Autoimmunity and infection in Sjögren's syndrome

Igoe, Ann; Scofield, R. Hal

doi:10.1097/bor.0b013e32836200d2

Cited by 92 publications

(67 citation statements)

References 87 publications

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“…Antigen mimicry, induced by aberrant EBV exposure or defective immune control, plays a central role in each disease and has been addressed in a number of recent reviews (Ballandraud et al 2004;Pender 2011;Lossius et al 2012;James and Robertson 2012;Füst 2013;Igoe and Scofield 2013). All affected individuals, including the juvenile cases, are EBV seropositive (i.e.…”

Section: Autoimmunity and Antigen Mimicrymentioning

confidence: 97%

Epstein-Barr Virus-Specific Humoral Immune Responses in Health and Disease

Middeldorp

2015

Current Topics in Microbiology and Immunology

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Epstein-Barr virus (EBV) is widely distributed in the world and associated with a still increasing number of acute, chronic, malignant and autoimmune disease syndromes. Humoral immune responses to EBV have been studied for diagnostic, pathogenic and protective (vaccine) purposes. These studies use a range of methodologies, from cell-based immunofluorescence testing to antibody-diversity analysis using immunoblot and epitope analysis using recombinant or synthetic peptide-scanning. First, the individual EBV antigen complexes (VCA , MA, EA(D), EA(R) and EBNA) are defined at cellular and molecular levels, providing a historic overview. The characteristic antibody responses to these complexes in health and disease are described, and differences are highlighted by clinical examples. Options for EBV vaccination are briefly addressed. For a selected number of immunodominant proteins, in particular EBNA1, the interaction with human antibodies is further detailed at the epitope level, revealing interesting insights for structure, function and immunological aspects, not considered previously. Humoral immune responses against EBV-encoded tumour antigens LMP1, LMP2 and BARF1 are addressed, which provide novel options for targeted immunotherapy. Finally, some considerations on EBV-linked autoimmune diseases are given, and mechanisms of antigen mimicry are briefly discussed. Further analysis of humoral immune responses against EBV in health and disease in carefully selected patient cohorts will open new options for understanding pathogenesis of individual EBV-linked diseases and developing targeted diagnostic and therapeutic approaches.

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Section: Autoimmunity and Antigen Mimicrymentioning

confidence: 97%

Epstein-Barr Virus-Specific Humoral Immune Responses in Health and Disease

Middeldorp

2015

Current Topics in Microbiology and Immunology

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“…Patients with MS also have elevated levels of serum IgG Ab against many EBV Ags (35). EBV may also be involved in the salivary gland tissue damage leading to Sjögren's syndrome (36). Data suggesting this possibility include a higher incidence of EBV reactivation in Sjögren's syndrome patients, as well as increased levels of EBV Ag and DNA in salivary-infiltrating lymphocytes (37).…”

Section: Discussionmentioning

confidence: 99%

T Cell Cross-Reactivity between a Highly Immunogenic EBV Epitope and a Self-Peptide Naturally Presented by HLA-B*18:01+ Cells

Hibbert

Croft

Smith

et al. 2015

The Journal of Immunology

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T cell cross-reactivity underpins the molecular mimicry hypothesis in which microbial peptides sharing structural features with host peptides stimulate T cells that cross-react with self-peptides, thereby initiating and/or perpetuating autoimmune disease. EBV represents a potentially important factor in the pathogenesis of several T cell–mediated autoimmune disorders, with molecular mimicry a likely mechanism. In this study, we describe a human self-peptide (DELEIKAY) that is a homolog of a highly immunogenic EBV T cell epitope (SELEIKRY) presented by HLA-B*18:01. This self-peptide was shown to bind stably to HLA-B*18:01, and peptide elution/mass spectrometric studies showed it is naturally presented by this HLA molecule on the surface of human cells. A significant proportion of CD8+ T cells raised from some healthy individuals against this EBV epitope cross-reacted with the self-peptide. A diverse array of TCRs was expressed by the cross-reactive T cells, with variable functional avidity for the self-peptide, including some T cells that appeared to avoid autoreactivity by a narrow margin, with only 10-fold more of the self-peptide required for equivalent activation as compared with the EBV peptide. Structural studies revealed that the self-peptide–HLA-B*18:01 complex is a structural mimic of the EBV peptide–HLA-B*18:01 complex, and that the strong antiviral T cell response is primarily dependent on the alanine/arginine mismatch at position 7. To our knowledge, this is the first report confirming the natural presentation of a self-peptide cross-recognized in the context of self-HLA by EBV-reactive CD8+ T cells. These results illustrate how aberrant immune responses and immunopathological diseases could be generated by EBV infection.

