Low quantity and quality of anti-spike humoral response is linked to CD4 T-cell apoptosis in COVID-19 patients - Archive ouverte HAL Access content directly
Journal Articles Cell Death and Disease Year : 2022

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

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Jean-Yves Lefrant

Abstract

Abstract 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.
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Dates and versions

inserm-03774218 , version 1 (09-09-2022)

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Cite

Sonia André, Marne Azarias da Silva, Morgane Picard, Aurélie Alleaume-Buteau, Lucy Kundura, et al.. Low quantity and quality of anti-spike humoral response is linked to CD4 T-cell apoptosis in COVID-19 patients. Cell Death and Disease, 2022, 13 (8), pp.741. ⟨10.1038/s41419-022-05190-0⟩. ⟨inserm-03774218⟩
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