Long-Term Follow-Up of Children after Venom Immunotherapy: Low Adherence to Anaphylaxis Guidelines.

BACKGROUND: Data on the long-term outcome of children after specific venom immunotherapy (VIT) are limited. Therefore, we assessed sting recurrence and anaphylaxis relapse rates as well as adherence to anaphylaxis guidelines with regard to the availability of emergency equipment and education status. METHODS: For this long-term survey, data of 311 children with a history of anaphylactic reactions to hymenoptera stings were collected by chart review. We included patients who were treated with a 3-year VIT between 1993 and 2009 and had completed a questionnaire. RESULTS: Forty of the 311 patients were included. Mean VIT duration was 3.1 years. Of the 40 patients included, 29 children (72.5%) received VIT with vespid venom, 9 with bee venom, and 2 patients with both venoms. During a mean follow-up period of 13 years, 20/40 patients (50%) suffered re-stings. Six of the 20 (30%) patients developed again anaphylactic symptoms (grade 1 n = 5, grade 3 n = 1); 2 were allergic to vespid and 4 to bee venom. Of the entire cohort, only 5/40 (12.5%) had appropriate emergency kits according to the guidelines of the European Academy of Allergy and Clinical Immunology. Among the patients who had emergency kits available, one third (5/15) felt uncertain about the correct application of the medication. Less than two thirds of our population (25/40) affirmed that they have been educated in emergency management. The vast majority (95%; 38/40) of our patients did not have allergy follow-ups after VIT completion. CONCLUSIONS: Anaphylactic relapses are not uncommon, and there are considerable deficits in the emergency management of patients. Hence, comprehensive standardized anaphylaxis education programs as well as regular follow-ups of the allergy status are crucial.

Expression of the actin stress fiber-associated protein CLP36 in the human placenta.

Differentiation processes in the trophoblast comprise polarization, cell fusion and migration. All these processes involve dramatic reorganizations of cytoskeletal proteins such as intermediate filaments or actin. Due to very restricted knowledge on cytoskeletal changes in trophoblast, we analyzed the protein expression of an actin stress fiber-associated protein, the carboxy-terminal LIM domain protein (CLP36). CLP36 belongs to the enigma family of proteins, binds to alpha-actinin and is involved in the cytoskeletal reorganization and signal transduction of a variety of cells. CLP36 protein was found to be exclusively expressed in the cytotrophoblast layer. Colocalization of CLP36 with Mib-1 revealed that CLP36 protein expression is restricted to proliferative and early post-proliferative trophoblast cells. Blockage of syncytial fusion by culture of villous explants in the presence of caspase 8 inhibitors further supported this notion since CLP36 was only found in the basal and proliferative layer of the multilayered cytotrophoblast. We present evidence for the exclusive protein expression of CLP36 in proliferative and early post-proliferative trophoblast cells. Pathological pregnancy syndromes such as preeclampsia are driven by alterations of trophoblast differentiation and turnover, where it needs to be elucidated whether CLP36 is involved in these alterations.

Concerted upregulation of CLP36 and smooth muscle actin protein expression in human endometrium during decidualization.

The human endometrium prepares for implantation of the blastocyst by reorganization of its whole cellular network. Endometrial stroma cells change their phenotype starting around the 23rd day of the menstrual cycle. These predecidual stroma cells first appear next to spiral arteries, and after implantation these cells further differentiate into decidual stroma cells. The phenotypical changes in these cells during decidualization are characterized by distinct changes in the actin filaments and filament-related proteins such as alpha-actinin. The carboxy-terminal LIM domain protein with a molecular weight of 36 kDa (CLP36) is a cytoskeletal component that has been shown to associate with contractile actin filaments and to bind to alpha-actinin supporting a role for CLP36 in cytoskeletal reorganization and signal transduction by binding to signaling proteins. The expression patterns of CLP36, alpha-actinin and actin were studied in endometrial stroma cells from different stages of the menstrual cycle and in decidual stroma cells from the 6th week of gestation until the end of pregnancy. During the menstrual cycle, CLP36 is only expressed in the luminal and glandular epithelium but not in endometrial stroma cells. During decidualization and throughout pregnancy, a parallel upregulation of CLP36 and smooth muscle actin, an early marker of decidualization in the baboon, was observed in endometrial decidual cells. Since both proteins maintain a high expression level throughout pregnancy, a role of both proteins is suggested in the stabilization of the cytoskeleton of these cells that come into close contact with invading trophoblast cells.