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EBV and rheumatoid arthritis

Gaetane Nocturne, Saida Boudaoud, Bineta Ly, Juliette Pascaud, Audrey Paoletti, Xavier Mariette
OBJECTIVES: Rheumatoid arthritis (RA) is associated with an increased risk of lymphoma linked to activity of the disease. Immunosuppressive drugs have been suspected to induce an additional risk. Since, NK cells have been recently shown to participate to anti-lymphoma immunosurveillance, we aimed to assess if anti-TNF might impact their anti-lymphoma activity. METHODS: NK cells have been assessed ex vivo in patients with RA treated with methotrexate (MTX) with or without anti-TNF...
February 14, 2017: Journal of Autoimmunity
Nathalie Balandraud, Gaetan Texier, Emmanuel Massy, Olivier Muis-Pistor, Marielle Martin, Isabelle Auger, Marie-Caroline Guzian, Sandrine Guis, Thao Pham, Jean Roudier
BACKGROUND: Epstein-Barr Virus (EBV) is a widely disseminated lymphotropic herpes virus implicated in benign and malignant disorders. In transplant patients, immunosuppressive drugs (cyclosporine) diminish control of EBV replication, potentially leading to lymphoproliferative disorders (LPD). Rheumatoid arthritis (RA) patients have impaired control of EBV infection and have EBV load ten times higher than controls. As post transplant patients, patients with RA have increased risk of developing lymphomas...
2017: PloS One
Alvise Berti, Mara Felicetti, Susanna Peccatori, Roberto Bortolotti, Anna Guella, Paolo Vivaldi, Luca Morelli, Mattia Barabareschi, Giuseppe Paolazzi
OBJECTIVES: Epstein-Barr virus (EBV) is involved in the pathogenesis of approximately 40% of lymphoproliferative disorders (LPDs) arising in patients receiving immunosuppressive treatment (IST) for rheumatic diseases, but data from large cohorts are still not available. We aimed to identify clinicopathological features, management and outcome of this condition. METHODS: We reviewed all published cases of EBV-encoded RNA (EBER)-positive LPDs and included in our analysis one unpublished patient diagnosed in our Hospital...
February 11, 2017: Joint, Bone, Spine: Revue du Rhumatisme
Louise Sternbæk, Anette H Draborg, Christoffer T Nielsen, Søren Jacobsen, Line V Iversen, Lone Troelsen, Elke Theander, Gunnar Houen
BACKGROUND: Collection and testing of individual serum samples are often used in research to gain knowledge about e.g. the humoral response against bacteria or virus. This is a valid but time-consuming method and might be a waste of valuable serum samples for inefficient research. So far, no study has considered using serum pools as a quick and efficient screening method to confirm or deny hypotheses. METHODS: We created serum pools from four different patient groups (systemic lupus erythematosus n=85, rheumatoid arthritis n=77, Sjögren's syndrome n=91, systemic sclerosis n=66) and one healthy control group (n=67)...
January 25, 2017: Journal of Immunological Methods
Kohei Kano 鹿野耕平, Takayuki Katayama, Shiori Takeguchi, Asuka Asanome, Kae Takahashi, Tsukasa Saito, Jun Sawada, Masato Saito, Ryogo Anei, Kyousuke Kamada, Naoyuki Miyokawa, Hiroshi Nishihara, Naoyuki Hasebe
A 75-year-old woman was admitted to our hospital with rapidly deteriorating consciousness disturbance. She had a 7-year history of rheumatoid arthritis (RA), which had been treated with methotrexate (MTX) and prednisolone. Brain T2-weighted MRI showed diffuse high-intensity lesions in the cerebral subcortical and deep white matter, bilateral basal ganglia and thalamus. A cerebrospinal fluid examination revealed elevated protein levels and positive Epstein-Barr virus (EBV) DNA. Human immunodeficiency virus was negative...
December 22, 2016: Neuropathology: Official Journal of the Japanese Society of Neuropathology
Kozue Ejima-Yamada, Yumi Oshiro, Seiichi Okamura, Tomoaki Fujisaki, Yasuhito Mihashi, Kazuo Tamura, Tomoko Fukushige, Masaru Kojima, Kazutoshi Shibuya, Morishige Takeshita
We analyzed CpG-island hypermethylation status in 12 genes of paraffin-embedded tissues from 38 rheumatoid arthritis (RA) patients with methotrexate (MTX)-associated large B cell lymphoproliferative disorder (BLPD), 11 RA patients with non-MTX-associated BLPD (non-MTX-BLPD), 22 controls with diffuse large B cell lymphoma (DLBCL), and 10 controls with Epstein-Barr virus (EBV)(+) DLBCL. Among them, tumor cells from EBV(+) MTX-BLPD patients and control EBV(+) DLBCL patients had significantly lower median incidence of CpG island methylator phenotype (CIMP) than those from non-MTX-BLPD and control DLBCL groups (2...
