FVIII-Epitope Mapping (Lumitope) and Platelet disorders- PD Dr. B. Pezeshkpoor

Approximately 30% of patients with hemophilia A develop inhibitory antibodies to coagulation factor VIII. Antibody formation is both the most serious and the most expensive complication of hemophilia. At our institute, these antibodies are readily detected using the Bethesda assay and an ELISA, so that a determination can be made as to whether the patient is positive and what the titer is. In the Lumitope project, the aim is to determine the antibody specificity, i.e. against which exact part (epitopes) of FVIII an antibody is directed. This provides information about the frequency of different antibodies against specific epitopes, as well as the possibility of developing a therapy.

Platelet biogenesis is a complex process that relies on the expression and functionality of a number of genes. To date, many different genes have been described to play a role in the synthesis and maturation of megacryocytes into functional platelets. Nevertheless, the cause of the disruption of functionality or the reduction in the number of platelets in half of all congenital cases with thrombocytopenia (reduction in the number of platelets) or thrombocytopathy (disruption of platelet functionality) cannot be elucidated. After the generation of induced pluripotent stem cells (iPS) from the blood of patients with thrombocytopenia, they are differentiated into megakaryocytes to study platelet biogenesis.

Ann-Cristin Berkemeier Rath (Technical assistant/WHK)
Nadja Sereda (Master student)

Link to the publications of the group: https://pubmed.ncbi.nlm.nih.gov/?term=behnaz+Pezeshkpoor

Selected Publications

1. Preisler B*, Pezeshkpoor B*, Banchev A, Fischer R, Zieger B, Scholz U, Rühl H, Kemkes-Matthes B, Schmitt U, Redlich A, Unal S, Laws HJ, Olivieri M, Oldenburg J, Pavlova A. Familial Multiple Coagulation Factor Deficiencies (FMCFDs) in a Large Cohort of Patients-A Single-Center Experience in Genetic Diagnosis. J Clin Med. 2021 Jan 18;10(2):347. doi: 10.3390/jcm10020347.
2. Jankowska KI, McGill J, Pezeshkpoor B, Oldenburg J, Atreya CD, Sauna ZE. Clinical manifestation of hemophilia A in the absence of mutations in the F8 gene that encodes FVIII: role of microRNAs. Transfusion. 2020 Feb;60(2):401-413. doi: 10.1111/trf.15605. Epub 2019 Nov 29. PMID: 31785023.
3. B. Pezeshkpoor, M. Gazorpak,A-C. Berkemeier, Singer H., Pavlova A., Biswas A. and J. Oldenburg In-silico and in-vitro evaluation of the impact of mutations in non-severe haemophilia A patients on assays discrepancies. Ann Hematol (2019). https://doi.org/10.1007/s00277-019-03691-1
4. Pezeshkpoor B, Czogalla KJ, Caspers M, Berkemeier AC, Liphardt K, Ghosh S, Kellner M, Ulrich S, Pavlova A, Oldenburg J. Variants in FIX propeptide associated with  Vitamin K antagonist hypersensitivity: functional analysis and additional data confirming the common founder mutations. Ann Hematol. 2018 Jun;97(6):1061-1069.
5. Pezeshkpoor B, Schreck U, Biswas A, Driesen J, Berkemeier AC, Pavlova A, Müller J, Oldenburg J. An in silico and in vitro approach to elucidate the impact of residues flanking the cleavage scissile bonds of FVIII. PLoS One. 2017 Jul 6;12(7):e0180456.
6. Pezeshkpoor B, Castoldi E, Mahler A, Hanel D, Müller J, Hamedani NS, Biswas A, Oldenburg J, Pavlova A. Identification and functional characterization of a novel F5 mutation (Ala512Val, FVBonn ) associated with activated protein C resistance. J Thromb Haemost. 2016 Jul;14(7):1353-63.
7. Pezeshkpoor B, Berkemeier AC, Czogalla KJ, Oldenburg J, El-Maarri O. Evidence of pathogenicity of a mutation in 3' untranslated region causing mild haemophilia A. Haemophilia. 2016 Jul;22(4):598-603.
8. Pezeshkpoor B, Theophilus BD, Guilliatt AM, Oldenburg J, Williams MD, El-Maarri O. Novel characterization of a breakpoint in F8: an individualized approach to gene analysis when PCR and MLPA results contradict. Haemophilia. 2015 May;21(3):392-7.
9. Pezeshkpoor B, Zimmer N, Marquardt N, Nanda I, Haaf T, Budde U, Oldenburg J,  El-Maarri O. Deep intronic 'mutations' cause hemophilia A: application of next generation sequencing in patients without detectable mutation in F8 cDNA. J Thromb Haemost. 2013 Sep;11(9):1679-87.
10. Pezeshkpoor B, Rost S, Oldenburg J, El-Maarri O. Identification of a third rearrangement at Xq28 that causes severe hemophilia A as a result of homologous recombination between inverted repeats. J Thromb Haemost. 2012 Aug;10(8):1600-8.  
11. Pezeshkpoor B, Oldenburg J. F8 gene: embedded in a region of genomic instability representing a hotspot of complex rearrangements. Haemophilia. 2015 Jul;21(4):513-5.
12. Pezeshkpoor B, Pavlova A, Oldenburg J, El-Maarri O. F8 genetic analysis strategies when standard approaches fail. Hamostaseologie. 2014;34(2):167-73.