Altered immune landscape of cervical lymph nodes reveals Epstein-Barr virus signature in multiple sclerosis

被引：1

作者：

Sarkkinen, Joona ^{[1
]}

Yohannes, Dawit A. ^{[1
]}

Kreivi, Nea ^{[1
]}

Duernsteiner, Pia ^{[1
]}

Elsakova, Alexandra ^{[1
]}

Huuhtanen, Jani ^{[1
,2
,3
,4
,5
]}

Nowlan, Kirsten ^{[1
]}

Kurdo, Goran ^{[6
,7
]}

Linden, Riikka ^{[6
,7
]}

Saarela, Mika ^{[8
]}

Tienari, Pentti J. ^{[1
,8
]}

Kekaelaeinen, Eliisa ^{[1
]}

Perdomo, Maria ^{[7
,9
]}

Laakso, Sini M. ^{[1
,8
]}

机构：

[1] Univ Helsinki, Translat Immunol Res Program, Helsinki, Finland

[2] Univ Helsinki, Dept Hematol, Hematol Res Unit Helsinki, Helsinki, Finland

[3] Helsinki Univ Hosp, Comprehens Canc Ctr, Helsinki, Finland

[4] Univ Helsinki, ICAN Digital Precis Canc Med Flagship, Helsinki, Finland

[5] Aalto Univ, Sch Sci, Dept Comp Sci, Espoo, Finland

[6] Univ Helsinki, Dept Radiol, Helsinki, Finland

[7] Helsinki Univ Hosp, Helsinki, Finland

[8] Helsinki Univ Hosp, Brain Ctr, Dept Neurol, Helsinki, Finland

[9] Univ Helsinki, Dept Virol, Helsinki, Finland

来源：

SCIENCE IMMUNOLOGY | 2025年 / 10卷 / 104期

基金：

芬兰科学院;

关键词：

GERMINAL CENTER; T-CELLS; B-CELLS; DIFFERENTIATION; INFECTION; RESPONSES; SELECTION; DATABASE; CENTERS; EGRESS;

D O I：

10.1126/sciimmunol.adl3604

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, and Epstein-Barr virus (EBV) infection is a prerequisite for developing the disease. However, the pathogenic mechanisms that lead to MS remain to be determined. Here, we characterized the immune landscape of deep cervical lymph nodes (dcLNs) in newly diagnosed untreated patients with MS (pwMS) using fine-needle aspirations. By combining single-cell RNA sequencing and cellular indexing of transcriptomes and epitopes by sequencing, we observed increased memory B cells and reduced germinal center B cells with decreased clonality in pwMS. Double-negative memory B cells were increased in pwMS that transcriptionally resembled B cells with a lytic EBV infection. Moreover, EBV-targeting memory CD8 T cells were detected in a subset of pwMS. We also detected increased EBV DNA in dcLNs and elevated viral loads in patient saliva. These findings suggest that EBV-driven B cell dysregulation is a critical mechanism in MS pathogenesis.

引用

页数：15

共 111 条

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