Болезнь Крона, осложненная ВЭБ (Вирус Эпштейн Барр)

Болезнь Крона, осложненная ВЭБ — Вирусом Эпштейн Барр, безуспешно лечили Адалимумаб и 6-меркаптурин. Впервые успешно заменили на монотерапию Rituximab.

Crohn’s disease complicated by Epstein-Barr virus-driven haemophagocytic lymphohistiocytosis successfully treated with rituximab.

Abstract

We report a case of Epstein-Barr virus (EBV)-driven haemophagocytic lymphohistiocytosis (HLH) in a man with Crohn’s disease treated with 6-mercaptopurine and adalimumab therapy who was successfully treated with rituximab therapy alone. This is the first published case in an adult patient with EBV-driven HLH in the setting of thiopurine use and inflammatory bowel disease to be successfully treated with rituximab therapy alone. Here, we will discuss putative immunological mechanisms which may contribute to this potentially life-threatening complication.

PMID:
28228435
DOI:
10.1136/bcr-2016-218578
[Indexed for MEDLINE]

ИСТОЧНИК

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.

KEYWORDS:

Epstein-Barr virus; anti-TNFα; inflammatory bowel disease; lymphomas; lytic activation

PMID:
26307954
DOI:
10.1002/jmv.24331
[Indexed for MEDLINE]

Резюме
Терапия Anti-TNFα, которая, как известно, подавила Т-лимфоцитарный иммунитет, все больше и больше завоевывает популярность для лечения аутоиммунных болезней включая воспалительные заболевания кишечника (ВЗК).

Т-лимфоцитарная супрессия увеличивает риск В-лимфоцитарных ВЭБ-лимфопролиферативных болезней и лимфом.

Так как ВЭБ (Вирус Эпштейн Барр) активация важна для развития ВЭБ-лимфом и были сообщения о ВЭБ-лимфомах, у больных НА anti-TNFα терапии, мы занимались расследованиями, если пациенты относились с anti-TNFα антителами, демонстрируют большую ВЭБ-литическую активность в крови.
Одноядерные клетки периферической крови10 пациентов ВЗК только на МОНО anti-TNFα терапии по сравнению с 3 контрольными группами (10 пациентов ВЗК не на иммунодепрессивной терапии, 10 пациентов с болью в животе, а без ВЗК и 10 здоровых) были исследованы на процент Т-лимфоцитов, груза EBV и EBV-литических транскриптов.

Пациенты на anti-TNFα терапии имели значительно меньше Т-лимфоцитов, большего груза EBV, и увеличили уровни транскриптов от EBV-литических генов всех кинетических классов по сравнению с контрольными группами.

Кроме того, воздействие ВЭБ зараженных В-лимфоцитарных линий к anti-TNFα антителам привело к увеличенным уровням МРНК BZLF1;

BZLF1 кодирует для ЗЕБРЫ, вирусного выключателя цикла времени-ожидания-к-литическому. Таким образом пациенты IBD относились с anti-TNFα антителами, имеют большие грузы EBV, вероятно, из-за расширенной ВЭБ-литической экспрессии гена, и anti-TNFα антитела могут быть достаточными, чтобы активировать литический цикл ВЭБ. Результаты исследования от этого предварительного исследования закладывают основу для дополнительного научного и клинического расследования эффектов anti-TNFα терапии на жизненном цикле ВЭБ, повсеместный oncovirus, который вызывает лимфомы в урегулировании immunocompromise.

ИСТОЧНИК

Вирус Эпштейн Барр, витамин D, CD8+ Т-клетки — участвуют в развитии аутоиммунных заболеваний.

Abstract
CD8+ T-cell deficiency is a feature of many chronic autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, systemic sclerosis, dermatomyositis, primary biliary cirrhosis, primary sclerosing cholangitis, ulcerative colitis, Crohn’s disease, psoriasis, vitiligo, bullous pemphigoid, alopecia areata, idiopathic dilated cardiomyopathy, type 1 diabetes mellitus, Graves’ disease, Hashimoto’s thyroiditis, myasthenia gravis, IgA nephropathy, membranous nephropathy, and pernicious anaemia. It also occurs in healthy blood relatives of patients with autoimmune diseases, suggesting it is genetically determined. Here it is proposed that this CD8+ T-cell deficiency underlies the development of chronic autoimmune diseases by impairing CD8+ T-cell control of Epstein-Barr virus (EBV) infection, with the result that EBV-infected autoreactive B cells accumulate in the target organ where they produce pathogenic autoantibodies and provide costimulatory survival signals to autoreactive T cells which would otherwise die in the target organ by activation-induced apoptosis.


