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CD27(+)CD38(hi) B Cell Frequency During Remission Predicts Relapsing Disease in Granulomatosis With Polyangiitis Patients

Background: Granulomatosis with polyangiitis (GPA) patients are prone to disease relapses. We aimed to determine whether GPA patients at risk for relapse can be identified by differences in B cell subset frequencies. Methods: Eighty-five GPA patients were monitored for a median period of 3.1 years (...

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Autores principales: von Borstel, Anouk, Land, Judith, Abdulahad, Wayel H., Rutgers, Abraham, Stegeman, Coen A., Diepstra, Arjan, Heeringa, Peter, Sanders, Jan Stephan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769172/
https://www.ncbi.nlm.nih.gov/pubmed/31608054
http://dx.doi.org/10.3389/fimmu.2019.02221
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author von Borstel, Anouk
Land, Judith
Abdulahad, Wayel H.
Rutgers, Abraham
Stegeman, Coen A.
Diepstra, Arjan
Heeringa, Peter
Sanders, Jan Stephan
author_facet von Borstel, Anouk
Land, Judith
Abdulahad, Wayel H.
Rutgers, Abraham
Stegeman, Coen A.
Diepstra, Arjan
Heeringa, Peter
Sanders, Jan Stephan
author_sort von Borstel, Anouk
collection PubMed
description Background: Granulomatosis with polyangiitis (GPA) patients are prone to disease relapses. We aimed to determine whether GPA patients at risk for relapse can be identified by differences in B cell subset frequencies. Methods: Eighty-five GPA patients were monitored for a median period of 3.1 years (range: 0.1–6.3). Circulating B cell subset frequencies were analyzed by flow cytometry determining the expression of CD19, CD38, and CD27. B cell subset frequencies at the time of inclusion of future-relapsing (F-R) and non-relapsing (N-R) patients were compared and related to relapse-free survival. Additionally, CD27(+)CD38(hi) B cells were assessed in urine and kidney biopsies from active anti-neutrophil cytoplasmic autoantibody-associated vasculitides (AAV) patients with renal involvement. Results: Within 1.6 years, 30% of patients experienced a relapse. The CD27(+)CD38(hi) B cell frequency at the time of inclusion was increased in F-R (median: 2.39%) compared to N-R patients (median: 1.03%; p = 0.0025) and a trend was found compared with the HCs (median: 1.33%; p = 0.08). This increased CD27(+)CD38(hi) B cell frequency at inclusion was correlated to decreased relapse-free survival in GPA patients. In addition, 74.7% of patients with an increased CD27(+)CD38(hi) B cell frequency (≥2.39%) relapsed during follow-up compared to 19.7% of patients with a CD27(+)CD38(hi) B cell frequency of <2.39%. No correlations were found between CD27(+)CD38(hi) B cells and ANCA levels. CD27(+)CD38(hi) B cell frequencies were increased in urine compared to the circulation, and were also detected in kidney biopsies, which may indicate CD27(+)CD38(hi) B cell migration during active disease. Conclusions: Our data suggests that having an increased frequency of circulating CD27(+)CD38(hi) B cells during remission is related to a higher relapse risk in GPA patients, and therefore might be a potential marker to identify those GPA patients at risk for relapse.
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spelling pubmed-67691722019-10-11 CD27(+)CD38(hi) B Cell Frequency During Remission Predicts Relapsing Disease in Granulomatosis With Polyangiitis Patients von Borstel, Anouk Land, Judith Abdulahad, Wayel H. Rutgers, Abraham Stegeman, Coen A. Diepstra, Arjan Heeringa, Peter Sanders, Jan Stephan Front Immunol Immunology Background: Granulomatosis with polyangiitis (GPA) patients are prone to disease relapses. We aimed to determine whether GPA patients at risk for relapse can be identified by differences in B cell subset frequencies. Methods: Eighty-five GPA patients were monitored for a median period of 3.1 years (range: 0.1–6.3). Circulating B cell subset frequencies were analyzed by flow cytometry determining the expression of CD19, CD38, and CD27. B cell subset frequencies at the time of inclusion of future-relapsing (F-R) and non-relapsing (N-R) patients were compared and related to relapse-free survival. Additionally, CD27(+)CD38(hi) B cells were assessed in urine and kidney biopsies from active anti-neutrophil cytoplasmic autoantibody-associated vasculitides (AAV) patients with renal involvement. Results: Within 1.6 years, 30% of patients experienced a relapse. The CD27(+)CD38(hi) B cell frequency at the time of inclusion was increased in F-R (median: 2.39%) compared to N-R patients (median: 1.03%; p = 0.0025) and a trend was found compared with the HCs (median: 1.33%; p = 0.08). This increased CD27(+)CD38(hi) B cell frequency at inclusion was correlated to decreased relapse-free survival in GPA patients. In addition, 74.7% of patients with an increased CD27(+)CD38(hi) B cell frequency (≥2.39%) relapsed during follow-up compared to 19.7% of patients with a CD27(+)CD38(hi) B cell frequency of <2.39%. No correlations were found between CD27(+)CD38(hi) B cells and ANCA levels. CD27(+)CD38(hi) B cell frequencies were increased in urine compared to the circulation, and were also detected in kidney biopsies, which may indicate CD27(+)CD38(hi) B cell migration during active disease. Conclusions: Our data suggests that having an increased frequency of circulating CD27(+)CD38(hi) B cells during remission is related to a higher relapse risk in GPA patients, and therefore might be a potential marker to identify those GPA patients at risk for relapse. Frontiers Media S.A. 2019-09-24 /pmc/articles/PMC6769172/ /pubmed/31608054 http://dx.doi.org/10.3389/fimmu.2019.02221 Text en Copyright © 2019 von Borstel, Land, Abdulahad, Rutgers, Stegeman, Diepstra, Heeringa and Sanders. http://creativecommons.org/licenses/by/4.0/ 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) and the copyright owner(s) 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.
spellingShingle Immunology
von Borstel, Anouk
Land, Judith
Abdulahad, Wayel H.
Rutgers, Abraham
Stegeman, Coen A.
Diepstra, Arjan
Heeringa, Peter
Sanders, Jan Stephan
CD27(+)CD38(hi) B Cell Frequency During Remission Predicts Relapsing Disease in Granulomatosis With Polyangiitis Patients
title CD27(+)CD38(hi) B Cell Frequency During Remission Predicts Relapsing Disease in Granulomatosis With Polyangiitis Patients
title_full CD27(+)CD38(hi) B Cell Frequency During Remission Predicts Relapsing Disease in Granulomatosis With Polyangiitis Patients
title_fullStr CD27(+)CD38(hi) B Cell Frequency During Remission Predicts Relapsing Disease in Granulomatosis With Polyangiitis Patients
title_full_unstemmed CD27(+)CD38(hi) B Cell Frequency During Remission Predicts Relapsing Disease in Granulomatosis With Polyangiitis Patients
title_short CD27(+)CD38(hi) B Cell Frequency During Remission Predicts Relapsing Disease in Granulomatosis With Polyangiitis Patients
title_sort cd27(+)cd38(hi) b cell frequency during remission predicts relapsing disease in granulomatosis with polyangiitis patients
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769172/
https://www.ncbi.nlm.nih.gov/pubmed/31608054
http://dx.doi.org/10.3389/fimmu.2019.02221
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