February 2017: Virchows Archiv: An International Journal of Pathology
Takayuki Katsuyama, Ken-Ei Sada, Minglu Yan, Sonia Zeggar, Sumie Hiramatsu, Yoshia Miyawaki, Keiji Ohashi, Michiko Morishita, Haruki Watanabe, Eri Katsuyama, Mariko Takano-Narazaki, Noriko Toyota-Tatebe, Katsue Sunahori-Watanabe, Tomoko Kawabata, Kohei Miyake, Toru Kiguchi, Jun Wada
OBJECTIVES: To determine prognostic factors of methotrexate-associated lymphoproliferative disorder (MTX-LPD) and evaluate the efficacy and safety of biological therapy in rheumatoid arthritis (RA) complicated with MTX-LPD. METHODS: Thirty RA patients who developed MTX-LPD were investigated in this study. We compared the clinical and laboratory parameters of patients who achieved regression of LPD by MTX withdrawal with those who required chemotherapy and evaluated the clinical course of RA after LPD development...
December 15, 2016: Modern Rheumatology
Anna Dittfeld, Katarzyna Gwizdek, Marek Michalski, Romuald Wojnicz
The Epstein-Barr virus (EBV), also known as human herpesvirus 4, is a member of the Herpesviridae virus family. EBV infection can cause infectious mononucleosis (IM) in the lytic phase of EBV's life cycle. Past EBV infection is associated with lymphomas, and may also result in certain allergic and autoimmune diseases. Although potential mechanisms of autoimmune diseases have not been clearly elucidated, both genetic and environmental factors, such as infectious agents, are considered to be responsible for their development...
2016: Central-European Journal of Immunology
Michael D Chang, Merry-Jennifer Markham, Xiuli Liu
The link between immunosuppressive therapy and increased lymphoma risk is well established in patients with solid organ transplantation. Epstein-Barr virus-positive (EBV) diffuse large B-cell lymphoma (DLBCL) is known to be a complication in patients receiving methotrexate for rheumatoid arthritis, and the risk of lymphoma in inflammatory bowel disease (IBD) has raised concerns regarding the lymphoproliferative potential of immunomodulatory therapy. In this report, we describe a case of EBV-positive DLBCL arising within the colon of a patient affected by ulcerative pancolitis...
October 2016: Gastroenterology Research
Wederson M Claudino, Bradley Gibson, William Tse, Maxwell Krem, Jaspreet Grewal
Methotrexate (MTX) is a commonly used anti-metabolite agent. Increased risk of lymphoproliferative disorders (LPD) in patients with rheumatoid arthritis (RA) has been documented with the prolonged use of immunosuppressive medications such as MTX. This is thought to be the result of immune dysregulation and/or chronic immune stimulation. Most cases of LPDs regress following withdrawal of the offending immunosuppressive agent. We present an interesting and rare case of CD30 and EBV positive CD8 primary cutaneous anaplastic large cell lymphoma (PC-ALCL) in a 66-year-old African American woman...
2016: American Journal of Blood Research
Chiaki Oe, Miki Hiraoka, Sachie Tanaka, Hiroshi Ohguro
Acute retinal necrosis (ARN) is a rapidly progressive and severe retinitis resulting in a poor visual outcome. Infections caused by herpes viruses such as herpes simplex virus (HSV) types 1 and 2 or the varicella zoster virus (VZV) are known to be implicated in the development of ARN. In the present study, an 80-year-old female with ARN was examined. She had been affected with rheumatoid arthritis and had taken methotrexate for over 10 years. Her right eye showed clinical features of ARN, and her left eye showed mild retinitis...
January 2016: Case Reports in Ophthalmology
Mostafa Mahabadi, Ebrahim Faghihiloo, Gholam Hossein Alishiri, Mohamad Hossein Ataee, Ramezan Ali Ataee
INTRODUCTION: Rheumatoid arthritis (RA) is one of the most common chronic inflammatory disorders. Genes and environmental factors contribute to RA. Epstein-Barr Virus (EBV) has been considered as one the RA pathogeneses. The aim of this study was to detect of the EBV genome in patients with RA. METHODS: In this cross-sectional study, 50 samples of synovial fluid were obtained from patients with RA from 2010-2012. Using a standard of the EBV genome and EBNA-1-specific primers, the method of PCR was set up...
March 2016: Electronic Physician
Yuka Kobayashi, Kazuhiro Kimura, Youichiro Fujitsu, Kuniisa Shinkawa, Hiroko Muta, Koh-Hei Sonoda
PURPOSE: Lymphoproliferative disorders (LPDs) can develop in patients treated with methotrexate (MTX) and usually respond well to MTX withdrawal. Mucosa-associated lymphoid tissue (MALT) lymphoma is a relatively rare type of MTX-LPD. The development of MTX-LPD in the orbit has not been previously described. We here report a case of orbital MALT lymphoma that disappeared after MTX withdrawal in a patient treated with MTX for rheumatoid arthritis. CASE: A 78-year-old woman who complained of swelling of the left upper eyelid had been treated with MTX for >8 years for rheumatoid arthritis...