Autoimmunity is postulated to evolve in the following steps:


(1) CD8+ T-cell deficiency,
(2) primary EBV infection,
(3) decreased CD8+ T-cell control of EBV,
(4) increased EBV load and increased anti-EBV antibodies,
(5) EBV infection in the target organ,
(6) clonal expansion of EBV-infected autoreactive B cells in the target organ,
(7) infiltration of autoreactive T cells into the target organ, and
(8) development of ectopic lymphoid follicles in the target organ.


It is also proposed that deprivation of sunlight and vitamin D at higher latitudes facilitates the development of autoimmune diseases by aggravating the CD8+ T-cell deficiency and thereby further impairing control of EBV.
The hypothesis makes predictions which can be tested, including the prevention and successful treatment of chronic autoimmune diseases by controlling EBV infection.

 

 

XXEBV

 

Proposed role of EBV infection in the development of chronic autoimmune diseases. During primary infection EBV infects autoreactive naïve B cells in the tonsil, driving them to enter germinal centres where they proliferate and differentiate into latently infected autoreactive memory B cells (path 1) which then exit from the tonsil and circulate in the blood (path 2). The number of EBV-infected B cells is normally controlled by EBV-specific cytotoxic CD8+ T cells, which kill proliferating and lytically infected B cells, but not if there is a defect in this defence mechanism. Surviving EBV-infected autoreactive memory B cells enter the target organ where they take up residence and produce oligoclonal IgG and pathogenic autoantibodies which attack components of the target organ (path 3). Autoreactive T cells that have been activated in peripheral lymphoid organs by cross-reacting foreign antigens circulate in the blood and enter the target organ where they are reactivated by EBV-infected autoreactive B cells presenting target organ peptides (Tp) bound to major histocompatibility complex (MHC) molecules (path 4). These EBV-infected B cells provide costimulatory survival signals (B7) to the CD28 receptor on the autoreactive T cells and thereby inhibit the activation-induced T-cell apoptosis which normally occurs when autoreactive T cells enter the target organ and interact with nonprofessional antigen-presenting cells (APCs) which do not express B7 costimulatory molecules [168, 169] (Path 6). After the autoreactive T cells have been reactivated by EBV-infected autoreactive B cells, they produce cytokines such as interleukin-2 (IL2), interferon-γ (IFNγ) and tumour necrosis factor-β (TNFβ) and orchestrate an autoimmune attack on the target organ (Path 5). BCR, B cell receptor; TCR, T cell receptor.

XXEBVCROHNS

Proposed sequence of events leading to the development of chronic autoimmune diseases. In individuals with a genetic deficiency of CD8+ T cells (carried by “Autoimmune genes”) and with HLA class II genes predisposing to idiopathic dilated cardiomyopathy (HLA-DR4 [206]), primary biliary cirrhosis (HLA-DR8 [207]), and Crohn’s disease (HLA-DR7 [208]), primary EBV infection, particularly if delayed (Late), leads to the infection of autoreactive B cells, which accumulate in the target organ where they reactivate autoreactive T cells that orchestrate an autoimmune attack on the organ. For simplicity these depictions focus on the role of CD8+ T-cell deficiency, EBV infection and selected HLA alleles and do not include interactions with other genetic and environmental factors that may also contribute to the pathogenesis of autoimmune diseases.

ИСТОЧНИК

Болезнь Крона? Вирус Эпштейн-Барр!!!

Abstract

Epstein-Barr virus (EBV) plays an important role in various diseases. EBV-associated lymphoproliferative disease (LPD) is a rare disease with a canceration tendency. It is difficult to differentiate LPD with involvement of digestive tract from Crohn disease due to similar clinical and endoscopic manifestations. We present a case report of multiple ulcers with esophagus, small bowel and the entire colon involved, proved to be NK-Cell LPD, developed into EBV-associated NK/T Cell lymphoma, in an immunocompetent man who was initially misdiagnosed as Crohn disease.This report underscores that intestinal ulcers should be cautiously diagnosed, for it sometimes could be a precancerous lesion.

ИСТОЧНИК

2 комментария к записи «Болезнь Крона, осложненная ВЭБ (Вирус Эпштейн Барр)»

  1. Пингбэк: Герпес: что с этим делать? | Жизнь с ВЗК (Болезнь Крона)

  2. Пингбэк: Что нужно знать больному ВЗК? | Жизнь с ВЗК (Болезнь Крона)

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