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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Inflammation
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1437767
This article is part of the Research Topic Immunological Aspects of Fibrosis Pathogenesis: Novel Mechanisms and Therapeutic Strategies View all 6 articles

Tertiary Lymphoid Structures and B-cell infiltration are IPF features with functional consequences

Provisionally accepted
Elisabetta Cocconcelli Elisabetta Cocconcelli 1Elisabetta Balestro Elisabetta Balestro 1Graziella Turato Graziella Turato 1Giordano Fiorentù Giordano Fiorentù 1Erica Bazzan Erica Bazzan 1Davide Biondini Davide Biondini 1Mariaenrica Tinè Mariaenrica Tinè 1Nicol Bernardinello Nicol Bernardinello 1Federica Pezzuto Federica Pezzuto 1Simonetta Baraldo Simonetta Baraldo 1Fiorella Calabrese Fiorella Calabrese 1FEDERICO REA FEDERICO REA 1Alessandro Sanduzzi Zamparelli Alessandro Sanduzzi Zamparelli 2Paolo Spagnolo Paolo Spagnolo 1Manuel G. Cosio Manuel G. Cosio 3Marina Saetta Marina Saetta 1*
  • 1 University of Padua, Padua, Italy
  • 2 Federico II University Hospital, Naples, Campania, Italy
  • 3 McGill University, Montreal, Quebec, Canada

The final, formatted version of the article will be published soon.

    Background. Recent literature has shown the presence of B-cells and autoantibodies in IPF which would imply the presence of Tertiary Lymphoid Structures (TLS, sites where the immune response is triggered), yet TLS are not considered features of the histological characteristics of IPF.Aim. To quantify presence, size and degree of activation of TLS in biopsied and explanted-lungs from patients with early and late IPF, never treated with antifibrotics, and relate their presence and activity to the clinical course, disease progression and lung inflammation.Methods. Immunochemistry for B-cells, CD4, CD8 and CD45 cells was performed in lung tissue from IPF patients, 18 at diagnosis (early), 39 explanted (end-stage) and 12 smoking controls. TLS activation was assessed by CD40 expression. Spirometry along 31(12-72) months of follow-up was used to characterize end-stage IPF as slowprogressors or rapid-progressors.Results. B-cells along with other inflammatory cells were higher in early and end-stage IPF than in controls (p<0.001). In rapid-progressors all inflammatory cells were higher than in slow-progressors (p<0.05). TLS were present in 100% of early and end-stage IPF and in 50% of controls. In end-stage IPF, TLS area and activation-score were higher than in early IPF (p<0.0001; p=0.005) and controls (p<0.04; p<0.002). TLS activation score correlated with FVC decline during follow-up in rapid-progressors (r=0.73; p=0.007) but not in slow-progressors.A prominent B-cell infiltration along with the presence of TLS, which activity correlates with FVC-decline, are important components of IPF from the beginning of the disease, likely playing an important role on its mechanism and progression.

    Keywords: Autoimmunity, B-cell, Early IPF, IPF progression, Tertiary Lymphoid Follicles, CD40

    Received: 24 May 2024; Accepted: 19 Sep 2024.

    Copyright: © 2024 Cocconcelli, Balestro, Turato, Fiorentù, Bazzan, Biondini, Tinè, Bernardinello, Pezzuto, Baraldo, Calabrese, REA, Sanduzzi Zamparelli, Spagnolo, Cosio and Saetta. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Marina Saetta, University of Padua, Padua, Italy

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