TY - JOUR
T1 - B-cell receptor profiling before and after IVIG monotherapy in newly diagnosed idiopathic inflammatory myopathies
AU - Anang, Dornatien C.
AU - Walter, Hannah A. W.
AU - Lim, Johan
AU - Niewold, Ilse
AU - van der Weele, Linda
AU - Aronica, Eleonora
AU - Eftimov, Filip
AU - Raaphorst, Joost
AU - van Schaik, Barbera D. C.
AU - van Kampen, Antoine H. C.
AU - van der Kooi, Anneke J.
AU - de Vries, Niek
N1 - Funding Information: All patients were included in a study evaluating the effect of immunoglobulins as a first line treatment [], which was funded by a grant (Interlaken Leadership Award) from CSL Behring. The funder had no role in the design of the original study, the analysis, collection and interpretation of the data, and writing of the manuscript. The research leading to these results has received funding via a grant from ‘Stichting Remmert Adriaan Laan Fonds’. D.C.A. and N.dV. were funded by the Horizon 2020 project COSMIC ( www.cosmic-h2020.eu ) under the Marie Skłodowska-Curie grant agreement No. 765158. This work was carried out on the Dutch national e-infrastructure with the support of SURF Foundation (e-infra180005). Publisher Copyright: © 2022 The Author(s). Published by Oxford University Press on behalf of the British Society for Rheumatology.
PY - 2023/7/1
Y1 - 2023/7/1
N2 - Objective: To unravel B-cell receptor (BcR) characteristics in muscle tissues and peripheral blood and gain more insight into BcR repertoire changes in peripheral blood in idiopathic inflammatory myopathies (IIMs), and study how this correlates to the clinical response to IVIG. Methods: Nineteen treatment-naive patients with newly diagnosed IIM were prospectively treated with IVIG monotherapy. RNA-based BcR repertoire sequencing was performed in muscle biopsies collected before, and in peripheral blood (PB) collected before and nine weeks after IVIG treatment. Results were correlated to patients' clinical improvement based on the total improvement score (TIS). Results: Prior to IVIG treatment, BcR clones found in muscle tissue could be retrieved in peripheral blood. Nine weeks after IVIG treatment, new patient-specific dominant BcR clones appeared in peripheral blood while pre-treatment dominant BcR clones disappeared. The cumulative frequency of all dominant BcR clones before treatment was significantly higher in individuals who responded to IVIG compared with those who did not respond to IVIG, and correlated with a higher CK. During follow-up, a decrease in the cumulative frequency of all dominant clones correlated with a higher TIS. Conclusion: In treatment-naive patients with newly diagnosed IIM, muscle tissue and peripheral blood share expanded BcR clones. In our study a higher cumulative frequency of dominant BcR clones in blood before treatment was associated with a higher CK and better treatment response, suggesting that response to IVIG may depend on the composition of the pre-treatment BcR repertoire.
AB - Objective: To unravel B-cell receptor (BcR) characteristics in muscle tissues and peripheral blood and gain more insight into BcR repertoire changes in peripheral blood in idiopathic inflammatory myopathies (IIMs), and study how this correlates to the clinical response to IVIG. Methods: Nineteen treatment-naive patients with newly diagnosed IIM were prospectively treated with IVIG monotherapy. RNA-based BcR repertoire sequencing was performed in muscle biopsies collected before, and in peripheral blood (PB) collected before and nine weeks after IVIG treatment. Results were correlated to patients' clinical improvement based on the total improvement score (TIS). Results: Prior to IVIG treatment, BcR clones found in muscle tissue could be retrieved in peripheral blood. Nine weeks after IVIG treatment, new patient-specific dominant BcR clones appeared in peripheral blood while pre-treatment dominant BcR clones disappeared. The cumulative frequency of all dominant BcR clones before treatment was significantly higher in individuals who responded to IVIG compared with those who did not respond to IVIG, and correlated with a higher CK. During follow-up, a decrease in the cumulative frequency of all dominant clones correlated with a higher TIS. Conclusion: In treatment-naive patients with newly diagnosed IIM, muscle tissue and peripheral blood share expanded BcR clones. In our study a higher cumulative frequency of dominant BcR clones in blood before treatment was associated with a higher CK and better treatment response, suggesting that response to IVIG may depend on the composition of the pre-treatment BcR repertoire.
KW - B cells
KW - B-cell receptor sequencing
KW - Idiopathic inflammatory myopathy
KW - intravenous immunoglobulin
UR - http://www.scopus.com/inward/record.url?scp=85164239296&partnerID=8YFLogxK
U2 - https://doi.org/10.1093/rheumatology/keac602
DO - https://doi.org/10.1093/rheumatology/keac602
M3 - Article
C2 - 36321862
SN - 1462-0324
VL - 62
SP - 2585
EP - 2593
JO - Rheumatology (Oxford, England)
JF - Rheumatology (Oxford, England)
IS - 7
ER -