Humoral autoimmunity against endothelium: theory or reality?

Meroni, Pier Luigi; Ronda, Nicoletta; Raschi, Elena; Borghi, Maria Orietta

doi:10.1016/j.it.2005.03.006

Cited by 50 publications

(43 citation statements)

References 70 publications

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“…Mechanisms of liver thrombosis also remain to be clarified. It is tempting to suspect that thrombosis is triggered by endothelial cell damage caused by autoantibody or immune complex, similar to what is proposed as a mechanism of thrombosis in antiphospholipid Ab syndrome (39). Massive cytokine production induced by vaccination can also damage endothelial cells.…”

Section: Discussionmentioning

confidence: 83%

Vaccination-Induced Systemic Autoimmunity in Farmed Atlantic Salmon

Koppang

Bjerkås

Haugarvoll

et al. 2008

The Journal of Immunology

102

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Over half of the salmon consumed globally are farm-raised. The introduction of oil-adjuvanted vaccines into salmon aquaculture made large-scale production feasible by preventing infections. The vaccines that are given i.p. contain oil adjuvant such as mineral oil. However, in rodents, a single i.p. injection of adjuvant hydrocarbon oil induces lupus-like systemic autoimmune syndrome, characterized by autoantibodies, immune complex glomerulonephritis, and arthritis. In the present study, whether the farmed salmon that received oil-adjuvanted vaccine have autoimmune syndrome similar to adjuvant oil-injected rodents was examined. Sera and tissues were collected from vaccinated or unvaccinated Atlantic salmon (experimental, seven farms) and wild salmon. Autoantibodies (immunofluorescence, ELISA, and immunoprecipitation) and IgM levels (ELISA) in sera were measured. Kidneys and livers were examined for pathology. Autoantibodies were common in vaccinated fish vs unvaccinated controls and they reacted with salmon cells/Ags in addition to their reactivity with mammalian Ags. Diffuse nuclear/cytoplasmic staining was common in immunofluorescence but some had more specific patterns. Serum total IgM levels were also increased in vaccinated fish; however, the fold increase of autoantibodies was much more than that of total IgM. Sera from vaccinated fish immunoprecipitated ferritin and ∼50% also reacted with other unique proteins. Thrombosis and granulomatous inflammation in liver, and immune-complex glomerulonephritis were common in vaccinated fish. Autoimmunity similar to the mouse model of adjuvant oil-induced lupus is common in vaccinated farmed Atlantic salmon. This may have a significant impact on production loss, disease of previously unknown etiology, and future strategies of vaccines and salmon farming.

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Section: Discussionmentioning

confidence: 83%

Vaccination-Induced Systemic Autoimmunity in Farmed Atlantic Salmon

Koppang

Bjerkås

Haugarvoll

et al. 2008

The Journal of Immunology

102

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“…The generation of autoAbs cross-reactive with endothelial cells is involved in several autoimmune vascular diseases [33][34][35] . Our studies [23,[36][37][38] showed that Abs directed against DV NS1 cross-reacted with endothelial cells and induced these cells to undergo nitric oxide-mediated apoptosis as well as cytokine and chemokine production.…”

Section: Discussionmentioning

confidence: 99%

C-Terminal Region of Dengue Virus Nonstructural Protein 1 Is Involved in Endothelial Cell Cross-Reactivity via Molecular Mimicry

Wan¹,

Lin²,

Chen³

et al. 2008

American J. of Infectious Diseases

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Infection with dengue virus (DV) causes diseases ranging from self-limited dengue fever to life-threatening dengue hemorrhagic fever and dengue shock syndrome. Vascular leakage, thrombocytopenia and bleeding are the clinical manifestations associated with dengue hemorrhage. We previously showed that anti-DV nonstructural protein 1 (NS1) antibodies (Abs) cross-reacted with endothelial cells. The potential target proteins on endothelial cell surface recognized by anti-DV NS1 Abs showed sequence homology with the C-terminal amino acids (a.a.) 311-352 of DV NS1. In this study, the role of NS1 C-terminal region in dengue autoimmunity was investigated. We deleted the a.a. 277-352 of DV NS1 to prepare truncated NS1 (tNS1) and generated anti-DV tNS1 Abs in mice. The endothelial cell-binding activity of anti-DV tNS1 Abs was lower than that of anti-DV NS1 Abs. In addition, the endothelial cell-binding activity of anti-DV NS1 Abs was inhibited by preabsorption with DV NS1 but not with DV tNS1 proteins. The anti-P311 (a.a. 311-330) and anti-P331 (a.a. 331-350) titers of dengue patient sera were positively correlated with their endothelial cell-binding activity. Dengue patient sera showed lower binding activity to DV tNS1 than to DV NS1 proteins. The endothelial cell-binding activity of dengue patient sera was inhibited by preabsorption with P311 and P331. This study helps to understand the molecular mechanisms of autoimmunity mediated by anti-DV NS1 Abs and to provide the potential implications of tNS1 in dengue vaccine strategies.

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“…Experimentally, a single injection of 2 mg benzopyrene in Sprague-Dawley rats induces a highly malignant sarcoma with a high level of a PI antibodies in serum (30). The antiphospholipid autoantibodies recognize beta2 glycoprotein I adhered to the endothelium and induce a cell perturbation that might underlie the thrombophilic state of the anti-phospholipid syndrome (31). The presence of antiphospholipid antibodies in cancer patients has been proposed as one of the potential mechanisms promoting hypercoagulability (32).…”

Section: Pi Markersmentioning

confidence: 99%

Antiphospholipid Antibodies in Patients with Cancer

Pugliese¹,

Bernardini²,

Pacifico³

et al. 2006

Int J Immunopathol Pharmacol

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Antiphospholipid antibodies are generally associated with Antiphospholipid Syndrome, which can occur as a primary disorder or may be secondary to connective tissue disease or tumour. The presence of antiphospholipid antibodies in patients with tumour disease is responsible for thrombotic complications. In a population of 53 tumor patients with positive carcinoembryonic antigen CEA, carbohydrate antigen CA19.9, CA125 and CA15.3 markers, IgM and IgG anticardiolipin and antiphosphatidylinositol were detected by solid-phase immunoassays. Our results show that moderate or high levels of antiphospholipid antibodies are present in a great number of patients with CEA and CA19.9 markers, suggesting a specific association with gastroenteric tumors. By testing for antiphosphatidylinositol antibodies, many patients not evidenced by the standard anticardiolipin assay were found to be antiphospholipid-positive. The analysis of antiphosphatidylinositol antibodies as a diagnostic tool in gastroenteric cancer to highlight patients with the risk of thromboembolic complications is discussed.

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Humoral autoimmunity against endothelium: theory or reality?

Cited by 50 publications

References 70 publications

Vaccination-Induced Systemic Autoimmunity in Farmed Atlantic Salmon

Vaccination-Induced Systemic Autoimmunity in Farmed Atlantic Salmon

C-Terminal Region of Dengue Virus Nonstructural Protein 1 Is Involved in Endothelial Cell Cross-Reactivity via Molecular Mimicry

Antiphospholipid Antibodies in Patients with Cancer

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