Antibody-dependent enhancement (ADE) of SARS-CoV-2 in patients exposed to MERS-CoV and SARS-CoV-2 antigens.

This study evaluated the potential for antibody-dependent enhancement (ADE) in serum samples from patients exposed to Middle East respiratory syndrome coronavirus (MERS-CoV). Furthermore, we evaluated the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination on ADE in individuals with a MERS infection history. We performed ADE assay in sera from MERS recovered and SARS-CoV-2-vaccinated individuals using BHK cells expressing FcgRIIa, SARS-CoV-2, and MERS-CoV pseudoviruses (PVs). Further, we analyzed the association of ADE to serum IgG levels and neutralization. Out of 16 MERS patients, nine demonstrated ADE against SARS-CoV-2 PV, however, none of the samples demonstrated ADE against MERS-CoV PV. Furthermore, out of the seven patients exposed to SARS-CoV-2 vaccination after MERS-CoV infection, only one patient (acutely infected with MERS-CoV) showed ADE for SARS-CoV-2 PV. Further analysis indicated that IgG1, IgG2, and IgG3 against SARS-CoV-2 S1 and RBD subunits, IgG1 and IgG2 against the MERS-CoV S1 subunit, and serum neutralizing activity were low in ADE-positive samples. In summary, samples from MERS-CoV-infected patients exhibited ADE against SARS-CoV-2 and was significantly associated with low levels of neutralizing antibodies. Subsequent exposure to SARS-CoV-2 vaccination resulted in diminished ADE activity while the PV neutralization assay demonstrated a broadly reactive antibody response in some patient samples.

Inhibitory affinity modulation of FcγRIIA ligand binding by glycosphingolipids by inside-out signaling.

The interaction of the human FcγRIIA with immune complexes (ICs) promotes neutrophil activation and thus must be tightly controlled to avoid damage to healthy tissue. Here, we demonstrate that a fungal-derived soluble ß-1,3/1,6-glucan binds to the glycosphingolipid long-chain lactosylceramide (LacCer) to reduce FcγRIIA-mediated recruitment to immobilized ICs under flow, a process requiring high-affinity FcγRIIA-immunoglobulin G (IgG) interactions. The inhibition requires Lyn phosphorylation of SHP-1 phosphatase and the FcγRIIA immunotyrosine-activating motif. ß-glucan reduces the effective 2D affinity of FcγRIIA for IgG via Lyn and SHP-1 and, in vivo, inhibits FcγRIIA-mediated neutrophil recruitment to intravascular IgG deposited in the kidney glomeruli in a glycosphingolipid- and Lyn-dependent manner. In contrast, ß-glucan did not affect FcγR functions that bypass FcγR affinity for IgG. In summary, we have identified a pathway for modulating the 2D affinity of FcγRIIA for ligand that relies on LacCer-Lyn-SHP-1-mediated inhibitory signaling triggered by ß-glucan, a previously described activator of innate immunity.

Nuevas evidencias en la susceptibilidad a la infección por dengue asociadas al polimorfismo HH del receptor FcgRIIa / New evidence in the susceptibility to dengue infection associated to HH polymorphism of FcgRlla receptor

Introducción: las variantes polimórficas del receptor FcgR IIa han sido asociadas con la susceptibilidad a padecer diferentes enfermedades infecciosas. Recientemente se reportó la asociación entre el polimorfismo de este receptor y la susceptibilidad a padecer la fiebre hemorrágica por dengue. Objetivos: explorar si la asociación a la susceptibilidad o protección de las variantes homocigóticas del receptor, pudieran estar relacionadas además, con los títulos de IgG y la exposición a diferente número de infecciones. Métodos: se hizo un estudio de tipo analítico retrospectivo a individuos infectados por virus dengue 4 en Ciudad de La Habana durante la epidemia de 2006, que se contactaron en 2008. Se reclutó un total de 97 individuos, de los cuales 68 habían padecido fiebre dengue y 29 fiebre hemorrágica de dengue.Se les extrajo una muestra de 10 mL de sangre total en anticoagulante que se empleó en el aislamiento de ADN. Se determinó el polimorfismo genético del receptor FcgRIIa, los títulos de anticuerpos totales IgG anti-dengue y el antecedente de infección por dengue. Resultados: se evidenció, de modo interesante, una relación directamente proporcional y muy significativa (p< 0,0001) entre los altos títulos de IgG anti-dengue con el número de infecciones padecidas. Este comportamiento fue característico en los individuos con la variante homocigótica HH. Conclusiones: al parecer, en aquellos individuos con polimorfismo para el receptor FcgRIIa-H/H podría haber una tendencia a la no eliminación de los anticuerpos IgG a través del FcgRIIa, la cual está asociada con el número de infecciones(AU)