May 2016: Japanese Journal of Ophthalmology
Anette Draborg, Jose M G Izarzugaza, Gunnar Houen
PURPOSE OF REVIEW: Systemic lupus erythematosus (SLE) is caused by a combination of genetic and acquired immunodeficiencies and environmental factors including infections. An association with Epstein-Barr virus (EBV) has been established by numerous studies over the past decades. Here, we review recent experimental studies on EBV, and present our integrated theory of SLE development. RECENT FINDINGS: SLE patients have dysfunctional control of EBV infection resulting in frequent reactivations and disease progression...
July 2016: Current Opinion in Rheumatology
Pooja Adtani, Narasimhan Malathi
CONTEXT: Pathogenesis of autoimmune diseases (AD) is one of a multifactorial milieu. A genetic predisposition, an immune system failure, hormonal imbalance and environmental factors play important roles. Among the many environmental factors, the role of infection is gaining importance in the pathogenesis of various autoimmune disorders; among them, Epstein-Barr virus (EBV) plays a pivotal role. Literature states an association of various AD with EBV namely multiple sclerosis, autoimmune thyroiditis, systemic lupus erythematous, oral lichen planus (OLP), rheumatoid arthritis (RA), autoimmune hepatitis, Sjögren's syndrome and Kawasaki disease; among these, the most commonly occurring are OLP and RA...
September 2015: Journal of Oral and Maxillofacial Pathology: JOMFP
Masakazu Fujimoto, Yo Kaku, Noriyuki Yamakawa, Daisuke Kawabata, Koichiro Ohmura, Itsuko Koyanagi, Tsuneyo Mimori, Kenji Kabashima, Hironori Haga
Rheumatoid vasculitis (RV) is one of the most serious extra-articular complications of rheumatoid arthritis (RA), generally treated with a high dose of immunosuppressive drugs. Recently, we encountered two cases of ulcerative vasculitis in methotrexate (MTX)-prescribed RA patients, which simulated RV; however, Epstein-Barr virus (EBV)-encoded RNA in situ hybridization on their skin biopsies revealed many EBV-positive lymphocytes (over 50 cells/high-power field) within the vessel walls and perivascular stroma, which led us to the diagnosis of EBV-related vasculitis instead of RV...
June 2016: Journal of Cutaneous Pathology
Takefumi Katsuragi, Atsushi Iwashige, Junichi Tsukada
An increased risk of lymphoproliferative disorders (LPD) has been demonstrated in patients treated with methotrexate (MTX) for rheumatoid arthritis (RA). The role of Epstein-Barr virus (EBV) has been discussed in the pathogenesis of immunodeficiency-associated LPDs. We herein present a RA patient, who developed Burkitt lymphoma during MTX treatment. The patient was a 61-year-old Japanese female with a 10-year history of weekly MTX therapy for RA. She presented with a one-month history of submandibular lymph node swelling and fever...
January 2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Cindy Mourgues, Cecile Henquell, Zuzana Tatar, Bruno Pereira, Cinthya Nourisson, Anne Tournadre, Martin Soubrier, Marion Couderc
INTRODUCTION: IL-6 is involved in viral immunosurveillance. We studied the effect of tocilizumab (TCZ) on the evolution in viral load (VL) for the Epstein-Barr virus (EBV), cytomegalovirus (CMV) and varicella-zoster virus (VZV) in patients with rheumatoid arthritis (RA). METHODS: EBV, CMV and VZV loads were prospectively determined in whole blood of 22 RA patients at TCZ initiation and during treatment follow-up. A difference of 0.5 log10 or of threefold copies/mL between two VL was considered significant...
July 2016: Joint, Bone, Spine: Revue du Rhumatisme
Yuichi Makino, Chikayoshi Tani, Naoyuki Miyokawa, Ryota Yoshimoto, Katsutoshi Mizumoto, Kohei Eguchi, Daisuke Fujishiro, Satoru Kodama, Atsushi Kobayashi, Keiji Komura, Kensaku Okamoto, Hiroyuki Furukawa, Masakazu Haneda
A 47-year-old woman with a 2-year history of rheumatoid arthritis (RA) undergoing methotrexate treatment developed a perforated ulcer in the ileum for which she underwent emergency surgery. A histological analysis of the extirpated specimen presented a possible Epstein-Barr virus (EBV) infection in the ulcerative lesion without a feature of lymphoproliferative disorder. Interestingly, the patient's serological tests with a paired serum diagnosed a primary EBV infection. The present case emphasizes the importance of being aware of severe enteritis as a possibility for patients with RA, for an accurate diagnosis...
2015: Internal Medicine
Detlev Schultze, Bernhard Mani, Günter Dollenmaier, Roland Sahli, Andrea Zbinden, Pierre Alexandre Krayenbühl
BACKGROUND: Hepatitis E virus (HEV) is the most recently discovered of the hepatotropic viruses, and is considered an emerging pathogen in developed countries with the possibility of fulminant hepatitis in immunocompromised patients. Especially in the latter elevated transaminases should be taken as a clue to consider HEV infection, as it can be treated by discontinuation of immunosuppression and/or ribavirin therapy. To our best knowledge, this is a unique case of autochthonous HEV infection with coincident reactivation of Epstein-Barr virus (EBV) infection in an immunosuppressed patient with rheumatoid arthritis (RA)...
2015: BMC Infectious Diseases
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