Conventional memory B, T cells potential biomarkers for juvenile dermatomyositis
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Conventional memory B cells with low CXCR5 levels and CXCR5 T-helper 2 memory cells are potential biomarkers of juvenile dermatomyositis disease activity, according to data published in Arthritis & Rheumatology.
“Overall, our findings add new insights towards cellular correlates of juvenile dermatomyositis disease activity and provide novel pathogenic clues,” Jacqueline Gofshteyn, MD, of the department of pediatrics at Weill Cornell Medical College, in New York, and colleagues wrote. “They also expand the list of diseases, mainly autoimmune but also virally-induced, where extrafollicular pathways appear dysregulated.”
To identify markers of juvenile dermatomyositis disease activity, Gofshteyn and colleagues performed laboratory tests, including manual muscle testing, the Childhood Myositis Assessment Scale and Disease Activity Scores. Additionally, they used flow cytometry to determine the surface phenotype of peripheral blood mononuclear cells, and RNA-sequencing/microarrays to assess whole blood transcriptional profiles. Participants included 123 patients with juvenile dermatomyositis patients and 53 healthy control individuals enrolled at four different pediatric hospitals.
Participants were organized into three main cohorts. Both the initial cohort, which included 35 patients with juvenile dermatomyositis and 10 healthy controls, and a validation cohort with 45 patients and 14 healthy controls, were analyzed for flow cytometry immunophenotyping. The initial cohort was also assessed for blood samples necessary for RNA-sequencing. Meanwhile, a third cohort of 26 patients with active juvenile dermatomyositis, 17 with inactive juvenile dermatomyositis and 25 healthy controls was studied via microarray technology for gene expression profiling validation.
According to the researchers, there was an expansion of T-helper 2 memory cells within the CXCR5 memory CD4 T-cell compartment in both the initial (P = .05) and validation (P < .0001) cohorts. Additionally, the frequency of conventional memory B cells with low CXCR5 (CXCR5lo-) were correlated with aldolase in both the initial (P < .01) and validation (P = .02) cohorts, as well as muscle weakness in the initial (P = .005) and validation (P = .02) cohorts.
The frequency of conventional memory B cells with low CXCR5 were correlated with multiple interferon stimulated gene mean modular scores, according to researchers. Transitional B cells were also expanded (P = .049) in juvenile dermatomyositis.
“Here, we report that in addition to transitional B-cells, CXCR5lo- conventional memory B-cells are expanded in juvenile dermatomyositis blood, and their frequency correlates with clinical and laboratory markers of muscle disease activity, including aldolase, Childhood Myositis Assessment Scale, and manual muscle testing in two independent cohorts of patients,” Gofshteyn and colleagues wrote.
“Our findings add to prior work examining the phenotype of juvenile dermatomyositis peripheral blood mononuclear cells by highlighting a potential extrafollicular interaction between CXCR5lo- conventional memory B-cells and CD4+ T-helper 2 cells,” they added. “The links between these CXCR5lo- T and B-cell populations, their roles at local inflammatory sites, and their interactions with interferon pathways in the context of juvenile dermatomyositis pathogenesis remain important questions to address.”
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Gofshteyn JS, et al. Arthritis Rheumatol. 2022;doi:10.1002/art.42446.
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