Dampening of CD8+ T Cell Response by B Cell Depletion Therapy in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

Néel, A.; Bucchia, M.; Néel, Mélanie; Tilly, Gaëlle; Caristan, A.; Yap, Michele; Rimbert, Marie; Bruneau, Sarah; Cadoux, Mathilde; Agard, C.; Hourmant, Maryvonne; Godmer, Pascal; Brouard, Sophie; Bressollette, Céline; Hamidou, M.; Josien, Régis; Fakhouri, Fádi; Degauque, Nicolas

doi:10.1002/art.40766

Cited by 26 publications

(22 citation statements)

References 40 publications

(53 reference statements)

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“…This is additionally applicable to disease settings in which limiting the function of CD8 T cells by depleting B cells may be beneficial. Rituximab use in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) alters the CD8 T cell memory compartment, reducing the frequency of effector memory cells re-expressing CD45RA (TEMRA) ( Néel et al, 2019 ). B cells isolated from these patients increased the cytokine output of CD8 T cells in ex vivo co-cultures, providing evidence for a direct, positive effect of B cells on CD8 T cells in this disease setting, where CD8 T cells are pathogenic.…”

Section: Discussionmentioning

confidence: 99%

B cells promote CD8 T cell primary and memory responses to subunit vaccines

et al. 2021

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SUMMARY The relationship between B cells and CD4 T cells has been carefully studied, revealing a collaborative effort in which B cells promote the activation, differentiation, and expansion of CD4 T cells while the so-called “helper” cells provide signals to B cells, influencing their class switching and fate. Interactions between B cells and CD8 T cells are not as well studied, although CD8 T cells exhibit an accelerated contraction after certain infections in B-cell-deficient mice. Here, we find that B cells significantly enhance primary CD8 T cell responses after vaccination. Moreover, memory CD8 numbers and function are impaired in B-cell-deficient animals, leading to increased susceptibility to bacterial challenge. We also show that interleukin-27 production by B cells contributes to their impact on primary, but not memory, CD8 responses. Better understanding of the interactions between CD8 T cells and B cells may aid in the design of more effective future vaccine strategies.

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Section: Discussionmentioning

confidence: 99%

B cells promote CD8 T cell primary and memory responses to subunit vaccines

et al. 2021

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“…As an example, one study in AAV found that whereas rituximab treatment did not affect CD4+ and Treg frequencies, it was associated with reduced CD8+ T EMRA frequencies and circulating chemokine and cytokine levels. Interestingly, co-cultures of CD8+ T cells and autologous B cells from AAV patients resulted in enhanced production of proinflammatory cytokines indicating a pathogenic crosstalk between B cells and CD8+ T cells ( 117 ).…”

Section: Discussionmentioning

confidence: 99%

CD8+ T Cells in GCA and GPA: Bystanders or Active Contributors?

et al. 2021

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Vasculitis refers to inflammation of blood vessels and can cause a variety of serious complications depending on which vessels are affected. Two different forms of vasculitis are Giant Cell Arteritis (GCA) and Granulomatosis with Polyangiitis (GPA). GCA is the most common form of vasculitis in adults affecting the large arteries and can lead to visual impairment and development of aneurysms. GPA affects small- and medium-sized blood vessels predominantly in the lungs and kidneys resulting in organ failure. Both diseases can potentially be fatal. Although the pathogenesis of GCA and GPA are incompletely understood, a prominent role for CD4+ T cells has been implicated in both diseases. More recently, the role of CD8+ T cells has gained renewed interest. CD8+ T cells are important players in the adaptive immune response against intracellular microorganisms. After a general introduction on the different forms of vasculitis and their association with infections and CD8+ T cells, we review the current knowledge on CD8+ T-cell involvement in the immunopathogenesis of GCA and GPA focusing on phenotypic and functional features of circulating and lesional CD8+ T cells. Furthermore, we discuss to which extent aging is associated with CD8+ T-cell phenotype and function in GCA and GPA.

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“… 8 6) As opposed to depleting T cells with cyclophosphamide, rituximab can disrupt the pathogenic B cell/CD8+ T cell axis, leading to a reduction in T cell cytokine production and subsequently less renal endothelial damage without hindering CPI antitumor activity. 39 40 In addition, the malignancy risk was reported to be lower in rituximab-treated ANCA-associated vasculitis patients than in cyclophosphamide-treated patients. 41 42 …”

Section: Discussionmentioning

confidence: 99%

Checkpoint inhibitor-related renal vasculitis and use of rituximab

Mamlouk

Lin

Abdelrahim

et al. 2020

J Immunother Cancer

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The percentage of patients with cancer eligible for checkpoint inhibitor (CPI) therapy has increased rapidly over the past few years and approaches 45%. As a result, more cases of CPI-related nephrotoxicity, including a rare subset with vasculitis, are being reported. To elucidate the clinical presentation of CPI-associated renal vasculitis and its possible mechanisms, treatment options and prognosis, we describe cases from a comprehensive cancer center and reviewed the literature for similar cases. We retrospectively reviewed the charts of all patients with cancer from 2014 to 2020 who were diagnosed with CPI-related nephrotoxicity and underwent a kidney biopsy. We identified five cases of renal vasculitis: three patients were diagnosed with seronegative antineutrophil cytoplasm antibody (ANCA)-associated vasculitis, one case with seropositive ANCA-associated vasculitis and one case was diagnosed with IgA vasculitis. Of these cases, four patients were receiving nivolumab, and one patient was receiving tremelimumab. All patients had microscopic hematuria, four out of five patients had negative ANCA serology, one patient had concurrent lung involvement and positive ANCA serology, and all had severe acute kidney injury with creatinine >4.50 mg/dL on diagnosis. All patients were treated by discontinuing CPI and initiating corticosteroids and rituximab. Three patients received plasmapheresis; two of these required renal replacement therapy including the patient with lung involvement. All patients after rituximab had a partial or complete renal response. Two patients died within 8 months of diagnosis due to malignancy progression. None of the patients had a relapse of vasculitis. We demonstrated that CPI can be associated with different types of renal vasculitis that are predominantly ANCA negative and manifest as severe acute kidney injury. Despite the lack of strong evidence, treatment similar to treatment of primary seropositive ANCA-associated vasculitis with corticosteroids and rituximab is well tolerated with favorable renal outcomes.

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Dampening of CD8+ T Cell Response by B Cell Depletion Therapy in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

Cited by 26 publications

References 40 publications

B cells promote CD8 T cell primary and memory responses to subunit vaccines

B cells promote CD8 T cell primary and memory responses to subunit vaccines

CD8+ T Cells in GCA and GPA: Bystanders or Active Contributors?

Checkpoint inhibitor-related renal vasculitis and use of rituximab

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