Epstein-Barr Virus and Rheumatoid Arthritis

Lotz, Martin; Roudier, Jean

doi:10.1007/978-3-642-76189-8_18

“…However, since we could not show absence of such a link in individuals without SS but with reactivation of EBV, it is questionable whether the link observed is indeed significant to SS patients. In fact, it has been reported that the reactivation of EBV is not a SS-specific event (62) and that a relationship between some populations of autoimmune diseases and EBV reactivation is present (63,64), but anti-␣-fodrin Ab is a SS-specific autoantibody (16,65). Furthermore, it cannot be detected in plasma of rheumatoid arthritis and systemic lupus erythematosus patients (16,65) even in the plasma of these patients with EBV reactivation (H. Inoue and I. Saito, unpublished observations).…”

Section: Discussionmentioning

confidence: 99%

Possible Involvement of EBV-Mediated α-Fodrin Cleavage for Organ-Specific Autoantigen in Sjogren’s Syndrome

Inoue

¹

,

Tsubota

²

,

Ono

³

et al. 2001

The Journal of Immunology

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A cleavage product of α-fodrin may be an important organ-specific autoantigen in the pathogenesis of Sjogren’s syndrome (SS), but the mechanisms of α-fodrin cleavage remain unclear. Since EBV has been implicated in the pathogenesis of SS, we determined whether EBV activation could induce the SS-specific 120-kDa autoantigen α-fodrin. ZEBRA mRNA expression, a marker for activation of the lytic cycle of EBV, was found in the salivary gland tissues from SS patients, but not in those from control individuals. ZEBRA-expressing lymphoid cells were also found in the SS glands in double-stained immunohistochemistry. Furthermore, a significant link between production of Abs against 120-kDa α-fodrin and reactivated EBV Ag was found in sera from patients with SS, but not in those from control individuals. EBV-activated lymphoid cells showed specific α-fodrin cleavage to the expected 120-kDa fragments in vitro. Pretreatment with caspase inhibitors inhibited cleavage of α-fodrin. Thus, an increase in apoptotic protease activities induced by EBV reactivation may be involved in the progression of α-fodrin proteolysis in the development of SS.

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“…Shown are only viral proteins recognized at least once in a given HLA context. bodies in RA patients, by frequently increased EBV loads in patients' plasma during late stages of the disease and by the existence of cross-reactivity between EBV and articular components [1,[4][5][6][7][8][9][10]. However, in the absence of any conclusive data demonstrating an increased prevalence of EBV in RA lesions [11][12][13], it has been difficult to establish direct causal links between the above EBVassociated alterations and RA pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

Frequent enrichment for CD8 T cells reactive against common herpes viruses in chronic inflammatory lesions: towards a reassessment of the physiopathological significance of T cell clonal expansions found in autoimmune inflammatory processes

Scotet¹,

Peyrat²,

Saulquin³

et al. 1999

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We recently evidenced a dramatic enrichment for T cells reactive against Epstein-Barr virus (EBV) within inflamed joints of two rheumatoid arthritis patients. To assess the generality of this phenomenon and its relevance to autoimmunity, we studied the responses of CD8 T cells from patients with either acute or chronic inflammatory diseases (rheumatoid arthritis: n = 18, ankylosing spondylitis: n = 5, psoriatic arthritis: n = 4, Reiter's syndrome: n = 3, arthrosis: n = 2, uveitis: n = 2, multiple sclerosis: n = 2, encephalitis: n = 1) against viral proteins derived from EBV and another common herpes virus, human cytomegalovirus (CMV). T cell responses against EBV and/or CMV epitopes were frequently observed within CD8 T cells derived from chronic inflammatory lesions, irrespective of their location (knee, eye, brain) and autoimmune features. In most cases, CD8 T cells derived from affected organs yielded stronger anti-viral T cell responses than CD8 T cells derived from patients' PBL, even in chronic inflammatory diseases devoid of autoimmune features or induced by defined bacterial agents. Taken together, these results suggest that the presence of virus-specific T cells within inflamed lesions of patients suffering from autoimmune diseases is a general phenomenon associated with chronic inflammation rather than the initiating cause of the autoimmune process. Since this phenomenon was sometimes associated with long-term T repertoire biases within inflamed lesions, the physiopathological significance of T cell clonal expansions found in a recurrent fashion within chronically inflamed autoimmune lesions should be interpreted with caution.

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“…For instance, an association between common viruses such as EBV and RA was suggested by the presence of a higher frequency and higher levels of EBV-specific anti- Figure 1. bodies in RA patients, by frequently increased EBV loads in patients' plasma during late stages of the disease and by the existence of cross-reactivity between EBV and articular components [1,[4][5][6][7][8][9][10]. Results are expressed as pg/ml TNF- § released by 10 5 , 10 4 , and 10 3 CD8 + T cells derived from PBL ( 1 ) or synovial fluid lymphocytes ( AE ) after a 6-h incubation with COS cells transiently cotransfected with DNA coding for a given HLA/viral protein combination.…”

Section: Introductionmentioning

confidence: 99%

Frequent enrichment for CD8 T cells reactive against common herpes viruses in chronic inflammatory lesions: towards a reassessment of the physiopathological significance of T cell clonal expansions found in autoimmune inflammatory processes

Scotet

¹

,

Peyrat

²

,

Saulquin

³

et al. 1999

View full text Add to dashboard Cite

We recently evidenced a dramatic enrichment for T cells reactive against Epstein-Barr virus (EBV) within inflamed joints of two rheumatoid arthritis patients. To assess the generality of this phenomenon and its relevance to autoimmunity, we studied the responses of CD8 T cells from patients with either acute or chronic inflammatory diseases (rheumatoid arthritis: n = 18, ankylosing spondylitis: n = 5, psoriatic arthritis: n = 4, Reiter's syndrome: n = 3, arthrosis: n = 2, uveitis: n = 2, multiple sclerosis: n = 2, encephalitis: n = 1) against viral proteins derived from EBV and another common herpes virus, human cytomegalovirus (CMV). T cell responses against EBV and/or CMV epitopes were frequently observed within CD8 T cells derived from chronic inflammatory lesions, irrespective of their location (knee, eye, brain) and autoimmune features. In most cases, CD8 T cells derived from affected organs yielded stronger anti-viral T cell responses than CD8 T cells derived from patients' PBL, even in chronic inflammatory diseases devoid of autoimmune features or induced by defined bacterial agents. Taken together, these results suggest that the presence of virus-specific T cells within inflamed lesions of patients suffering from autoimmune diseases is a general phenomenon associated with chronic inflammation rather than the initiating cause of the autoimmune process. Since this phenomenon was sometimes associated with long-term T repertoire biases within inflamed lesions, the physiopathological significance of T cell clonal expansions found in a recurrent fashion within chronically inflamed autoimmune lesions should be interpreted with caution.

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Epstein-Barr Virus and Rheumatoid Arthritis

Cited by 5 publications

References 120 publications

Possible Involvement of EBV-Mediated α-Fodrin Cleavage for Organ-Specific Autoantigen in Sjogren’s Syndrome

Possible Involvement of EBV-Mediated α-Fodrin Cleavage for Organ-Specific Autoantigen in Sjogren’s Syndrome

Frequent enrichment for CD8 T cells reactive against common herpes viruses in chronic inflammatory lesions: towards a reassessment of the physiopathological significance of T cell clonal expansions found in autoimmune inflammatory processes

Frequent enrichment for CD8 T cells reactive against common herpes viruses in chronic inflammatory lesions: towards a reassessment of the physiopathological significance of T cell clonal expansions found in autoimmune inflammatory processes

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