tetano
Editor, Senior Moderator
Cell Death Dis
. 2022 Aug 27;13(8):741.
doi: 10.1038/s41419-022-05190-0.
Low quantity and quality of anti-spike humoral response is linked to CD4 T-cell apoptosis in COVID-19 patients
Sonia André[SUP] #[/SUP][SUP] 1 [/SUP], Marne Azarias da Silva[SUP] #[/SUP][SUP] 1 [/SUP], Morgane Picard[SUP] 1 [/SUP], Aurélie Alleaume-Buteau[SUP] 1 2 [/SUP], Lucy Kundura[SUP] 3 [/SUP], Renaud Cezar[SUP] 3 [/SUP], Calaiselvy Soudaramourty[SUP] 1 [/SUP], Santa Cruz André[SUP] 4 5 6 7 [/SUP], Ana Mendes-Frias[SUP] 6 7 [/SUP], Alexandre Carvalho[SUP] 4 5 6 7 [/SUP], Carlos Capela[SUP] 4 5 6 7 [/SUP], Jorge Pedrosa[SUP] 4 5 [/SUP], António Gil Castro[SUP] 4 5 [/SUP], Paul Loubet[SUP] 8 [/SUP], Albert Sotto[SUP] 8 [/SUP], Laurent Muller[SUP] 9 [/SUP], Jean-Yves Lefrant[SUP] 9 [/SUP], Claire Roger[SUP] 9 [/SUP], Pierre-Géraud Claret[SUP] 10 [/SUP], Sandra Duvnjak[SUP] 11 [/SUP], Tu-Anh Tran[SUP] 12 [/SUP], Ouafa Zghidi-Abouzid[SUP] 13 [/SUP], Pierre Nioche[SUP] 1 2 [/SUP], Ricardo Silvestre[SUP] #[/SUP][SUP] 4 5 [/SUP], Pierre Corbeau[SUP] #[/SUP][SUP] 14 15 [/SUP], Fabrizio Mammano[SUP] #[/SUP][SUP] 16 17 [/SUP], Jérôme Estaquier[SUP] #[/SUP][SUP] 18 19 [/SUP]
Affiliations
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.
. 2022 Aug 27;13(8):741.
doi: 10.1038/s41419-022-05190-0.
Low quantity and quality of anti-spike humoral response is linked to CD4 T-cell apoptosis in COVID-19 patients
Sonia André[SUP] #[/SUP][SUP] 1 [/SUP], Marne Azarias da Silva[SUP] #[/SUP][SUP] 1 [/SUP], Morgane Picard[SUP] 1 [/SUP], Aurélie Alleaume-Buteau[SUP] 1 2 [/SUP], Lucy Kundura[SUP] 3 [/SUP], Renaud Cezar[SUP] 3 [/SUP], Calaiselvy Soudaramourty[SUP] 1 [/SUP], Santa Cruz André[SUP] 4 5 6 7 [/SUP], Ana Mendes-Frias[SUP] 6 7 [/SUP], Alexandre Carvalho[SUP] 4 5 6 7 [/SUP], Carlos Capela[SUP] 4 5 6 7 [/SUP], Jorge Pedrosa[SUP] 4 5 [/SUP], António Gil Castro[SUP] 4 5 [/SUP], Paul Loubet[SUP] 8 [/SUP], Albert Sotto[SUP] 8 [/SUP], Laurent Muller[SUP] 9 [/SUP], Jean-Yves Lefrant[SUP] 9 [/SUP], Claire Roger[SUP] 9 [/SUP], Pierre-Géraud Claret[SUP] 10 [/SUP], Sandra Duvnjak[SUP] 11 [/SUP], Tu-Anh Tran[SUP] 12 [/SUP], Ouafa Zghidi-Abouzid[SUP] 13 [/SUP], Pierre Nioche[SUP] 1 2 [/SUP], Ricardo Silvestre[SUP] #[/SUP][SUP] 4 5 [/SUP], Pierre Corbeau[SUP] #[/SUP][SUP] 14 15 [/SUP], Fabrizio Mammano[SUP] #[/SUP][SUP] 16 17 [/SUP], Jérôme Estaquier[SUP] #[/SUP][SUP] 18 19 [/SUP]
Affiliations
- PMID: 36030261
- DOI: 10.1038/s41419-022-05190-0
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.