Browsing by Author "Rey, Emma"
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Publication A Third Dose of SARS-CoV-2 mRNA Vaccine Improves Immune Response in Chronic Kidney Disease Patients(2023) Poli Harlowe, María Cecilia; Vial Cox, María Cecilia; Rey, Emma; González, Natalia; Cortés, Lina; Hormazabal, Juan; Ramírez, Carolina; De la Cruz, Javiera; Ulloa, CamiloChronic kidney disease (CKD) patients have an increased risk of morbidity and mortality following SARS-CoV-2 infection. Vaccination in these patients is prioritized, and monitoring of the immune response is paramount to define further vaccination strategies. This prospective study included a cohort of 100 adult CKD patients: 48 with kidney transplant (KT) and 52 on hemodialysis without prior COVID-19. The patients were assessed for humoral and cellular immune responses after four months of an anti-SARS-CoV-2 primary two-dose vaccination scheme (CoronaVac or BNT162b2) and one month after a booster third dose of BNT162b2 vaccine. We identified poor cellular and humoral immune responses in the CKD patients after a primary vaccination scheme, and these responses were improved by a booster. Robust polyfunctional CD4+ T cell responses were observed in the KT patients after a booster, and this could be attributed to a higher proportion of the patients having been vaccinated with homologous BNT162b2 schemes. However, even after the booster, the KT patients exhibited lower neutralizing antibodies, attributable to specific immunosuppressive treatments. Four patients suffered severe COVID-19 despite three-dose vaccination, and all had low polyfunctional T-cell responses, underscoring the importance of this functional subset in viral protection. In conclusion, a booster dose of SARS-CoV-2 mRNA vaccine in CKD patients improves the impaired humoral and cellular immune responses observed after a primary vaccination scheme.Publication Autoantibodies Against Proteins Previously Associated With Autoimmunity in Adult and Pediatric Patients With COVID-19 and Children With MIS-C(2022) Burbelo, Peter; Castagnoli, Riccardo; Shimizu, Chisato; Delmonte, Ottavia; Dobbs, Kerry; Discepolo, Valentina; Lo Vecchio, Andrea; Guarino, Alfredo; Licciardi, Francesco; Ramenghi, Ugo; Rey, Emma; Vial, Cecilia; Marseglia, Gian; Licari, Amelia; Montagna, Daniela; Rossi, Camillo; Montealegre, Gina; Barron, Karyl; Warner, Blake; Chiorini, John; Espinosa, Yazmin; Noguera, Loreani; Dropulic, Lesia; Truong, Meng; Gerstbacher, Dana; Mató, Sayonara; Kanegaye, John; Tremoulet, Adriana; Pediatric Emergency Medicine Kawasaki Group; Eisenstein, Eli; Su, Helen; Imberti, Luisa; Poli, Cecilia; Burns, Jane; Notarangelo, Luigi; Cohen, JeffreyThe antibody profile against autoantigens previously associated with autoimmune diseases and other human proteins in patients with COVID-19 or multisystem inflammatory syndrome in children (MIS-C) remains poorly defined. Here we show that 30% of adults with COVID-19 had autoantibodies against the lung antigen KCNRG, and 34% had antibodies to the SLE-associated Smith-D3 protein. Children with COVID-19 rarely had autoantibodies; one of 59 children had GAD65 autoantibodies associated with acute onset of insulin-dependent diabetes. While autoantibodies associated with SLE/Sjögren's syndrome (Ro52, Ro60, and La) and/or autoimmune gastritis (gastric ATPase) were detected in 74% (40/54) of MIS-C patients, further analysis of these patients and of children with Kawasaki disease (KD), showed that the administration of intravenous immunoglobulin (IVIG) was largely responsible for detection of these autoantibodies in both groups of patients. Monitoring in vivo decay of the autoantibodies in MIS-C children showed that the IVIG-derived Ro52, Ro60, and La autoantibodies declined to undetectable levels by 45-60 days, but gastric ATPase autoantibodies declined more slowly requiring >100 days until undetectable. Further testing of IgG and/or IgA antibodies against a subset of potential targets identified by published autoantigen array studies of MIS-C failed to detect autoantibodies against most (16/18) of these proteins in patients with MIS-C who had not received IVIG. However, Troponin C2 and KLHL12 autoantibodies were detected in 2 of 20 and 1 of 20 patients with MIS-C, respectively. Overall, these results suggest that IVIG therapy may be a confounding factor in autoantibody measurements in MIS-C and that antibodies against antigens associated with autoimmune diseases or other human proteins are uncommon in MIS-C.Publication Deep immunophenotyping reveals biomarkers of multisystemic inflammatory syndrome in children in a Latin American cohort(2022) Rey, Emma; Espinosa, Yazmin; Astudillo, Camila; Jimena, Lina; Hormazábal, Juan; Noguera, Loreani; Cofré, Fernanda; Piñera, Cecilia; González, Ricardo; Bataszew, Alexander; Muñoz, Paula; Benadof, Dona; Álvarez, Patricia; Acevedo, Valeria; Vial, Pablo; Vial, Cecilia; Poli, CeciliaBackground: