TY  - JOUR
A1  - Panayotova-Dimitrova, Diana
A1  - Feoktistova, Maria
A1  - Ploesser, Michaela
A1  - Kellert, Beate
A1  - Hupe, Mike
A1  - Horn, Sebastian
A1  - Makarov, Roman
A1  - Jensen, Federico
A1  - Porubsky, Stefan
A1  - Schmieder, Astrid
A1  - Zenclussen, Ana Claudia
A1  - Marx, Alexander
A1  - Kerstan, Andreas
A1  - Geserick, Peter
A1  - He, You-Wen
A1  - Leverkus, Martin
T1  - cFLIP Regulates Skin Homeostasis and Protects against TNF-Induced Keratinocyte Apoptosis
JF  - Cell Reports
N2  - FADD, caspase-8, and cFLIP regulate the outcome of cell death signaling. Mice that constitutively lack these molecules die at an early embryonic age, whereas tissue-specific constitutive deletion of FADD or caspase-8 results in inflammatory skin disease caused by increased necroptosis. The function of cFLIP in the skin in vivo is unknown. In contrast to tissue-specific caspase-8 knockout, we show that mice constitutively lacking cFLIP in the epidermis die around embryonic days 10 and 11. When cFLIP expression was abrogated in adult skin of cFLIP(fl/fl)-K14CreER(tam) mice, severe inflammation of the skin with concomitant caspase activation and apoptotic, but not necroptotic, cell death developed. Apoptosis was dependent of autocrine tumor necrosis factor production triggered by loss of cFLIP. In addition, epidermal cFLIP protein was lost in patients with severe drug reactions associated with epidermal apoptosis. Our data demonstrate the importance of cFLIP for the integrity of the epidermis and for silencing of spontaneous skin inflammation.
KW  - eczematous dermatitis
KW  - programmed necrosis
KW  - gene induction
KW  - in-vivo
KW  - activation
KW  - mediated apoptosis
KW  - c-flip
KW  - cell-death
KW  - Stevens-Johnson syndrome
KW  - toxic epidermal necrolysis
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-122155
VL  - 5
ER  - 
TY  - JOUR
A1  - Stoevesandt, Johanna
A1  - Hofmann, Bernd
A1  - Hain, Johannes
A1  - Kerstan, Andreas
A1  - Trautmann, Axel
T1  - Single venom-based immunotherapy effectively protects patients with double positive tests to honey bee and Vespula venom
JF  - Allergy, Asthma & Clinical Immunology
N2  - Background

Referring to individuals with reactivity to honey bee and Vespula venom in diagnostic tests, the umbrella terms “double sensitization” or “double positivity” cover patients with true clinical double allergy and those allergic to a single venom with asymptomatic sensitization to the other. There is no international consensus on whether immunotherapy regimens should generally include both venoms in double sensitized patients.

Objective

We investigated the long-term outcome of single venom-based immunotherapy with regard to potential risk factors for treatment failure and specifically compared the risk of relapse in mono sensitized and double sensitized patients.

Methods

Re-sting data were obtained from 635 patients who had completed at least 3 years of immunotherapy between 1988 and 2008. The adequate venom for immunotherapy was selected using an algorithm based on clinical details and the results of diagnostic tests.

Results

Of 635 patients, 351 (55.3%) were double sensitized to both venoms. The overall re-exposure rate to Hymenoptera stings during and after immunotherapy was 62.4%; the relapse rate was 7.1% (6.0% in mono sensitized, 7.8% in double sensitized patients). Recurring anaphylaxis was statistically less severe than the index sting reaction (P = 0.004). Double sensitization was not significantly related to relapsing anaphylaxis (P = 0.56), but there was a tendency towards an increased risk of relapse in a subgroup of patients with equal reactivity to both venoms in diagnostic tests (P = 0.15).

Conclusions

Single venom-based immunotherapy over 3 to 5 years effectively and long-lastingly protects the vast majority of both mono sensitized and double sensitized Hymenoptera venom allergic patients. Double venom immunotherapy is indicated in clinically double allergic patients reporting systemic reactions to stings of both Hymenoptera and in those with equal reactivity to both venoms in diagnostic tests who have not reliably identified the culprit stinging insect.
KW  - Anaphylaxis
KW  - Double sensitization
KW  - Field sting
KW  - Honey bee
KW  - Hymenoptera venom
KW  - Immunotherapy
KW  - Relapse
KW  - Risk factor
KW  - Treatment failure
KW  - Vespula
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96808
UR  - http://www.aacijournal.com/content/9/1/33
ER  -