Highly sensitive optoelectrical biosensor for multiplex allergy diagnosis
BIOSENSORS & BIOELECTRONICS
Authors: Mas, Salvador; Badran, Ahmed A.; Juarez, Maria-Jose; Fernandez de Rojas, Dolores Hernandez; Morais, Sergi; Maquieira, Angel
Abstract
Compact multiplexed biosensors systems hold great potential for diagnosis of diseases where the detection of multiple biomarkers is required. Hypersensitivity Immunoglobulin E mediated syndromes are primary immunodeficiency disorders associated with sensitization to allergens. Assessing immunoglobulin E (IgE) sensitization to allergens is an important strategy for allergy diagnosis. Here, we report for the first time a reliable, flexible and cost-effective optoelectrical biosensor system for the simultaneous determination of total and allergen-specific IgE and IgG, antibodies using an immunogold-silver signal amplification method. The biosensor was constructed on a regular digital versatile disc (DVD) to immobilize a panel of 12 allergen extracts or pure proteins in microarray format, as a proof of concept. The multiplexed biosensor showed a limit of detection of 0.26 IU/mL (624 pg/mL) and 14 ng/mL for IgE and IgG antibodies, respectively. The system was successfully applied in a cohort of 127 human serum samples, showing good sensitivity (97.6%) as well as specificity (85.7%), and an excellent area under the curve (AUC) value was found at 0.977 (confidence interval, CI 0.957 to 0.990) as compared and validated with a reference clinical immunofluorescence assay, confirming an excellent correlation between both techniques. The multiplex biosensor system with on-demand panel composition can be used fully autonomously in clinical or mobile laboratory settings without the need for any additional medical equipment, with which could make it suitable for massive allergy screening campaigns to better define sensitization profiles.
Sex, age, and hospitalization drive antibody responses in a COVID-19 convalescent plasma donor population
JOURNAL OF CLINICAL INVESTIGATION
Authors: Klein, Sabra; Pekosz, Andrew; Park, Han-Sol; Ursin, Rebecca; Shapiro, Janna; Benner, Sarah; Littlefield, Kirsten; Kumar, Swetha; Naik, Harnish Mukesh; Betenbaugh, Michael; Shrestha, Ruchee; Wu, Annie; Hughes, Robert; Burgess, Imani; Caturegli, Patricio; Laeyendecker, Oliver; Quinn, Thomas; Sullivan, David; Shoham, Shmuel; Redd, Andrew; Bloch, Evan; Casadevall, Arturo; Tobian, Aaron
Abstract
Convalescent plasma is a leading treatment for coronavirus disease 2 019 (COVID-19), but there is a paucity of data identifying its therapeutic efficacy. Among 126 potential convalescent plasma donors, the humoral immune response was evaluated using a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus neutralization assay with Vero-E6-TMPRSS2 cells; a commercial IgG and IgA ELISA to detect the spike (S) protein S1 domain (EUROIMMUN); IgA, IgG, and IgM indirect ELISAs to detect the full-length S protein or S receptor-binding domain (S-RBD); and an IgG avidity assay. We used multiple linear regression and predictive models to assess the correlations between antibody responses and demographic and clinical characteristics. IgG titers were greater than either IgM or IgA titers for S1, full - length S, and S - RBD in the overall population. Of the 126 plasma samples, 101 (80%) had detectable neutralizing antibody (nAb) titers. Using nAb titers as the reference, the IgG ELISAs confirmed 95%-98% of the nAb-positive samples, but 20% 32% of the nAb-negative samples were still IgG ELISA positive. Male sex, older age, and hospitalization for COVID-19 were associated with increased antibody responses across the serological assays. There was substantial heterogeneity in the antibody response among potential convalescent plasma donors, but sex, age, and hospitalization emerged as factors that can be used to identify individuals with a high likelihood of having strong antiviral antibody responses.