Дифференцирование множественного склероза с доминирующим спинным мозгом и зрительным нервым участием от других аутоиммунных демиелинизирующих заболеваний с использованием клеточного иммунофенотинга и профилирования генного экспрессии.
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Yilmaz Vuslat, Karaaslan Zerrin, Sanli Elif, Yuceer-Korkmaz Hande, Ulusoy Canan Aysel, Timirci-Kahraman Özlem, Gunduz Tuncay, Kurtuncu Murat, Tuncer Asli, Turkoglu Recai, Gursoy-Ozdemir Yasemin, Kucukali Cem Ismail, Tuzun Erdem
Аннотация
Оригинал публикации
Differentiating multiple sclerosis with predominant spinal cord and optic nerve involvement from other autoimmune demyelinating diseases using B cell immunophenotyping and gene expression profiling.
OBJECTIVE: Multiple sclerosis (MS) may present with predominant involvement of the spinal cord and optic nerve (MS/w-SCON) and mimic other autoimmune inflammatory demyelinating disorders (AIDD) such as neuromyelitis optica spectrum disorder (NMOSD), and relapsing inflammatory optic neuritis (RION). Thus, biomarkers are required for effective differential diagnosis of AIDD.
METHODS: Patients with MS/w-SCON (n = 20), MS without involvement of SCON (MS/wo-SCON) (n = 22), NMOSD (n = 16), RION (n = 15) and healthy individuals (n = 21) were included. Peripheral blood cell immunophenotypes were analyzed by flow cytometry and gene expression levels of isolated B cells were assessed by microarray analysis and quantitative real-time PCR.
RESULTS: Significantly increased Breg, plasmablast, and plasma cell ratios distinguished MS/w-SCON from other groups. Most differentially expressed B cell genes were subjected to protein-protein interaction yielding a network of 13 immune mediators (IL18, IL18R1, P2RY12, CSF3R, TNFSF4, TNFRSF13C, TNFRSF1A, CCL20, CCL5, CCR4, CCL4L2, CXCL5, CXCL10). CCL4L2 and CCR4 expression levels distinguished MS/w-SCON. IL18/IL18R1 and CCL5 were distinguishing factors for NMOSD and RION, respectively.
CONCLUSION: Peripheral blood B cell expression levels of CCL4L2, CCR4, IL18, IL18R1 and CCL5 are candidate biomarkers for differential diagnosis of AIDD of CNS. Our results substantiate the significance of B cells in the pathogenesis of these disorders.