EBV/HHV-6A dUTPases contribute to myalgic encephalomyelitis/chronic fatigue syndrome pathophysiology by enhancing TFH cell differentiation and extrafollicular activities.
EBV/HHV-6A dUTPases contribute to myalgic encephalomyelitis/chronic fatigue syndrome pathophysiology by enhancing TFH cell differentiation and extrafollicular activities.
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DOI：
10.1172/jci.insight.158193
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发表时间：
2022-06-08
期刊：
影响因子：
8
通讯作者：
Ariza, Maria Eugenia
中科院分区：
文献类型：
--
作者：
Cox, Brandon S.;Alharshawi, Khaled;Mena-Palomo, Irene;Lafuse, William P.;Ariza, Maria Eugenia
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, debilitating, multisystem illness of unknown etiology for which no cure and no diagnostic tests are available. Despite increasing evidence implicating EBV and human herpesvirus 6A (HHV-6A) as potential causative infectious agents in a subset of patients with ME/CFS, few mechanistic studies address a causal relationship. In this study we examined a large ME/CFS cohort and controls and demonstrated a significant increase in activin A and IL-21 serum levels, which correlated with seropositivity for antibodies against the EBV and HHV-6 protein deoxyuridine triphosphate nucleotidohydrolase (dUTPases) but no increase in CXCL13. These cytokines are critical for T follicular helper (TFH) cell differentiation and for the generation of high-affinity antibodies and long-lived plasma cells. Notably, ME/CFS serum was sufficient to drive TFH cell differentiation via an activin A–dependent mechanism. The lack of simultaneous CXCL13 increase with IL-21 indicates impaired TFH function in ME/CFS. In vitro studies revealed that virus dUTPases strongly induced activin A secretion while in vivo, EBV dUTPase induced the formation of splenic marginal zone B and invariant NKTFH cells. Together, our data indicate abnormal germinal center (GC) activity in participants with ME/CFS and highlight a mechanism by which EBV and HHV6 dUTPases may alter GC and extrafollicular antibody responses.
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DOI：
10.1084/jem.20150282
发表时间：
2016-09-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chorny A;Casas-Recasens S;Sintes J;Shan M;Polentarutti N;García-Escudero R;Walland AC;Yeiser JR;Cassis L;Carrillo J;Puga I;Cunha C;Bastos H;Rodrigues F;Lacerda JF;Morais A;Dieguez-Gonzalez R;Heeger PS;Salvatori G;Carvalho A;Garcia-Sastre A;Blander JM;Mantovani A;Garlanda C;Cerutti A
通讯作者：
Cerutti A
影响因子：
3.7
作者：
Glaser, R;Litsky, ML;Williams, MV
通讯作者：
Williams, MV
影响因子：
6.4
作者：
de Sanjose, Silvia;Bosch, Ramon;Middeldorp, Jaap M.
通讯作者：
Middeldorp, Jaap M.
活化素B作为肌力脑脊髓炎/慢性疲劳综合征（ME/CFS）的临床生物标志物的潜力。
影响因子：
5.5
作者：
Gravelsina S;Nora-Krukle Z;Vilmane A;Svirskis S;Vecvagare K;Krumina A;Murovska M
通讯作者：
Murovska M
影响因子：
3.7
作者：
Wen X;Yang JQ;Kim PJ;Singh RR
通讯作者：
Singh RR