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Low quantity and quality of anti-spike humoral response is linked to CD4 T-cell apoptosis in COVID-19 patients

In addition to an inflammatory reaction, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-infected patients present lymphopenia, which we recently reported as being related to abnormal programmed cell death. As an efficient humoral response requires CD4 T-cell help, we hypothesized that...

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Detalles Bibliográficos
Autores principales: André, Sonia, Azarias da Silva, Marne, Picard, Morgane, Alleaume-Buteau, Aurélie, Kundura, Lucy, Cezar, Renaud, Soudaramourty, Calaiselvy, André, Santa Cruz, Mendes-Frias, Ana, Carvalho, Alexandre, Capela, Carlos, Pedrosa, Jorge, Gil Castro, António, Loubet, Paul, Sotto, Albert, Muller, Laurent, Lefrant, Jean-Yves, Roger, Claire, Claret, Pierre-Géraud, Duvnjak, Sandra, Tran, Tu-Anh, Zghidi-Abouzid, Ouafa, Nioche, Pierre, Silvestre, Ricardo, Corbeau, Pierre, Mammano, Fabrizio, Estaquier, Jérôme
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9419645/
https://www.ncbi.nlm.nih.gov/pubmed/36030261
http://dx.doi.org/10.1038/s41419-022-05190-0
Descripción
Sumario:In addition to an inflammatory reaction, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-infected patients present lymphopenia, which we recently reported as being related to abnormal programmed cell death. As an efficient humoral response requires CD4 T-cell help, we hypothesized that the propensity of CD4 T cells to die may impact the quantity and quality of the humoral response in acutely infected individuals. In addition to specific immunoglobulins (Ig)A, IgM, and IgG against SARS-CoV-2 nucleocapsid (N), membrane (M), and spike (S1) proteins, we assessed the quality of IgG response by measuring the avidity index. Because the S protein represents the main target for neutralization and antibody-dependent cellular cytotoxicity responses, we also analyzed anti-S-specific IgG using S-transfected cells (S-Flow). Our results demonstrated that most COVID-19 patients have a predominant IgA anti-N humoral response during the early phase of infection. This specific humoral response preceded the anti-S1 in time and magnitude. The avidity index of anti-S1 IgG was low in acutely infected individuals compared to convalescent patients. We showed that the percentage of apoptotic CD4 T cells is inversely correlated with the levels of specific IgG antibodies. These lower levels were also correlated positively with plasma levels of CXCL10, a marker of disease severity, and soluble Fas ligand that contributes to T-cell death. Finally, we found lower S-Flow responses in patients with higher CD4 T-cell apoptosis. Altogether, these results demonstrate that individuals with high levels of CD4 T-cell apoptosis and CXCL10 have a poor ability to build an efficient anti-S response. Consequently, preventing CD4 T-cell death might be a strategy for improving humoral response during the acute phase, thereby reducing COVID-19 pathogenicity.