scholarly journals Syk-Induced Phosphatidylinositol-3-Kinase Activation in Epstein-Barr Virus Posttransplant Lymphoproliferative Disorder

2013 ◽  
Vol 13 (4) ◽  
pp. 883-890 ◽  
Author(s):  
O. Hatton ◽  
S. L. Lambert ◽  
L. K. Phillips ◽  
M. Vaysberg ◽  
Y. Natkunam ◽  
...  
2019 ◽  
Vol 29 (2) ◽  
pp. 185-193 ◽  
Author(s):  
Michelle Liu ◽  
Shahid Husain ◽  
Olusegun Famure ◽  
Yanhong Li ◽  
S. Joseph Kim

Background: Posttransplant lymphoproliferative disorder (PTLD) is a severe complication after kidney transplantation. This study examined the incidence, risk factors, clinical management, and outcomes of PTLD in a cohort of kidney transplant recipients. Design: This single-center cohort study included 1642 patients transplanted from January 1, 2000, to December 31, 2012, with follow-up until December 31, 2013. The incidence and risk factors for PTLD were examined using a Cox proportional hazards model. A Cox model was also used to assess the association of PTLD and graft outcomes. Results: Sixteen recipients developed PTLD over follow-up. The incidence rate was 0.18 (95% confidence interval [CI]: 0.11-0.29) cases per 100 person-years. Four were from Epstein–Barr virus (EBV) mismatched (D+/R−) transplants and 12 from EBV-positive recipients (R+). Recipients with D+/R− matches were at a significantly higher risk of developing PTLD than R+ (hazard ratio [HR]: 7.52 [95% CI: 2.42-23.32]). Fifteen cases had immunosuppression reduced, 11 cases were supplemented with rituximab or ganciclovir, 6 cases required chemotherapy or radiation, and 6 cases had tumors excised. By the end of follow-up, 6 patients went into remission, 5 returned to chronic dialysis, and 5 patients died. Patients with PTLD were significantly more likely to have total graft failure (return to chronic dialysis, preemptive retransplant, or death with graft function) than patients without PTLD (HR: 3.41 [95% CI: 1.72-6.78). Discussion: Epstein–Barr virus mismatch continues to be a strong risk factor for developing PTLD after kidney transplantation. Recipients with PTLD have a poor prognosis, as the optimal management remains to be elucidated.


2001 ◽  
Vol 75 (13) ◽  
pp. 6135-6142 ◽  
Author(s):  
Catherine Dayle Darr ◽  
Amy Mauser ◽  
Shannon Kenney

ABSTRACT Expression of the Epstein-Barr virus (EBV) immediate-early (IE) protein BRLF1 induces the lytic form of viral replication in most EBV-positive cell lines. BRLF1 is a transcriptional activator that binds directly to a GC-rich motif present in some EBV lytic gene promoters. However, BRLF1 activates transcription of the other IE protein, BZLF1, through an indirect mechanism which we previously showed to require activation of the stress mitogen-activated protein kinases. Here we demonstrate that BRLF1 activates phosphatidylinositol-3 (PI3) kinase signaling in host cells. We show that the specific PI3 kinase inhibitor, LY294002, completely abrogates the ability of a BRLF1 adenovirus vector to induce the lytic form of EBV infection, while not affecting lytic infection induced by a BZLF1 adenovirus vector. Furthermore, we demonstrate that the requirement for PI3 kinase activation in BRLF1-induced transcriptional activation is promoter dependent. BRLF1 activation of the SM early promoter (which occurs through a direct binding mechanism) does not require PI3 kinase activation, whereas activation of the IE BZLF1 and early BMRF1 promoters requires PI3 kinase activation. Thus, there are clearly two separate mechanisms by which BRLF1 induces transcriptional activation.


2013 ◽  
Vol 30 (3) ◽  
pp. 315-320 ◽  
Author(s):  
Saime Paydaş ◽  
Semra Paydaş ◽  
Mustafa Balal ◽  
Arbil Açıkalın ◽  
Melek Ergin ◽  
...  

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