B cell depletion therapies in autoimmune disease: advances and mechanistic insights

Lee, Dennis S. W.; Rojas, Olga L.; Gommerman, Jennifer L.

doi:10.1038/s41573-020-00092-2

Cited by 364 publications

(324 citation statements)

References 311 publications

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“…5b). These results suggest that antiviral antibodies were not lost during rituximab treatment as initially hypothesized, and furthermore that the source of S1-speci c IgG during the reinfection was likely due to long-lived plasma cells (which are not depleted by rituximab 35 ) generated during initial SARS-CoV-2 infection rather than a de novo response to the reinfection.…”

Section: Immunologic Pro Ling Reveals Naive Lymphocyte Depletion and Poor Humoral Immunitysupporting

confidence: 51%

Longitudinal immune profiling of a SARS-CoV-2 reinfection in a solid organ transplant recipient

Klein

Trubin²,

Lu³

et al. 2021

Preprint

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The underlying immunologic deficiencies enabling SARS-CoV-2 reinfections are currently unknown. Here we describe a renal-transplant recipient who developed recurrent, symptomatic SARS-CoV-2 infection 7 months after primary infection. To elucidate the immunological mechanisms responsible for reinfection, we performed longitudinal profiling of cellular and humoral responses during both primary and recurrent SARS-CoV-2 infection. We found that the patient responded to the primary infection with transient, poor-quality adaptive immune responses that was further compromised by intervening treatment for acute rejection of the renal allograft prior to reinfection. Importantly, we identified the development of neutralizing antibodies and humoral memory responses prior to SARS-CoV-2 reinfection. However, these neutralizing antibodies failed to confer protection against reinfection, suggesting that additional factors are required for efficient prevention of SARS-CoV-2 reinfection. Further, we found no evidence supporting viral evasion of primary adaptive immune responses, suggesting that susceptibility to reinfection may be determined by host factors rather than pathogen adaptation.

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Section: Immunologic Pro Ling Reveals Naive Lymphocyte Depletion and Poor Humoral Immunitysupporting

confidence: 51%

Longitudinal immune profiling of a SARS-CoV-2 reinfection in a solid organ transplant recipient

Klein

Trubin²,

Lu³

et al. 2021

Preprint

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“…Increasing evidence points to the critical role of autoimmunity in MS development and progression (144, 147), with many studies focusing on the contribution of T and B cells (144, 147, 148). In fact, therapies targeting T and B cells have demonstrated clinical success in the treatment of MS; these are reviewed in detail elsewhere (149)(150)(151).…”

Section: Nk Cells and Multiple Sclerosismentioning

confidence: 99%

NK Cells in Autoimmune Diseases: Protective or Pathogenic?

2021

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Autoimmune diseases generally result from the loss of self-tolerance (i.e., failure of the immune system to distinguish self from non-self), and are characterized by autoantibody production and hyperactivation of T cells, which leads to damage of specific or multiple organs. Thus, autoimmune diseases can be classified as organ-specific or systemic. Genetic and environmental factors contribute to the development of autoimmunity. Recent studies have demonstrated the contribution of innate immunity to the onset of autoimmune diseases. Natural killer (NK) cells, which are key components of the innate immune system, have been implicated in the development of multiple autoimmune diseases such as systemic lupus erythematosus, type I diabetes mellitus, and autoimmune liver disease. However, NK cells have both protective and pathogenic roles in autoimmunity depending on the NK cell subset, microenvironment, and disease type or stage. In this work, we review the current knowledge of the varied roles of NK cell subsets in systemic and organic-specific autoimmune diseases and their clinical potential as therapeutic targets.

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“…Anti-CD20 antibody (aCD20) based B cell depleting strategies are implemented in hematologic malignancies 13 and across a variety of autoimmune disorders 14 , including MS 15,16 , with high rates of success. Upon antigen exposure, B cells have the ability to form memory cells or differentiate into plasmablasts and plasma cells 17 .…”

Section: Introductionmentioning

confidence: 99%

Altered cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy

Apostolidis

Kakara

Painter

et al. 2021

Preprint

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SARS-CoV-2 mRNA vaccination in healthy individuals generates effective immune protection against COVID-19. Little is known, however, about the SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed patients. We investigated induction of antigen-specific antibody, B cell and T cell responses in patients with multiple sclerosis on anti-CD20 (MS-aCD20) monotherapy following SARS-CoV-2 mRNA vaccination. Treatment with aCD20 significantly reduced Spike and RBD specific antibody and memory B cell responses in most patients, an effect that was ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. In contrast, all MS-aCD20 patients generated antigen-specific CD4 and CD8 T-cell responses following vaccination. However, treatment with aCD20 skewed these responses compromising circulating Tfh responses and augmenting CD8 T cell induction, while largely preserving Th1 priming. These data also revealed underlying features of coordinated immune responses following mRNA vaccination. Specifically, the MS-aCD20 patients who failed to generate anti-RBD IgG had the most severe defect in cTfh cell responses and more robust CD8 T cell responses compared to those who generated anti-RBD IgG, whose T cell responses were more similar to healthy controls. These data define the nature of SARS-CoV-2 vaccine-induced immune landscape in aCD20-treated patients, and provide insights into coordinated mRNA vaccine-induced immune responses in humans. Our findings have implications for clinical decision-making, patient education and public health policy for patients treated with aCD20 and other immunosuppressed patients.

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B cell depletion therapies in autoimmune disease: advances and mechanistic insights

Cited by 364 publications

References 311 publications

Longitudinal immune profiling of a SARS-CoV-2 reinfection in a solid organ transplant recipient

Longitudinal immune profiling of a SARS-CoV-2 reinfection in a solid organ transplant recipient

NK Cells in Autoimmune Diseases: Protective or Pathogenic?

Altered cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy

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