Peribronchial tertiary lymphoid structures persist after rituximab therapy in patients with cystic fibrosis

Regard, Lucile; Martin, Clémence; Zemoura, L.; Geolier, Virginie; Sage, Édouard; Burgel, Pierre‐Régis

doi:10.1136/jclinpath-2018-205160

Cited by 5 publications

(4 citation statements)

References 9 publications

(14 reference statements)

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“…Following transplantation of rheumatoid arthritis synovial tissue or salivary glands from Sjögren's syndrome patients into mice with severe combined immunodeficiency (SCID), the tissue microenvironment supports the long term survival of ELS, maintains expression of AID and the secretion of autoantibodies (ACPA in rheumatoid arthritis; anti-Ro/SSA and anti-La/SSB in Sjögren's syndrome) [27,52]. Such persistence of ELS without contribution from the peripheral B cell pool is consistent with reports that ELS can survive B cell depletion therapy (Rituximab) [53][54][55][56]. Here, heightened expression of B cell activating factor (BAFF) at ELS provides a local survival signal for B cells.…”

Section: Els As Propogators Of Autoimmunity and Anti-tumour Immunitysupporting

confidence: 81%

Emerging roles for IL-6 family cytokines as positive and negative regulators of ectopic lymphoid structures

et al. 2021

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Section: Els As Propogators Of Autoimmunity and Anti-tumour Immunitysupporting

confidence: 81%

Emerging roles for IL-6 family cytokines as positive and negative regulators of ectopic lymphoid structures

et al. 2021

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“…Interestingly, a retrospective study showed that post-transplantation rituximab did not result in the clearance of intragraft TLTs 58 . Similar findings were consistently reported in other conditions such as autoimmune diseases, 65 – 71 suggesting the importance of the timing of rituximab infusion for controlling TLT formation. Furthermore, patients treated with pretransplantation rituximab maintained similar graft function over 5 years after kidney transplantation, comparable with those who did not, although the immunologic risk was higher in the ABO-incompatible, rituximab-treated group (Supplemental Figure 7).…”

Section: Discussionsupporting

confidence: 59%

Advanced Tertiary Lymphoid Tissues in Protocol Biopsies are Associated with Progressive Graft Dysfunction in Kidney Transplant Recipients

Lee

Sato

Saito

et al. 2022

JASN

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Background: Tertiary lymphoid tissues (TLTs) are ectopic lymphoid tissues found in chronically inflamed organs. Although studies have documented TLT formation in transplanted kidneys, the clinical relevance of these TLTs remains controversial. We examined the impacts of TLTs on future graft function using our histological TLT maturity stages and the association between TLTs and Banff pathologic scores. We also analyzed the risk factors for the development of TLTs Methods: Serial protocol biopsy samples (0-hour, 1-, 6-, and 12-months) without rejection were retrospectively analyzed from 214 patients who underwent living donor kidney transplantation. TLTs were defined as lymphocyte aggregates with signs of proliferation and their stages were determined by the absence (stage I) or presence (stage II) of follicular dendritic cells. Results: Only 4% of patients exhibited TLTs at the 0-hour biopsy. Prevalence increased to almost 50% at the 1-month biopsy and then slightly further for 12 months. The proportion of advanced stage II TLTs increased gradually, reaching 19% at the 12-month biopsy. Presence of stage II TLTs was associated with higher risk of renal function decline after transplantation compared to patients with no TLT or stage I TLTs. Stage II TLTs were associated with more severe tubulitis and interstitial fibrosis/tubular atrophy at 12 months and predicted poorer graft function independently from the degree of interstitial inflammation. Pre-transplantation rituximab treatment dramatically attenuated the development of stage II TLTs. Conclusions: TLTs are commonly found in clinically stable transplanted kidneys. Advanced stage II TLTs are associated with progressive graft dysfunction, independent of interstitial inflammation

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“…Consistently, an increased frequency of lymphocyte-containing tertiary lymphoid structures has been identified in the lungs of CF patients, and chronic bacterial infection has been shown to induce their formation in mice [112]. When the B cell-depleting anti-CD20 antibody rituximab was administered to two CF patients prior to receiving lung transplants, lymphoid aggregates were not disrupted and their role in CF lung pathogenesis could not be determined [113]. Although lymphoid follicle formation can be induced by bacterial lung infection [112] and their presence has been identified in end stage CF [54], further investigation into the role of lymphoid neogenesis in CF is needed to determine if they should be targeted therapeutically [114].…”

Section: B Cellsmentioning

confidence: 99%

Immunomodulation in Cystic Fibrosis: Why and How?

Giacalone

Dobosh

Gaggar

et al. 2020

IJMS

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Cystic fibrosis (CF) lung disease is characterized by unconventional mechanisms of inflammation, implicating a chronic immune response dominated by innate immune cells. Historically, therapeutic development has focused on the mutated cystic fibrosis transmembrane conductance regulator (CFTR), leading to the discovery of small molecules aiming at modulating and potentiating the presence and activity of CFTR at the plasma membrane. However, treatment burden sustained by CF patients, side effects of current medications, and recent advances in other therapeutic areas have highlighted the need to develop novel disease targeting of the inflammatory component driving CF lung damage. Furthermore, current issues with standard treatment emphasize the need for directed lung therapies that could minimize systemic side effects. Here, we summarize current treatment used to target immune cells in the lungs, and highlight potential benefits and caveats of novel therapeutic strategies.

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Peribronchial tertiary lymphoid structures persist after rituximab therapy in patients with cystic fibrosis

Cited by 5 publications

References 9 publications

Emerging roles for IL-6 family cytokines as positive and negative regulators of ectopic lymphoid structures

Emerging roles for IL-6 family cytokines as positive and negative regulators of ectopic lymphoid structures

Advanced Tertiary Lymphoid Tissues in Protocol Biopsies are Associated with Progressive Graft Dysfunction in Kidney Transplant Recipients

Immunomodulation in Cystic Fibrosis: Why and How?

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