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2017 Short-term Fellowship Report

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by Nesrin Reisli

Being awarded the ESID Short-term fellowship in 2017 allowed me to visit the group of Dr. Mirjam van der Burg at the Erasmus MC in Rotterdam, the Netherlands for one month between 29th May – 29th June 2017.

We worked on a collaborative project on the increased IgE in patients with PID and we will further continue.

Upon activation by antigen in peripheral lymphoid organs, mature B cells may undergo IgH class-switch recombination (CSR), a process  in which the IgHm constant region exons (Cm) are deleted and replaced by one of several sets of downstream CH exons (e.g., Cg, Ca, and Ce), termed CH genes. CSR is the basis for IgH switching from IgM to other Ig classes (e.g., IgG, IgE, or IgA). Based on studies in mice, it has been suggested that in certain immunodeficiencies IgE dysregulation may be related to impaired B cell maturation.1 In several PID, including Hyper IgE syndrome, Omenn Syndrome, WAS and IPEX, the elevated IgE levels have been attributed to T-cell dysregulation or dysfunction.2

In our collaborative project, we planned to explore in detail the relation between impaired B cell maturation and elevated IgE at a molecular level.

Initiated this studies by analysing the switch regions at the molecular level using PCR and sequencing analysis.

We had diagnosed a XLA patient with increased serum IgE levels. We would like to evaluate how these IgE molecules were produced. I studied on this patient with Bruton's Disease(XLA). XLA is the prototypic humoral immunodeficiency. Function-loss mutations in BTK lead to a block in B-cell maturation, a near total absence of B cells in the periphery, and agammaglobulinemia. Recurrent upper and lower respiratory tract infections, including otitis media, sinusitis, bronchitis, and pneumonia are common.

We included 3 patients with Hyper IgE Syndrome as additional PID with elevated IgE levels and we will also plan to include 3 Omenn Syndrome and 2 WAS patients.

In particular, I learned and performed different laboratory techniques including DNA isolation from PBMNC’s, PCR and Sanger sequencing,analysing the sequences of switch regions also I improved my practical skills in the laboratory during my stay.

Finally, I joined the weekly lab meetings and research meetings. I attended Center of Chronic Immunodeficiency’s 4th Workshop on Diagnostics of Immunodeficiencies in Freiburg, Germany on 19-21th June 2017 and presented a case under supervision of Dr. Mirjam van der Burg.

During my visit, the members of the lab of Dr. Mirjam van der Burg were very helpful and we had a good communication with all members. Their comments further improved my knowledge and skills.

I would like to thank to ESID for awarding me the ESID Short-term fellowship and supporting my visit to Rotterdam.This training has been very beneficial for me and also  helped me to make a decision for my future education plans. The stay was too short to finish the entire project, but it is was a good start of a project, which will be followed us as collaborative project between the centers in Konya and Rotterdam.

1.   Wesemann DR, Magee JM, Boboila C, Calado DP, Gallagher MP, Portuguese AJ, Manis JP, Zhou X, Recher M, Rajewsky K, Notarangelo LD, Alt FW. Immature B cells preferentially switch to IgE with increased direct Smu to Sepsilon recombination. J Exp Med. 2011;208:2733-2746.

2.   Ozcan E, Notarangelo LD, Geha RS. Primary immune deficiencies with aberrant IgE production. J Allergy Clin Immunol. 2008;122:1054-1062; quiz 1063-1054.