Quantity increase and functional affinity/avidity decrease of anti-FcεRI and anti-IgE autoantibodies in chronic spontaneous urticaria.

Summary: Background. Patients with autoimmune forms of chronic spontaneous urticaria (aiCSU) exhibit autoantibodies against the high-affinity IgE receptor (FcεRI) and IgE. As the presence of these autoantibodies does not correlate with disease activity, the functional affinity/avidity may be relevant in aiCSU. This exploratory study aimed to characterize the quantity and avidity of autoantibodies against IgE and FcεRI over 6 months. Methods. The serum of 49 patients with CSU and 30 healthy control subjects was obtained at baseline and 6 months. Serum was analyzed by ELISA, to determine the quantity and avidity of anti-IgE and anti-FcεRI autoantibodies, and by basophil activation test (CU-BAT). Results. An increase in the quantity of anti-FcεRI and anti-IgE antibodies and a simultaneous decrease in avidity was found in all patients with CSU after 6 months: median anti-IgE increased from 6.7 ng/mL (IQR 5.1-12.5) to 23.8 ng/mL (IQR 12.3-121.5), p less than 0.001, median anti-FcεRI from 52.4 ng/mL (IQR 26.3-111.4) to 129.5 ng/mL (IQR 73.7-253.7), p less than 0.001. Median anti-IgE avidity decreased from 75.8% (IQR 55.3-90.8) to 56.4% (IQR 30.6-76.2), p=0.019 and median anti-FcεRI avidity from 75.1% (IQR 49.8-90.0) to 52.2 (IQR 38.2-60.1), p less than 0.001. In contrast, the frequency of activated basophils did not change significantly over time. Surprisingly, autoantibody avidity did not correlate with basophil activation. Conclusions. Both the quantity and avidity of anti-FcεRI and anti-IgE antibodies change over time, demonstrating that the CU-BAT is more suitable to diagnose aiCSU. In addition, the avidity of anti-FcεRI and anti-IgE antibodies do not correlate with CU-BAT and disease activity, suggesting that further factors independent of anti-FcεRI and anti-IgE autoantibodies contribute to aiCSU.

Prediction of short-term prognosis in elderly patients with acute pulmonary embolism: validation of the RIETE score.

Essentials The RIETE score was derived to predict 10-day adverse outcomes in acute pulmonary embolism (PE). We externally validated the RIETE score in a prospective cohort of patients with PE. The RIETE score classified fewer patients as low-risk than currently recommended scores. The RIETE score was not superior to other scores in predicting 10-day adverse outcomes. SUMMARY: Introduction The Registro Informatizado de la Enfermedad TromboEmbolica (RIETE) score was derived to identify patients with pulmonary embolism (PE) at low risk of overall complications. Objective To externally validate the RIETE score and compare its prognostic performance with the Pulmonary Embolism Severity Index (PESI), its simplified version (sPESI) and the Geneva Prognostic Score (GPS). Methods In a prospective multicenter cohort, we studied 687 elderly patients with acute PE. The primary outcome was 10-day overall complications (death, recurrent PE or major bleeding); the secondary outcome was 30-day overall mortality. We compared complications and mortality in low-risk vs. higher-risk patients and the area under the receiver operating characteristic (ROC) curve across scores. Results Overall, 27 patients (3.9%) had complications within 10 days and 22 (3.2%) died within 30 days. The RIETE score classified a smaller proportion of patients as low risk (31%) than the PESI (35%), sPESI (36%) and the GPS (90%). The proportion of low-risk patients based on the RIETE score, PESI, sPESI and GPS who had complications was 1.9%, 1.7%, 1.6% and 2.9%, respectively. The RIETE score had a lower area under the ROC curve (0.60) for predicting complications than the PESI (0.67), sPESI (0.65) and GPS (0.72). The area under the ROC curve for predicting mortality was similar (0.76-0.78) for all scores. Conclusion The RIETE score classified fewer patients as low risk than the other scores. It accurately identified patients at low risk of mortality but was not superior to other scores in predicting 10-day overall complications. TRIAL REGISTRATION: http://clinicaltrials.gov. Identifier: NCT00973596.

