TY - JOUR
T1 - Association of Juvenile Dermatomyositis Disease Activity With the Expansion of Blood Memory B and T Cell Subsets Lacking Follicular Markers
AU - Gofshteyn, Jacqueline S.
AU - Mansfield, Leanne
AU - Spitznagle, Jacob
AU - Balasubramanian, Preetha
AU - Cardenas, Jacob
AU - Miller, Thomas
AU - Gu, Jinghua
AU - Wang, Xuan
AU - Punaro, Marilynn
AU - Fuller, Julie
AU - Nassi, Lorien
AU - Stewart, Katie
AU - Ohouo, Marina
AU - Stagnar, Cristy
AU - Baisch, Jeanine
AU - Walters, Lynnette
AU - Wang, Yuanyuan
AU - Yan, Helena
AU - Rinchai, Darawan
AU - Chaussabel, Damien
AU - Caielli, Simone
AU - Hong, Seunghee
AU - Onel, Karen
AU - Wright, Tracey
AU - Pascual, Virginia
N1 - Publisher Copyright:
© 2023 American College of Rheumatology.
PY - 2023/7
Y1 - 2023/7
N2 - Objective: This study was undertaken to identify blood markers of juvenile dermatomyositis (DM) disease activity (DA), which are needed to improve disease management. Methods: The study comprised a total of 123 juvenile DM patients and 53 healthy controls. Results of laboratory tests (aldolase, creatinine kinase, lactate dehydrogenase [LDH], aspartate aminotransferase) and clinical measures of DA in patients with juvenile DM, including the Manual Muscle Testing in 8 muscles (MMT-8), Childhood Myositis Assessment Scale (CMAS), and disease activity scores (DAS) (total DAS for juvenile DM, the muscle DAS, and the skin DAS), were recorded when available. Surface phenotype of peripheral blood mononuclear cells was assessed using flow cytometry. Whole blood transcriptional profiles were studied using either RNA-sequencing or microarrays. Differential gene expression was determined using DESeq and compared by pathway and gene ontology analyses. Results: Conventional memory (CD27+IgD–) B cells expressing low CXCR5 levels (CXCR5low/– CM B cells) were significantly increased in frequency and absolute numbers in 2 independent cohorts of juvenile DM patients compared with healthy controls. The frequency of CD4+ Th2 memory cells (CD45RA–CXCR5–CCR6–CXCR3–) was also increased in juvenile DM, especially in patients who were within <1 year from diagnosis. The frequency of CXCR5low/– CM B cells correlated with serum aldolase levels and with a blood interferon-stimulated gene transcriptional signature. Furthermore, both the frequency and absolute numbers of CXCR5low/– CM B cells correlated with clinical and laboratory measures of muscle DA (MMT-8, CMAS, aldolase, and LDH). Conclusion: These findings suggest that both CM B cells lacking the CXCR5 follicular marker and CXCR5– Th2 cells represent potential biomarkers of DA in juvenile DM and may contribute to its pathogenesis.
AB - Objective: This study was undertaken to identify blood markers of juvenile dermatomyositis (DM) disease activity (DA), which are needed to improve disease management. Methods: The study comprised a total of 123 juvenile DM patients and 53 healthy controls. Results of laboratory tests (aldolase, creatinine kinase, lactate dehydrogenase [LDH], aspartate aminotransferase) and clinical measures of DA in patients with juvenile DM, including the Manual Muscle Testing in 8 muscles (MMT-8), Childhood Myositis Assessment Scale (CMAS), and disease activity scores (DAS) (total DAS for juvenile DM, the muscle DAS, and the skin DAS), were recorded when available. Surface phenotype of peripheral blood mononuclear cells was assessed using flow cytometry. Whole blood transcriptional profiles were studied using either RNA-sequencing or microarrays. Differential gene expression was determined using DESeq and compared by pathway and gene ontology analyses. Results: Conventional memory (CD27+IgD–) B cells expressing low CXCR5 levels (CXCR5low/– CM B cells) were significantly increased in frequency and absolute numbers in 2 independent cohorts of juvenile DM patients compared with healthy controls. The frequency of CD4+ Th2 memory cells (CD45RA–CXCR5–CCR6–CXCR3–) was also increased in juvenile DM, especially in patients who were within <1 year from diagnosis. The frequency of CXCR5low/– CM B cells correlated with serum aldolase levels and with a blood interferon-stimulated gene transcriptional signature. Furthermore, both the frequency and absolute numbers of CXCR5low/– CM B cells correlated with clinical and laboratory measures of muscle DA (MMT-8, CMAS, aldolase, and LDH). Conclusion: These findings suggest that both CM B cells lacking the CXCR5 follicular marker and CXCR5– Th2 cells represent potential biomarkers of DA in juvenile DM and may contribute to its pathogenesis.
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U2 - 10.1002/art.42446
DO - 10.1002/art.42446
M3 - Article
C2 - 36648920
AN - SCOPUS:85163784773
SN - 2326-5191
VL - 75
SP - 1246
EP - 1261
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
IS - 7
ER -