| Title | Juvenile dermatomyositis disease activity is associated with the expansion of blood B and T-cell memory subsets lacking follicular markers. |
| Publication Type | Journal Article |
| Year of Publication | 2023 |
| Authors | Gofshteyn J, Mansfield L, Spitznagle J, Balasubramanian P, Cardenas J, Miller T, Gu J, Wang X, Punaro M, Fuller J, Nassi L, Stewart K, Ohouo M, Stagnar C, Baisch J, Walters L, Wang Y, Yan H, Rinchai D, Chaussabel D, Caielli S, Hong S, Onel K, Wright T, Pascual V |
| Journal | Arthritis Rheumatol |
| Date Published | 2023 Jan 17 |
| ISSN | 2326-5205 |
| Abstract | OBJECTIVES: To identify markers of Juvenile Dermatomyositis (JDM) disease activity (DA), which are needed to improve disease management. METHODS: 123 JDM patients and 53 healthy controls (HC) were included in the study. Laboratory tests (aldolase, CK, LDH, AST) and clinical measures of DA, including the Manual Muscle Testing (MMT-8), Childhood Myositis Assessment Scale (CMAS), and Disease Activity Scores (DAS), were recorded when available. Surface phenotype of peripheral blood mononuclear cells (PBMCs) was assessed using flow cytometry. Whole blood transcriptional profiles were studied using either RNA-sequencing or microarrays. Differential gene expression was analyzed using DESeq2, pathway, and gene ontology. RESULTS: Conventional memory (CD27+ IgD- ) B-cells expressing low CXCR5 levels (CXCR5lo/- CM B-cells) were significantly increased in frequency and absolute numbers in two independent cohorts of JDM patients compared with HC. The frequency of CD4+ T-helper 2 memory (Th2) cells (CD45RA- CXCR5- CCR6- CXCR3- ) was also increased, especially in patients <1 year from diagnosis. CXCR5lo/- CM B-cell frequency correlated with serum aldolase levels and with a blood interferon (IFN)-stimulated gene (ISG) transcriptional signature, while both the frequency and absolute cell numbers of CXCR5lo/- CM B-cells correlated with clinical and laboratory measures of muscle DA (MMT-8, CMAS, aldolase, and LDH). CONCLUSIONS: Our findings suggest that conventional memory B-cells lacking the CXCR5 follicular marker and CXCR5- Th2 cells represent potential biomarkers of JDM DA and may contribute to JDM pathogenesis. |
| DOI | 10.1002/art.42446 |
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| Alternate Journal | Arthritis Rheumatol |
| PubMed ID | 36648920 |