PhD Autoantibody formation in patients with TTP, Sanquin Research, Amsterdam
Ph.D. Student, Autoantibody formation in patients with TTP, Sanquin
Research, Amsterdam
Ph.D. Student, Research department of Plasma Proteins, Amsterdam
Plesmanlaan, 36 hours
The Research Group:
The research program of the Department of Plasma Proteins focuses on
the biology and function of blood coagulation factors that include Von
Willebrand factor (VWF) and ADAMTS13. A multidisciplinary approach
involving cell biological and immunological approaches is used within
the different lines of research. Recently, MHC class II tetramer
technology has established in our department in order to characterize
CD4+ T cell responses to blood coagulation factors in patients with
bleeding or thrombotic disorders.
Project:
Thrombotic thrombocytopenic purpura (TTP) is a microvascular occlusive
disorder that is characterized by systemic aggregation of platelets in
the brain, kidney and other organs. Systemic clumping of platelets is
due to a deficiency of the VWF cleaving protease ADAMTS13 which
results in accumulation of platelet-reactive ultra-large VWF multimers
in the circulation of patients with TTP. In the majority of patients
with TTP antibodies directed towards ADAMTS13 develop. Over the past
few years we have shown that B cell responses are directed towards a
single domain on ADAMTS13 that is crucial for its interaction with
VWF. At present we do not know why antibodies directed towards
ADAMTS13 develop in apparently healthy individuals. The triggering
events may comprise a foreign antigen such as a pathogen expressing a
T cell epitope resembling ADAMTS13 (molecular mimicry). Presently
ADAMTS13 specific CD4+ T cell responses in patients with acquired TTP
have not been defined. MHC class II tetramers will be used to analyse
CD4+ T cell responses at the clonal level in patients with acquired
TTP. The data evolving from these studies may provide a basis for
further improvement of therapeutic approaches for this thrombotic
disorder which will involve generation and administration of
tolerogenic antigen presenting cells or alternatively promote the
formation of regulatory T cells by targeting immunodominant T cell
epitopes to APC’s in vivo.
Additional information:
Luken BM, Turenhout EA, Hulstein JJ, van Mourik JA, Fijnheer R,
Voorberg J (2005) The spacer domain of ADAMTS13 contains a major
binding site for antibodies in patients with thrombotic
thrombocytopenic purpura. Thromb. Haemost. 93, 267-274.
Luken BM, Kaijen PH, Turenhout EA, Kremer-Hovinga JA, van Mourik JA,
Fijnheer R, Voorbegr J (2006) Multiple B-cell clones producing
antibodies directed to the spacer and disintegrin/thrombospondin
type-1 repeat 1 (TSP1) of ADAMTS13 in a patient with acquired
thrombotic thrombocytopenic purpura. J Thromb Haemost 4(11):2355-64.
Requested:
* university graduate;
* ample intellectual and experimental skills;
* a highly motivated candidate with expertise in cell biology
and/or immunology.
Offered:
* a temporary position as a Ph.D student for 4 years in a
challenging research environment;
* salary and conditions are conform CAO Sanquin.
Further information:
For further information please contact mr. dr. J.J. Voorberg, tel.
020-5123151 or by e-mail j.voorberg@sanquin.nl.
Your written application, accompanied with Curriculum Vitae, can be
addressed to the department Human Resource Management, attentions to
Ms T.M.E. Verduijn, PO Box 9190, 1006 AD Amsterdam or by e-mail
werk@sanquin.nl, under indication of job opening number TV 09-08. U
kunt ook solliciteren via het sollicitatieformulier (in Dutch)
