Defective apoptosis of peripheral-blood lymphocytes in hyper-IgD and periodic fever syndrome.
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. The aim of this study was to investigate apoptosis in patients with periodic fever as a possible pathogenic factor. We measured anisomycin-induced apoptosis with annexin-V flow cytometry and caspase-3/7 activity in peripheral-blood lymphocytes from symptom-free patients with hyper-IgD and periodic fever syndrome (HIDS; n = 10), TNF-receptor-associated periodic syndrome (TRAPS; n = 7), and familial Mediterranean fever (FMF; n = 2). HIDS lymphocytes showed a decreased percentage of apoptosis during remission by both methods compared with controls (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 immunologic response could cause an unbridled generalized inflammation after a trivial stimulus.
Bodar
Evelien J
EJ
Department of General Internal Medicine, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands. e.bodar@aig.umcn.nl
van der Hilst
Jeroen C H
JC
van Heerde
Waander
W
van der Meer
Jos W M
JW
Drenth
Joost P H
JP
Simon
Anna
A
D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D010505:Familial Mediterranean Fever / Q000276:immunology* / Q000473:pathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007072:Immunoglobulin D / Q000276:immunology*; D008214:Lymphocytes / Q000166:cytology* / Q000276:immunology*; D008297:Male
D007072:Immunoglobulin D