Genetic biomarkers associated with IVIg treatment response or dependency in CIDP

Not all chronic inflammatory demyelinating polyneuropathy (CIDP) patients respond to IV immunoglobulin (IVIg) and it is not known why some patients need only one or two courses whilst others need long term treatment. Biomarkers are needed to predict response or duration of treatment to give more individualized treatment. We aim to investigate genetic factors associated with IVIg response or treatment dependency. We have collected DNA from at least 84 CIDP patients.  Most patients have been followed for a long time. Of these 84 patients, 65 were IVIg responsive whereas the other 19 patients did not respond significantly. From the 65 responders; 9 patients needed IVIg for ≤ 6 months. The following genetic biomarkers will be analyzed: TAG-1,  FcRn, GJB1 , FcyRIIB, SH2D2A, PRF1. We aim to find more insight into genetic factors that contribute to the response to IVIg. This will help us to understand why some CIDP patients respond better to IVIg than others and why some require long term treatment. This may also improve the understanding of the working mechanism of IVIg. 

Curriculum Vitae

Krista Kuitwaard was born on September 30th in Alkmaar, the Netherlands. She studied medicine at the Free University (VU) in Amsterdam. After obtaining her medical degree in 2003 she worked for 1 year at the Department of Neurology of the Medical Centre in Alkmaar (MCA). Therafter she worked as a neurology resident in the Erasmus Medical Centre (Erasmus MC) in Rotterdam.

She started her neurology training in 2005 at the Erasmus MC. Parallel to this residency she started her PhD research (The spectrum of GBS, CIDP and its IVIg treatment) under supervision of Prof. P.A. van Doorn. She received the C.U. Ariëns Kappers prize for the best neurology-related publication from the Dutch Neurological Society (NVvN) for her paper: Pharmacokinetics of intravenous immunoglobulin and outcome in Guillain-Barré syndrome (Ann Neurol 2009). She was awarded the PJ Dyck award at the Peripheral Nerve Society in Sydney in 2010 for her research on identifying factors related to a favourable response to IVIg in CIDP.

After completing her neurology residency she worked for 10 months as a neurologist and clinical neurophysiologist in the Erasmus MC. Since May 2014 she works as a neurologist with a special interest in neuromuscular disorders and clinical neurophysiology in the Albert Schweitzer hospital in Dordrecht. She still works for one day a week as a researcher in the Erasmus MC. Currently she is busy finishing her PhD project and setting up a dose finding trial of IVIg in CIDP patients. 

Publications

1. K Kuitwaard, AF Hahn, M Vermeulen, SL Venance, PA van Doorn. Intravenous immunoglobulin response in treatment-naïve chronic inflammatory demyelinating polyradiculoneuropathy. J Neurol Neurosurg Psychiatry 2014;doi:10.1136/jnnp-2014-309042
2. WJ Fokkink, MH Selman, JR Dortland, B Durmus, K Kuitwaard, R Huizinga, W van Rijs, AP Tio-Gillen, PA van Doorn, AM Deelder, M Wuhrer, BC Jacobs. IgG Fc N-glycosylation in Guillain-Barré syndrome treated with immunoglobulins. J Proteome Res 2014;13:1722-30
3. K Kuitwaard, PA van Doorn, M Vermeulen, LH van den Berg, E Brusse, AJ van der Kooi, WL van der Pol, IN van Schaik, NC Notermans, AP Tio-Gillen, W van Rijs, T van Gelder, BC Jacobs. Serum IgG levels in IV immunoglobulin treated chronic inflammatory demyelinating polyneuropathy J Neurol Neurosurg Psychiatry 2013;84:859-61
4. PA van Doorn, K Kuitwaard, BC Jacobs. Serum IgG levels as biomarkers for optimizing IVIg therapy in CIDP. J Peripher Nerv Syst 2011;16:38-40
5. SI van Nes, EK Vanhoutte, PA van Doorn, M Hermans, M Bakkers, K Kuitwaard, CG Faber, IS Merkies. Rasch-built Overall Disability Scale (R-ODS) for immune-mediated peripheral neuropathies. Neurology 2011;76:337-45
6. K Kuitwaard, LH van den Berg, M Vermeulen, E Brusse, EA Cats, AJ van der Kooi, NC Notermans, WL van der Pol, IN van Schaik, SI van Nes, WC Hop, PA van Doorn. Randomised controlled trial comparing two different immunoglobulins in chronic inflammatory demyelinating polyradiculoneuropathy. J Neurol Neurosurg Psychiatry 2010; 81:1374-9
7. BC Jacobs, C Walgaard, J Drenthen, K Kuitwaard, SI van Nes, PA van Doorn. Wel of niet vaccineren tegen het nieuwe influenza A (H1N1)-virus bij het syndroom van Guillain-Barré en CIDP? Tijdschr Neurol Neurochir 2010;111:17-9
8. PA van Doorn, K Kuitwaard, C Walgaard, R van Koningsveld, L Ruts, BC Jacobs. IVIG treatment and prognosis in Guillain-Barré syndrome. J Clin Immunol 2010;30:S74-8
9. K Kuitwaard, ME Bos-Eyssen, PH Blomkwist-Markens, PA van Doorn. Recurrences, vaccinations and long-term symptoms in GBS and CIDP. J Peripher Nerv Syst 2009;14:310-5
10. K Kuitwaard, J de Gelder, AP Tio-Gillen, WC Hop, T van Gelder, AW van Toorenenbergen, PA van Doorn, BC Jacobs. Pharmacokinetics of intravenous immunoglobulin and outcome in Guillain-Barré syndrome. Ann Neurol 2009;69:597-603
11. K Kuitwaard, PA van Doorn. Newer therapeutic options for chronic inflammatory demyelinating polyradiculoneuropathy. (review) Drugs 2009;69:987-1001
12. K Kuitwaard, WL van der Pol, L Ruts, PA van Doorn. Individual patients who experienced both Guillain-Barré syndrome and CIDP. J Peripher Nerv Syst 2009;14:66-8
13. K Kuitwaard, R van Koningsveld, L Ruts, BC Jacobs, PA van Doorn. Recurrent Guillain-Barré syndrome. J Neurol Neurosurg Psychiatry 2009;80:56-9
14. K Kuitwaard, HZ Flach, F van Kooten. Dubbelzijdige A.-vertebralisdissectie tijdens chiropraxiebehandeling. Ned Tijschr Geneeskd 2008;152:2464-9
15. K Kuitwaard, D Naafs, K Haasnoot, R ten Houten. Een jongen van 15 maanden met een herseninfarct. Tijdschr Kindergeneeskunde 2005;73:80-5
16. K Kuitwaard, R ten Houten. Pijn en "meningeale" prikkeling als eerste presentatie van het syndroom van Guillain-Barré. Tijdschr Neurol Neurochir 2005;106:17-20
17. K Kuitwaard, WP Vandertop. A patient with an odontoid fracture and atrophy of the tongue: a case report and systematic review of the literature. Surg Neurol 2005;64:525-32