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 Blood, 15 March 2007, Vol. 109, No. 6, pp. 2416-2418.
Prepublished online as a Blood First Edition Paper on November 30, 2006; DOI 10.1182/blood-2005-10-039578.

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Submitted October 26, 2005
Accepted August 16, 2006

Defective apoptosis of peripheral blood lymphocytes in hyper-IgD and periodic fever syndrome

Evelien J. Bodar*, Jeroen C.H. van der Hilst, Waander van Heerde, Jos W.M. van der Meer, Joost P.H. Drenth, and Anna Simon

Dept of General Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
Dept of Haematology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
Dept of Gastroenterology & Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands

* Corresponding author; email: e.bodar{at}aig.umcn.nl.

Hereditary periodic fever syndromes are characterized by incapacitating attacks of fever and generalized inflammation. While the mutated genes for the major syndromes in this group are known, the pathogenesis remains unclear. Aim of this study was to investigate apoptosis in periodic fever patients as a possible pathogenic factor. We measured anisomycin-induced apoptosis with annexin-V flowcytometry and caspase 3/7 activity in peripheral blood lymphocytes from symptom-free patients with HIDS (n=10), TRAPS (n=7) and FMF (n=2). HIDS lymphocytes showed a decreased percentage of apoptosis during remission compared to controls by both methods (17.8 vs 55.4%), whereas no difference was observed in TRAPS or FMF lymphocytes. This defective apoptosis of lymphocytes may be a central pathogenic mechanism in HIDS since dysfunction of one of the inhibitory mechanisms to curtail the immunological response could cause an unbridled generalized inflammation after a trivial stimulus.


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