scholarly journals Discrepant Antigen-specific Antibody Responses Causing SARS-CoV-2 Persistence in a Patient Receiving B-cell-targeted Therapy with Rituximab

2021 ◽  
Vol 60 (23) ◽  
pp. 3827-3831
Author(s):  
Teruhito Takakuwa ◽  
Yu Nakagama ◽  
Mayo Yasugi ◽  
Toshiki Maeda ◽  
Kenji Matsuo ◽  
...  
2014 ◽  
Vol 209 (9) ◽  
pp. 1354-1361 ◽  
Author(s):  
Kuan-Ying Arthur Huang ◽  
Chris Ka-Fai Li ◽  
Elizabeth Clutterbuck ◽  
Cecilia Chui ◽  
Tom Wilkinson ◽  
...  

Author(s):  
Renata Varnaitė ◽  
Marina García ◽  
Hedvig Glans ◽  
Kimia T. Maleki ◽  
John Tyler Sandberg ◽  
...  

AbstractCoronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 and has since become a global pandemic. Pathogen-specific antibodies are typically a major predictor of protective immunity, yet B cell and antibody responses during COVID-19 are not fully understood. Here, we analyzed antibody-secreting cell (ASC) and antibody responses in twenty hospitalized COVID-19 patients. The patients exhibited typical symptoms of COVID-19, and presented with reduced lymphocyte numbers and increased T cell and B cell activation. Importantly, we detected an expansion of SARS-CoV-2 nucleocapsid protein-specific ASCs in all twenty COVID-19 patients using a multicolor FluoroSpot assay. Out of the 20 patients, 16 had developed SARS-CoV-2-neutralizing antibodies by the time of inclusion in the study. SARS-CoV-2-specific IgA, IgG and IgM antibody levels positively correlated with SARS-CoV-2-neutralizing antibody titers, suggesting that SARS-CoV-2-specific antibody levels may reflect the titers of neutralizing antibodies in COVID-19 patients during the acute phase of infection. Lastly, we showed that interleukin 6 (IL-6) and C-reactive protein (CRP) concentrations were higher in serum of patients who were hospitalized for longer, supporting the recent observations that IL-6 and CRP could be used to predict COVID-19 severity. Altogether, this study constitutes a detailed description of clinical and immunological parameters in twenty COVID-19 patients, with a focus on B cell and antibody responses, and provides tools to study immune responses to SARS-CoV-2 infection and vaccination.


Vaccine ◽  
2011 ◽  
Vol 29 (49) ◽  
pp. 9132-9136 ◽  
Author(s):  
Hemangi B. Shah ◽  
Sunil K. Joshi ◽  
Mark L. Lang

2018 ◽  
Vol 115 (8) ◽  
pp. 1901-1906 ◽  
Author(s):  
Fleur S. van de Bovenkamp ◽  
Ninotska I. L. Derksen ◽  
Pleuni Ooijevaar-de Heer ◽  
Karin A. van Schie ◽  
Simone Kruithof ◽  
...  

A hallmark of B-cell immunity is the generation of a diverse repertoire of antibodies from a limited set of germline V(D)J genes. This repertoire is usually defined in terms of amino acid composition. However, variable domains may also acquire N-linked glycans, a process conditional on the introduction of consensus amino acid motifs (N-glycosylation sites) during somatic hypermutation. High levels of variable domain glycans have been associated with autoantibodies in rheumatoid arthritis, as well as certain follicular lymphomas. However, the role of these glycans in the humoral immune response remains poorly understood. Interestingly, studies have reported both positive and negative effects on antibody affinity. Our aim was to elucidate the role of variable domain glycans during antigen-specific antibody responses. By analyzing B-cell repertoires by next-generation sequencing, we demonstrate that N-glycosylation sites are introduced at positions in which glycans can affect antigen binding as a result of a specific clustering of progenitor glycosylation sites in the germline sequences of variable domain genes. By analyzing multiple human monoclonal and polyclonal (auto)antibody responses, we subsequently show that this process is subject to selection during antigen-specific antibody responses, skewed toward IgG4, and positively contributes to antigen binding. Together, these results highlight a physiological role for variable domain glycosylation as an additional layer of antibody diversification that modulates antigen binding.


2016 ◽  
Vol 137 (1) ◽  
pp. 157-167 ◽  
Author(s):  
Ramona A. Hoh ◽  
Shilpa A. Joshi ◽  
Yi Liu ◽  
Chen Wang ◽  
Krishna M. Roskin ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document