Introduction: polymorphic variants of FcgRIIa receptor have been associated to susceptibility to develop several infectious diseases. The relationship between the polymorphism of this receptor and the susceptibility to dengue hemorrhagic fever was recently reported. Objectives: to explore whether the association of the homocygotic variants of the receptor to susceptibility to or protection from a disease could be also related with the IgG antibody titters and the exposure to a number of infections. Methods: a retrospective analytical study was performed on individuals who had been infected with the dengue virus 4 during the 2006 epidemic in the City of Havana and were tracked down in 2008. A total number of 97 individuals were recruited of whom 68 had suffered dengue fever and 29 had had dengue hemorrhagic fever. A 10 mL blood sample was taken from each of them and then placed in EDTA anticoagulant for DNA isolation and 5ml placed in dry tubes to obtain serum. The genetic polymorphism of FcgRlla receptor, the total anti-dengue IgG antibody titers and the antecedent of dengue infection were determined. Results: it was interesting to note that there was very significant direct relation (p< 0.0001) between high anti-dengue IgG antibodies titers and the number of infections suffered by these people. This behaviour was present in those individuals with the HH homocygotic variant. Conclusion: it seems that those individuals with polymorphism in FCgRlla-H/H receptor would tend to non-elimination of IgG antibodies through this receptor, which is associated to the number of infections suffered by the individual(AU)

Nuevas evidencias en la susceptibilidad a la infección por dengue asociadas al polimorfismo HH del receptor FcgRIIa / New evidence in the susceptibility to dengue infection associated to HH polymorphism of FcgRlla receptor

Introducción: las variantes polimórficas del receptor FcgR IIa han sido asociadas con la susceptibilidad a padecer diferentes enfermedades infecciosas. Recientemente se reportó la asociación entre el polimorfismo de este receptor y la susceptibilidad a padecer la fiebre hemorrágica por dengue. Objetivos: explorar si la asociación a la susceptibilidad o protección de las variantes homocigóticas del receptor, pudieran estar relacionadas además, con los títulos de IgG y la exposición a diferente número de infecciones. Métodos: se hizo un estudio de tipo analítico retrospectivo a individuos infectados por virus dengue 4 en Ciudad de La Habana durante la epidemia de 2006, que se contactaron en 2008. Se reclutó un total de 97 individuos, de los cuales 68 habían padecido fiebre dengue y 29 fiebre hemorrágica de dengue.Se les extrajo una muestra de 10 mL de sangre total en anticoagulante que se empleó en el aislamiento de ADN. Se determinó el polimorfismo genético del receptor FcgRIIa, los títulos de anticuerpos totales IgG anti-dengue y el antecedente de infección por dengue. Resultados: se evidenció, de modo interesante, una relación directamente proporcional y muy significativa (p< 0,0001) entre los altos títulos de IgG anti-dengue con el número de infecciones padecidas. Este comportamiento fue característico en los individuos con la variante homocigótica HH. Conclusiones: al parecer, en aquellos individuos con polimorfismo para el receptor FcgRIIa-H/H podría haber una tendencia a la no eliminación de los anticuerpos IgG a través del FcgRIIa, la cual está asociada con el número de infecciones.

Introduction: polymorphic variants of FcgRIIa receptor have been associated to susceptibility to develop several infectious diseases. The relationship between the polymorphism of this receptor and the susceptibility to dengue hemorrhagic fever was recently reported. Objectives: to explore whether the association of the homocygotic variants of the receptor to susceptibility to or protection from a disease could be also related with the IgG antibody titters and the exposure to a number of infections. Methods: a retrospective analytical study was performed on individuals who had been infected with the dengue virus 4 during the 2006 epidemic in the City of Havana and were tracked down in 2008. A total number of 97 individuals were recruited of whom 68 had suffered dengue fever and 29 had had dengue hemorrhagic fever. A 10 mL blood sample was taken from each of them and then placed in EDTA anticoagulant for DNA isolation and 5ml placed in dry tubes to obtain serum. The genetic polymorphism of FcgRlla receptor, the total anti-dengue IgG antibody titers and the antecedent of dengue infection were determined. Results: it was interesting to note that there was very significant direct relation (p< 0.0001) between high anti-dengue IgG antibodies titers and the number of infections suffered by these people. This behaviour was present in those individuals with the HH homocygotic variant. Conclusion: it seems that those individuals with polymorphism in FCgRlla-H/H receptor would tend to non-elimination of IgG antibodies through this receptor, which is associated to the number of infections suffered by the individual.