Anti‐TNFα therapy for inflammatory bowel diseases is associated with Epstein‐Barr virus lytic activation

Abstract

Anti-TNFα therapy, known to suppress T-cell immunity, is increasingly gaining popularity for treatment of autoimmune diseases including inflammatory bowel diseases (IBD). T-cell suppression increases the risk of B-cell EBV-lymphoproliferative diseases and lymphomas. Since EBV-lytic activation is essential for development of EBV-lymphomas and there have been reports of EBV-lymphomas in patients treated with anti-TNFα therapy, we investigated if patients treated with anti-TNFα antibodies demonstrate greater EBV-lytic activity in blood. Peripheral blood mononuclear cells from 10 IBD patients solely on anti-TNFα therapy compared to 3 control groups (10 IBD patients not on immunosuppressive therapy, 10 patients with abdominal pain but without IBD, and 10 healthy subjects) were examined for the percentage of T-cells, EBV load and EBV-lytic transcripts. Patients on anti-TNFα therapy had significantly fewer T-cells, greater EBV load, and increased levels of transcripts from EBV-lytic genes of all kinetic classes compared to controls. Furthermore, exposure of EBV-infected B-cell lines to anti-TNFα antibodies resulted in increased levels of BZLF1 mRNA; BZLF1 encodes for ZEBRA, the viral latency-to-lytic cycle switch. Thus, IBD patients treated with anti-TNFα antibodies have greater EBV loads likely due to enhanced EBV-lytic gene expression and anti-TNFα antibodies may be sufficient to activate the EBV lytic cycle. Findings from this pilot study lay the groundwork for additional scientific and clinical investigation into the effects of anti-TNFα therapy on the life cycle of EBV, a ubiquitous oncovirus that causes lymphomas in the setting of immunocompromise.

Inhalation treatment of primary lung cancer using liposomal curcumin dry powder inhalers

“…Tumor necrosis factor- α (TNF- α ), malondialdehyde (MDA) and caspase-3 are the important markers reflecting immune responses, oxidation and apoptosis, respectively 31 . The concentration of TNF- α in the BALFs was measured with the corresponding enzyme-linked immunosorbent assay (ELISA) kits and caspase-3 in the lung cancer tissues was measured using a caspase-3 activity assay kit (KeyGEN BioTECH Corp., China).…”

Systematic review: hepatosplenic T‐cell lymphoma on biologic therapy for inflammatory bowel disease, including data from the Food and Drug Administration Adverse Event Reporting System

“…Four patients on anti‐TNF therapy had an active EBV infection at the time of HSTCL diagnosis. Anti‐TNF therapy is known to cause lytic activation of EBV which may support a mechanistic hypothesis for the development of HSTCL; however, whether EBV infection is necessary for the development of HSTCL in this patient population is unknown. It is also unknown whether differences in baseline serologic positivity might affect the risk of developing HSTCL.…”

The Impact of Human Herpesviruses in Clinical Practice of Inflammatory Bowel Disease in the Era of COVID-19

“…As patients receiving hematopoietic stem cell transplantation are also known to be at high risk of reactivation of EBV, close monitoring of EBV viral load has been recommended [70]. In patients with IBD, elderly patients and those taking infliximab are a risk factor for the presence of EBV DNA in blood [71,72]. On the other hand, several studies focusing on CD described that treatment with azathioprine and/or anti-TNF-α antibodies did not influence the EBV viral load [73,74].…”