Increase of circulating memory B cells after glucocorticoid-induced remission identifies patients at risk of IgG4-related disease relapse

M Lanzillotta, E Della-Torre, R. Milani, E Bozzolo, E Bozzalla-Cassione, L Rovati, PG Arcidiacono, S Partelli, M Falconi, F Ciceri, L Dagna

Research output: Contribution to journalArticle

Abstract

Background: Immunoglobulin G4-related disease (IgG4-RD) promptly responds to glucocorticoids but relapses in a considerable fraction of patients. Reliable biomarkers of flare are currently lacking because the pathophysiology of IgG4-RD remains largely elusive. In the present work, we aimed to identify perturbations of B-cell subpopulations that might predict IgG4-RD relapse. Methods: Thirty patients were treated with glucocorticoids according to international guidelines. Circulating CD19+and CD20+cells, naive B cells, memory B cells, plasmablasts, and plasma cells were measured by flow cytometry at baseline and every 6 months for 2 years after the initiation of corticosteroid therapy. Results: Patients with active untreated IgG4-RD showed significantly reduced CD19+B cells, CD20+B cells, and naive B cells compared with healthy subjects (p <0.05), but significantly expanded plasmablasts and plasma cells (p <0.01). After 6 months of corticosteroid treatment, all patients achieved clinical improvement. Naive B cells, plasmablasts, and plasma cells significantly decreased compared with disease onset, whereas memory B cells significantly increased compared with baseline (p <0.01). Increase of memory B cells was observed only in patients who relapsed within 2 years of follow-up, however (HR, 12.24; 2.99 to 50.2; p = 0.0005). In these patients, the relapse rates at 12 and 24 months were 30% and 100%, respectively. No abnormalities of other B-cell subpopulations at disease onset or after 6 months of glucocorticoid treatment were found to predict IgG4-RD relapse at 2 years. Conclusions: Increase of circulating memory B cells after 6 months of glucocorticoid treatment might predict IgG4-RD relapse. © 2018 The Author(s).
Original languageEnglish
Article number222
JournalArthritis Research and Therapy
Volume20
DOIs
Publication statusPublished - 2018

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Glucocorticoids
B-Lymphocytes
Immunoglobulin G
Recurrence
Immunoglobulins
Plasma Cells
Adrenal Cortex Hormones
Therapeutics
Healthy Volunteers
Flow Cytometry
Biomarkers
Guidelines

Cite this

@article{b800f4fc591a49a590c35e7ed7c5862a,
title = "Increase of circulating memory B cells after glucocorticoid-induced remission identifies patients at risk of IgG4-related disease relapse",
abstract = "Background: Immunoglobulin G4-related disease (IgG4-RD) promptly responds to glucocorticoids but relapses in a considerable fraction of patients. Reliable biomarkers of flare are currently lacking because the pathophysiology of IgG4-RD remains largely elusive. In the present work, we aimed to identify perturbations of B-cell subpopulations that might predict IgG4-RD relapse. Methods: Thirty patients were treated with glucocorticoids according to international guidelines. Circulating CD19+and CD20+cells, naive B cells, memory B cells, plasmablasts, and plasma cells were measured by flow cytometry at baseline and every 6 months for 2 years after the initiation of corticosteroid therapy. Results: Patients with active untreated IgG4-RD showed significantly reduced CD19+B cells, CD20+B cells, and naive B cells compared with healthy subjects (p <0.05), but significantly expanded plasmablasts and plasma cells (p <0.01). After 6 months of corticosteroid treatment, all patients achieved clinical improvement. Naive B cells, plasmablasts, and plasma cells significantly decreased compared with disease onset, whereas memory B cells significantly increased compared with baseline (p <0.01). Increase of memory B cells was observed only in patients who relapsed within 2 years of follow-up, however (HR, 12.24; 2.99 to 50.2; p = 0.0005). In these patients, the relapse rates at 12 and 24 months were 30{\%} and 100{\%}, respectively. No abnormalities of other B-cell subpopulations at disease onset or after 6 months of glucocorticoid treatment were found to predict IgG4-RD relapse at 2 years. Conclusions: Increase of circulating memory B cells after 6 months of glucocorticoid treatment might predict IgG4-RD relapse. {\circledC} 2018 The Author(s).",
author = "M Lanzillotta and E Della-Torre and R. Milani and E Bozzolo and E Bozzalla-Cassione and L Rovati and PG Arcidiacono and S Partelli and M Falconi and F Ciceri and L Dagna",
year = "2018",
doi = "10.1186/s13075-018-1718-5",
language = "English",
volume = "20",
journal = "Arthritis Research and Therapy",
issn = "1478-6354",
publisher = "BioMed Central",

}

TY - JOUR

T1 - Increase of circulating memory B cells after glucocorticoid-induced remission identifies patients at risk of IgG4-related disease relapse

AU - Lanzillotta, M

AU - Della-Torre, E

AU - Milani, R.

