Low quantity and quality of anti-spike humoral response is linked to CD4 T-cell apoptosis in COVID-19 patients
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 hypothesi...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-08-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-05190-0 |
| _version_ | 1811183281283006464 |
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| author | Sonia André Marne Azarias da Silva Morgane Picard Aurélie Alleaume-Buteau Lucy Kundura Renaud Cezar Calaiselvy Soudaramourty Santa Cruz André Ana Mendes-Frias Alexandre Carvalho Carlos Capela Jorge Pedrosa António Gil Castro Paul Loubet Albert Sotto Laurent Muller Jean-Yves Lefrant Claire Roger Pierre-Géraud Claret Sandra Duvnjak Tu-Anh Tran Ouafa Zghidi-Abouzid Pierre Nioche Ricardo Silvestre Pierre Corbeau Fabrizio Mammano Jérôme Estaquier |
| author_facet | Sonia André Marne Azarias da Silva Morgane Picard Aurélie Alleaume-Buteau Lucy Kundura Renaud Cezar Calaiselvy Soudaramourty Santa Cruz André Ana Mendes-Frias Alexandre Carvalho Carlos Capela Jorge Pedrosa António Gil Castro Paul Loubet Albert Sotto Laurent Muller Jean-Yves Lefrant Claire Roger Pierre-Géraud Claret Sandra Duvnjak Tu-Anh Tran Ouafa Zghidi-Abouzid Pierre Nioche Ricardo Silvestre Pierre Corbeau Fabrizio Mammano Jérôme Estaquier |
| author_sort | Sonia André |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T09:45:26Z |
| format | Article |
| id | doaj.art-6fecc8e6b5164568af51fbebea43c83e |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-11T09:45:26Z |
| publishDate | 2022-08-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-6fecc8e6b5164568af51fbebea43c83e2022-12-22T04:31:05ZengNature Publishing GroupCell Death and Disease2041-48892022-08-0113811510.1038/s41419-022-05190-0Low quantity and quality of anti-spike humoral response is linked to CD4 T-cell apoptosis in COVID-19 patientsSonia André0Marne Azarias da Silva1Morgane Picard2Aurélie Alleaume-Buteau3Lucy Kundura4Renaud Cezar5Calaiselvy Soudaramourty6Santa Cruz André7Ana Mendes-Frias8Alexandre Carvalho9Carlos Capela10Jorge Pedrosa11António Gil Castro12Paul Loubet13Albert Sotto14Laurent Muller15Jean-Yves Lefrant16Claire Roger17Pierre-Géraud Claret18Sandra Duvnjak19Tu-Anh Tran20Ouafa Zghidi-Abouzid21Pierre Nioche22Ricardo Silvestre23Pierre Corbeau24Fabrizio Mammano25Jérôme Estaquier26Université Paris Cité, INSERM U1124Université Paris Cité, INSERM U1124Université Paris Cité, INSERM U1124Université Paris Cité, INSERM U1124Laboratoire d’Immunologie, CHU de NîmesLaboratoire d’Immunologie, CHU de NîmesUniversité Paris Cité, INSERM U1124Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of MinhoDepartment of Internal Medicine, Hospital of BragaLife and Health Sciences Research Institute (ICVS), School of Health Sciences, University of MinhoLife and Health Sciences Research Institute (ICVS), School of Health Sciences, University of MinhoLife and Health Sciences Research Institute (ICVS), School of Health Sciences, University of MinhoLife and Health Sciences Research Institute (ICVS), School of Health Sciences, University of MinhoService des Maladies Infectieuses et Tropicales, CHU de NîmesService des Maladies Infectieuses et Tropicales, CHU de NîmesService de Réanimation Chirugicale, CHU de NîmesService de Réanimation Chirugicale, CHU de NîmesService de Réanimation Chirugicale, CHU de NîmesUrgences Médico-Chirugicales Hospitalisation, CHU de NîmesService de Gérontologie et Prévention du Vieillissement, CHU de NîmesService de Pédiatrie, CHU de NîmesCHU de Québec—Université Laval Research CenterUniversité Paris Cité, INSERM U1124Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of MinhoLaboratoire d’Immunologie, CHU de NîmesUniversité Paris Cité, INSERM U1124Université Paris Cité, INSERM U1124Abstract 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.https://doi.org/10.1038/s41419-022-05190-0 |
| spellingShingle | Sonia André Marne Azarias da Silva Morgane Picard Aurélie Alleaume-Buteau Lucy Kundura Renaud Cezar Calaiselvy Soudaramourty Santa Cruz André Ana Mendes-Frias Alexandre Carvalho Carlos Capela Jorge Pedrosa António Gil Castro Paul Loubet Albert Sotto Laurent Muller Jean-Yves Lefrant Claire Roger Pierre-Géraud Claret Sandra Duvnjak Tu-Anh Tran Ouafa Zghidi-Abouzid Pierre Nioche Ricardo Silvestre Pierre Corbeau Fabrizio Mammano Jérôme Estaquier Low quantity and quality of anti-spike humoral response is linked to CD4 T-cell apoptosis in COVID-19 patients Cell Death and Disease |
| title | Low quantity and quality of anti-spike humoral response is linked to CD4 T-cell apoptosis in COVID-19 patients |
| title_full | Low quantity and quality of anti-spike humoral response is linked to CD4 T-cell apoptosis in COVID-19 patients |
| title_fullStr | Low quantity and quality of anti-spike humoral response is linked to CD4 T-cell apoptosis in COVID-19 patients |
| title_full_unstemmed | Low quantity and quality of anti-spike humoral response is linked to CD4 T-cell apoptosis in COVID-19 patients |
| title_short | Low quantity and quality of anti-spike humoral response is linked to CD4 T-cell apoptosis in COVID-19 patients |
| title_sort | low quantity and quality of anti spike humoral response is linked to cd4 t cell apoptosis in covid 19 patients |
| url | https://doi.org/10.1038/s41419-022-05190-0 |
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