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“…It mainly affects middle-aged women with a female to male ratio ≥ 9:1 [1] [2]. A large number of articles refer to the role of several infections in the pathogenesis of SS and the influence of these infections as a trigger for SS symptoms [3] [4]. However, few of these articles mention the susceptibility of these patients to new infections other than intraoral or ocular infections.…”

mentioning

confidence: 99%

“…However, few of these articles mention the susceptibility of these patients to new infections other than intraoral or ocular infections. Patients with SS have defects in their immune system, such as acquired or inherited complement deficiencies [4] [5], and frequently use immunomodulatory drugs, all of which predispose to bacterial infections. Infections caused by encapsulated organisms or tuberculosis may be those posing a higher risk for SS patients [3] [5] [6].…”

mentioning

confidence: 99%

Increased Susceptibility to Pneumococcal Disease in Sjögren Syndrome Patients

Ercibengoa¹,

Alonso²,

Marimón³

et al. 2014

WJV

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Susceptibility to pneumococcal infections in Sjögren syndrome (SS)-an autoimmune inflammatory disease-patients is not well known, although these patients frequently develop respiratory diseases. The relative risk of developing pneumococcal disease in SS patients versus diabetes mellitus type 2 (DM-2) patients, matched by age, gender, and length of enrolment was studied. From January 1998 to September 2013 the records of Donostia University Hospital were analyzed, which among other patient's data includes: number and type of hospital admissions and number and type of laboratory determinations. Streptococcus pneumoniae isolates of the same serotype causing recurrent infections were characterized by PFGE. The study comprised 127 patients in the SS group (69 primary and 58 secondary) and 127 in the DM-2 group as control. In 12 SS patients, (9.4%) 22 pneumococcal disease episodes were detected. Two patients (1.6%) with a single episode each one were observed among DM-2 patients, p = 0.01, RR for SS patients 6 (95% CI 1.4 to 26.3). No differences could be demonstrated between the two groups of patients in infections caused by Staphylococcus aureus or Streptococcus agalactiae. Most pneumococcal serotypes in SS patients belonged to the 13-valent (50%) and 23-valent (75%) anti-pneumococcal vaccine. SS patients are associated with and increased risk of suffering from pneumococcal disease. Vaccination should be considered in this group of patients.

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Autoimmunity and infection in Sjögren's syndrome

Cited by 92 publications

References 87 publications

Epstein-Barr Virus-Specific Humoral Immune Responses in Health and Disease

Epstein-Barr Virus-Specific Humoral Immune Responses in Health and Disease

T Cell Cross-Reactivity between a Highly Immunogenic EBV Epitope and a Self-Peptide Naturally Presented by HLA-B*18:01+ Cells

Increased Susceptibility to Pneumococcal Disease in Sjögren Syndrome Patients

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Autoimmunity and infection in Sjögren's syndrome

Cited by 92 publications

References 87 publications

Epstein-Barr Virus-Specific Humoral Immune Responses in Health and Disease

Epstein-Barr Virus-Specific Humoral Immune Responses in Health and Disease

T Cell Cross-Reactivity between a Highly Immunogenic EBV Epitope and a Self-Peptide Naturally Presented by HLA-B*18:01+ Cells

Increased Susceptibility to Pneumococcal Disease in Sj&#246;gren Syndrome Patients

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Increased Susceptibility to Pneumococcal Disease in Sjögren Syndrome Patients