T, Teunissen CE, Leoni V, Marta M, Brenner R, Palace J, Miller DH, Kapoor R, Giovannoni G. Biomarker report from the phase II lamotrigine trial in secondary progressive MS - neurofilament as a surrogate of disease progression. PLoS One. 2013 Aug 1;8(8)
Gnanapavan S, Ho P, Heywood W, Jackson S, Grant D, Rantell K, Keir G, Mills K, Steinman L, Giovannoni G. Progression in multiple sclerosis is associated with low endogenous NCAM. J Neurochem. 2013 Jun;125(5):766-73
Toombs J, Paterson RW, Lunn MP, Nicholas JM, Fox NC, Chapman MD, Schott JM, Zetterberg H. Identification of an important potential confound in CSF AD studies: aliquot volume. Clin Chem Lab Med 2013;51(12);2311-17.
Heywood WE, Mills P, Grunewald S, Worthington V, Jaeken J, Carreno G, Lemonde H, Clayton PT, Mills K. A new method for the rapid diagnosis of protein N-linked congenital disorders of glycosylation. J Proteome Res. 2013 Jul 5;12(7):3471-9.
Gnanapavan S, Grant D, Pryce G, Jackson S, Baker D, Giovannoni G. Neurofilament a biomarker of neurodegeneration in autoimmune encephalomyelitis. Autoimmunity. 2012 Jun;45(4):298-303.