TY  - JOUR
AU  - Lijfering, W.M.
AU  - Brouwer, J.L.P.
AU  - Veeger, N.J.
AU  - Bank, I.
AU  - Coppens, M.
AU  - Middeldorp, S.
AU  - Hamulyak, K.
AU  - Prins, M.H.
AU  - Buller, H.R.
AU  - Meer, J.W.M. van der
PY  - 2009
UR  - https://hdl.handle.net/2066/81593
AB  - Thrombophilia screening is controversial. In a retrospective family cohort, where probands had thrombosis and a thrombophilic defect, 2479 relatives were tested for thrombophilia. In antithrombin-, protein C-, and protein S-deficient relatives, annual incidences of venous thrombosis were 1.77% (95% CI, 1.14-2.60), 1.52% (95% CI, 1.06-2.11), and 1.90% (95% CI, 1.32-2.64), respectively, at a median age of 29 years and a positive family history of more than 20% symptomatic relatives. In relatives with factor V (FV) Leiden, prothrombin 20210G>A, or high FVIII levels, these were 0.49% (95% CI, 0.39-0.60), 0.34% (95% CI, 0.22-0.49), and 0.49% (95% CI, 0.41-0.51), respectively. High FIX, FXI, and TAFI, and hyperhomocysteinemia were not independent risk factors. Annual incidence of major bleeding in antithrombin-, protein C-, or protein S-deficient relatives on anticoagulants was 0.29% (95% CI, 0.03-1.04). Cumulative recurrence rates in relatives with antithrombin, protein C, or protein S deficiency were 19% at 2 years, 40% at 5 years, and 55% at 10 years. In relatives with FV Leiden, prothrombin 20210G>A, or high levels FVIII, these were 7%, 11%, and 25%, respectively. Considering its clinical implications, thrombophilia testing should address hereditary deficiencies of antithrombin, protein C, and protein S in patients with first venous thrombosis at young age and/or a strong family history of venous thrombosis.
TI  - Selective testing for thrombophilia in patients with first venous thrombosis: results from a retrospective family cohort study on absolute thrombotic risk for currently known thrombophilic defects in 2479 relatives.
EP  - 5322
SN  - 0006-4971
IS  - iss. 21
SP  - 5314
JF  - Blood
VL  - vol. 113
DO  - https://doi.org/10.1182/blood-2008-10-184879
ER  - 
TY  - JOUR
AU  - Netea, M.G.
AU  - Nold-Petry, C.A.
AU  - Nold, M.F.
AU  - Joosten, L.A.B.
AU  - Opitz, B.
AU  - Meer, J.H. van der
AU  - Veerdonk, F.L. van de
AU  - Ferwerda, G.
AU  - Heinhuis, S.M.
AU  - Devesa, I.
AU  - Funk, C.J.
AU  - Mason, R.J.
AU  - Kullberg, B.J.
AU  - Rubartelli, A.
AU  - Meer, J.W.M. van der
AU  - Dinarello, C.A.
PY  - 2009
UR  - https://hdl.handle.net/2066/80484
AB  - The processing of pro-interleukin-1beta depends on activation of caspase-1. Controversy has arisen whether Toll-like receptor (TLR) ligands alone can activate caspase-1 for release of interleukin-1beta (IL-1beta). Here we demonstrate that human blood monocytes release processed IL-1beta after a one-time stimulation with either TLR2 or TLR4 ligands, resulting from constitutively activated caspase-1 and release of endogenous adenosine triphosphate. The constitutive activation of caspase-1 depends on the inflammasome components, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and NALP3, but in monocytes caspase-1 activation is uncoupled from pathogen-associated molecular pattern recognition. In contrast, macrophages are unable to process and release IL-1beta solely by TLR ligands and require a second adenosine triphosphate stimulation. We conclude that IL-1beta production is differentially regulated in monocytes and macrophages, and this reflects their separate functions in host defense and inflammation.
TI  - Differential requirement for the activation of the inflammasome for processing and release of IL-1beta in monocytes and macrophages.
EP  - 2335
SN  - 0006-4971
IS  - iss. 10
SP  - 2324
JF  - Blood
VL  - vol. 113
DO  - https://doi.org/10.1182/blood-2008-03-146720
ER  - 
TY  - JOUR
AU  - Bodar, E.J.
AU  - Hilst, J.C.H. van der
AU  - Heerde, W.L. van
AU  - Meer, J.W.M. van der
AU  - Drenth, J.P.H.
AU  - Simon, A.
PY  - 2007
UR  - https://hdl.handle.net/2066/51966
AB  - 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.
TI  - Defective apoptosis of peripheral-blood lymphocytes in hyper-IgD and periodic fever syndrome.
EP  - 2418
SN  - 0006-4971
IS  - iss. 6
SP  - 2416
JF  - Blood
VL  - vol. 109
DO  - https://doi.org/10.1182/blood-2005-10-039578
ER  - 
TY  - JOUR
AU  - Sprong, T.
AU  - Brandtzaeg, P.
AU  - Fung, M.
AU  - Pharo, A.M.
AU  - Hoiby, E.A.
AU  - Michaelsen, T.E.
AU  - Aase, A.
AU  - Meer, J.W.M. van der
AU  - Deuren, M. van
AU  - Molines, T.E.
PY  - 2003
UR  - https://hdl.handle.net/2066/19740
PB  - Amer soc hematology
TI  - Inhibition of C5a-induced inflammation with preserved C5b-9-mediated bactericidal activity in a human whole blood model of meningococcal sepsis
EP  - 3710
SN  - 0006-4971
IS  - iss. 10
SP  - 3702
JF  - Blood
VL  - vol. 102
ER  -