Double-blind placebo-controlled trial of the effect of omalizumab on basophils in chronic urticaria patients.

BACKGROUND: Omalizumab has been shown to be effective in treating chronic spontaneous urticaria (CSU). The reduction in FcεRI receptor density on the surface of basophils and mast cells is thought to play a major role in its effectiveness. We conducted a double-blind, randomized, placebo-controlled trial to investigate the mode of action of omalizumab in patients with antihistamine-resistant CSU. METHODS: Thirty patients were randomized in a 2:1 ratio to receive either 300 mg omalizumab or placebo. Four monthly applications of omalizumab/placebo were followed up with a visit 2 months after the last injection. The primary endpoint was the FcεRI receptor density change on basophils. RESULTS: Omalizumab led to a significant reduction in FcεRI receptor density on basophils as soon as 1 week after the first injection: baseline omalizumab vs placebo group, 80.31 ± 47.18 × 10³ vs 78.29 ± 45.09 × 10³ receptors/basophil ± SD; 1 week, 72.89 ± 47.79 × 10³ vs 27.83 ± 20.87 × 10³, P = .001. This effect continued during the treatment phase and persisted for 2 months after the last injection: 93.81 ± 56.50 × 10³ vs 21.09 ± 15.23 × 10³, P = .002. Values for basophil "releasability" and the basophil activation test (CU-BAT) of patient serum using donor basophils were unchanged despite treatment: CU-BAT, CD63 10.75% (7.35) in the placebo group vs 8.35% (15.20) in the omalizumab group, P = .778. CONCLUSION: We demonstrated a rapid reduction of FcεRI receptor density on basophils following treatment with omalizumab. Because CU-BAT using well-characterized, omalizumab-naïve donor basophils did not change during the treatment phase, autoreactive serum factors seem to remain unaltered. This points towards a cellular effect of omalizumab on basophils. To predict the omalizumab response time and to monitor disease, FcεRI density and CU-BAT might be promising cellular-based assays.

Frequency of use and acceptability of clinical prediction rules for pulmonary embolism among Swiss general internal medicine residents.

INTRODUCTION: Whether clinical prediction rules for pulmonary embolism are accepted and used among general internal medicine residents remains uncertain. We therefore evaluated the frequency of use and acceptability of the Revised Geneva Score (RGS) and the Pulmonary Embolism Severity Index (PESI), and explored which factors were associated with rule use. MATERIALS/METHODS: In an online survey among general internal medicine residents from 10 Swiss hospitals, we assessed rule acceptability using the Ottawa Acceptability of Decision Rules Instrument (OADRI) and explored the association between physician and training-related factors and rule use using mixed logistic regression models. RESULTS: The response rate was 50.4% (433/859). Overall, 61% and 36% of the residents reported that they always or regularly use the RGS and the PESI, respectively. The mean overall OADRI score was 4.3 (scale 0-6) for the RGS and 4.1 for the PESI, indicating a good acceptability. Rule acceptability (odds ratio [OR] 6.19 per point, 95% confidence interval [CI] 3.64-10.51), prior training in emergency medicine (OR 5.14, CI 2.20-12.01), and availability of internal guidelines recommending RGS use (OR 4.25, CI 2.15-8.43) were associated with RGS use. Rule acceptability (OR 6.43 per point, CI 4.17-9.92) and rule taught at medical school (OR 2.06, CI 1.24-3.43) were associated with PESI use. CONCLUSIONS: The RGS was more frequently used than the PESI. Both rules were considered acceptable. Rule acceptability, prior training in emergency medicine, availability of internal guidelines, and rule taught at medical school were associated with rule use and represent potential targets for quality improvement interventions.