AU - Bozzolo, E

AU - Bozzalla-Cassione, E

AU - Rovati, L

AU - Arcidiacono, PG

AU - Partelli, S

AU - Falconi, M

AU - Ciceri, F

AU - Dagna, L

PY - 2018

Y1 - 2018

N2 - Background: Immunoglobulin G4-related disease (IgG4-RD) promptly responds to glucocorticoids but relapses in a considerable fraction of patients. Reliable biomarkers of flare are currently lacking because the pathophysiology of IgG4-RD remains largely elusive. In the present work, we aimed to identify perturbations of B-cell subpopulations that might predict IgG4-RD relapse. Methods: Thirty patients were treated with glucocorticoids according to international guidelines. Circulating CD19+and CD20+cells, naive B cells, memory B cells, plasmablasts, and plasma cells were measured by flow cytometry at baseline and every 6 months for 2 years after the initiation of corticosteroid therapy. Results: Patients with active untreated IgG4-RD showed significantly reduced CD19+B cells, CD20+B cells, and naive B cells compared with healthy subjects (p <0.05), but significantly expanded plasmablasts and plasma cells (p <0.01). After 6 months of corticosteroid treatment, all patients achieved clinical improvement. Naive B cells, plasmablasts, and plasma cells significantly decreased compared with disease onset, whereas memory B cells significantly increased compared with baseline (p <0.01). Increase of memory B cells was observed only in patients who relapsed within 2 years of follow-up, however (HR, 12.24; 2.99 to 50.2; p = 0.0005). In these patients, the relapse rates at 12 and 24 months were 30% and 100%, respectively. No abnormalities of other B-cell subpopulations at disease onset or after 6 months of glucocorticoid treatment were found to predict IgG4-RD relapse at 2 years. Conclusions: Increase of circulating memory B cells after 6 months of glucocorticoid treatment might predict IgG4-RD relapse. © 2018 The Author(s).

AB - Background: Immunoglobulin G4-related disease (IgG4-RD) promptly responds to glucocorticoids but relapses in a considerable fraction of patients. Reliable biomarkers of flare are currently lacking because the pathophysiology of IgG4-RD remains largely elusive. In the present work, we aimed to identify perturbations of B-cell subpopulations that might predict IgG4-RD relapse. Methods: Thirty patients were treated with glucocorticoids according to international guidelines. Circulating CD19+and CD20+cells, naive B cells, memory B cells, plasmablasts, and plasma cells were measured by flow cytometry at baseline and every 6 months for 2 years after the initiation of corticosteroid therapy. Results: Patients with active untreated IgG4-RD showed significantly reduced CD19+B cells, CD20+B cells, and naive B cells compared with healthy subjects (p <0.05), but significantly expanded plasmablasts and plasma cells (p <0.01). After 6 months of corticosteroid treatment, all patients achieved clinical improvement. Naive B cells, plasmablasts, and plasma cells significantly decreased compared with disease onset, whereas memory B cells significantly increased compared with baseline (p <0.01). Increase of memory B cells was observed only in patients who relapsed within 2 years of follow-up, however (HR, 12.24; 2.99 to 50.2; p = 0.0005). In these patients, the relapse rates at 12 and 24 months were 30% and 100%, respectively. No abnormalities of other B-cell subpopulations at disease onset or after 6 months of glucocorticoid treatment were found to predict IgG4-RD relapse at 2 years. Conclusions: Increase of circulating memory B cells after 6 months of glucocorticoid treatment might predict IgG4-RD relapse. © 2018 The Author(s).

U2 - 10.1186/s13075-018-1718-5

DO - 10.1186/s13075-018-1718-5

M3 - Article

VL - 20

JO - Arthritis Research and Therapy

JF - Arthritis Research and Therapy

SN - 1478-6354

M1 - 222

ER -