Multisystemic inflammatory syndrome in children (MIS-C) is a life-threatening disease that occurs 2-5 weeks after severe acute respiratory syndrome coronavirus 2 exposure and is characterized by severe multisystemic inflammation. Early recognition of MIS-C is key to prognosis; therefore, establishing clinical and laboratory biomarkers that predict complications is urgently needed. Objective: We characterized the immune response and clinical features of patients with acute MIS-C and determined biomarkers of disease in a cohort of 42 Latin American patients. Methods: Immune characterization was performed using flow cytometry from peripheral mononuclear cells and severe acute respiratory syndrome coronavirus 2-specific humoral and cellular response was performed using flow cytometry, enzyme-linked immunospot, enzyme-linked immunosorbent assay, and neutralizing antibody assays. Results: MIS-C is characterized by robust T-cell activation and cytokine storm. We uncovered that while C-X-C motif chemokine ligand (CXCL) 9, IL-10, CXCL8, CXCL10, IL-6, and IL-18 are significantly elevated in patients with shock, while CCL5 was increased in milder disease. Monocyte dysregulation was specifically associated with KD-like MIS-C. Interestingly, MIS-C patients show a natural killer cell degranulation defect that is persistent after 6 months of disease presentation, suggesting it could underlie disease susceptibility. Most MIS-C had gastrointestinal involvement, and higher levels of neopterin were identified in their stools, potentially representing a biomarker of intestinal inflammation in MIS-C. Severe acute respiratory syndrome coronavirus 2-specific cellular response and neutralizing antibodies were identifiable in convalescent MIS-C patients, suggesting sustained immunity. Conclusion: Clinical characterization and comprehensive immunophenotyping of Chilean MIS-C cohort provide valuable insights in understanding immune dysregulation in MIS-C and identify relevant biomarkers of disease that could be used to predict severity and organ involvement.Publication Multicenter analysis of neutrophil extracellular trap dysregulation in adult and pediatric COVID-19(2022) Carmona, Carmelo; Zhang, Yu; Dobbs, Kerry; Markowitz, Tovah; Dalgard, Clifton; Oler, Andrew; Claybaugh, Dillon; Draper, Deborah; Truong, Meng; Delmonte, Ottavia; Licciardi, Francesco; Ramenghi, Ugo; Crescenzio, Nicoletta; Imberti, Luisa; Sottini, Alessandra; Quaresima, Virginia; Fiorini, Chiara; Discepolo, Valentina; Lo Vecchio, Andrea; Guarino, Alfredo; Pierri, Luca; Catzola, Andrea; Biondi, Andrea; Bonfanti, Paolo; Poli, Cecilia; Espinosa, Yasmin; Astudillo, Camila; Rey, Emma; Vial, Cecilia; De la Cruz, Javiera; González, Ricardo; Pinera, Cecilia; Mays, Jacqueline; Ng, Ashley; Platt, Andrew; NIH COVID Autopsy Consortium; COVID STORM Clinicians; Drolet, Beth; Moon, John; Cowen, Edward; Kenney, Heather; Weber, Sarah; Castagnoli, Riccardo; Magliocco, Mary; Stack, Michael; Montealegre, Gina; Barron, Karyl; Fink, Danielle; Kuhns, Douglas; Hewitt, Stephen; Arkin, Lisa; Chertow, Daniel; Su, Helen; Notarangelo, Luigi; Kaplan, MarianaDysregulation in neutrophil extracellular trap (NET) formation and degradation may play a role in the pathogenesis and severity of COVID-19; however, its role in the pediatric manifestations of this disease, including multisystem inflammatory syndrome in children (MIS-C) and chilblain-like lesions (CLLs), otherwise known as "COVID toes," remains unclear. Studying multinational cohorts, we found that, in CLLs, NETs were significantly increased in serum and skin. There was geographic variability in the prevalence of increased NETs in MIS-C, in association with disease severity. MIS-C and CLL serum samples displayed decreased NET degradation ability, in association with C1q and G-actin or anti-NET antibodies, respectively, but not with genetic variants of DNases. In adult COVID-19, persistent elevations in NETs after disease diagnosis were detected but did not occur in asymptomatic infection. COVID-19-affected adults displayed significant prevalence of impaired NET degradation, in association with anti-DNase1L3, G-actin, and specific disease manifestations, but not with genetic variants of DNases. NETs were detected in many organs of adult patients who died from COVID-19 complications. Infection with the Omicron variant was associated with decreased NET levels when compared with other SARS-CoV-2 strains. These data support a role for NETs in the pathogenesis and severity of COVID-19 in pediatric and adult patients.Publication Partial loss-of-function mutations in GINS4 lead to NK cell deficiency with neutropenia(2022) Conte, Matilde; Poli, Cecilia; Taglialatela, Angelo; Leuzzi, Giuseppe; Chinn, Ivan; Salinas, Sandra; Rey, Emma; Olivares, Nixa; Veramendi, Liz; Ciccia, Alberto; Lupsk, James; Orange, Jordan; Aldave, Juan; Mace, Emily