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

• Published in: Journal of medical virology 2016-02, Vol.88 (2), p.312-318
• Main Authors: Lapsia, Sameer, Koganti, Siva, Spadaro, Salvatore, Rajapakse, Ramona, Chawla, Anupama, Bhaduri-McIntosh, Sumita
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; anti-TNFα; B-Lymphocytes - virology; Epstein-Barr virus; Female; Gene Expression Profiling; Herpesvirus 4, Human - immunology; Herpesvirus 4, Human - physiology; Humans; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - therapeutic use; inflammatory bowel disease; Inflammatory Bowel Diseases - complications; Inflammatory Bowel Diseases - drug therapy; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - virology; Lymphocyte Count; lymphomas; lytic activation; Male; Middle Aged; Pilot Projects; RNA, Messenger - analysis; RNA, Viral - analysis; T-Lymphocytes - immunology; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Viral Load; Virus Activation - drug effects; Young Adult
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.24331

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. J. Med. Virol. 88:312–318, 2016. © 2015 Wiley Periodicals, Inc.