Common infectious agents prevalence in antiphospholipid syndrome

Zinger, H.; Sherer, Yaniv; Goddard, Gisele Zandman; Berkun, Yackov; Barzilai, Ori; Agmon‐Levin, Nancy; Ram, Maya; Blank, Miri; Tincani, Anǵela; Rozman, B; Cervera, Ricard; Shoenfeld, Yehuda

doi:10.1177/0961203309345738

Cited by 40 publications

(22 citation statements)

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“…2,3 Patients with persistent aPLAs only occasionally present with thrombotic episodes, and sometimes bacterial or viral infections are associated with the clinical manifestations. 4 These observations suggest that the presence of aPLAs alone is not sufficient to promote thrombosis. Most likely, a priming factor of infectious or inflammatory origin is needed.…”

mentioning

confidence: 77%

Toll-like receptor 2 mediates the activation of human monocytes and endothelial cells by antiphospholipid antibodies

Satta¹,

Kruithof²,

Fickentscher³

et al. 2011

Blood

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IntroductionThe antiphospholipid antibody syndrome (APS) is characterized by clinical manifestations such as arterial or venous thromboembolism and/or recurrent pregnancy complications, as well as the presence of antiphospholipid antibodies (aPLAs). 1 Endothelial cells, monocytes, and platelets are targeted by aPLAs, and inflammatory activation of these cells has been proposed as a pathogenic mechanism. aPLAs are composed of heterogenous auto-antibodies that recognize plasma proteins bound to phospholipid surfaces. One antigenic target of aPLAs is the plasma phospholipid-binding protein ␤2-glycoprotein 1 (␤2GP1), which has been detected on the surface of endothelial cells and monocytes. 2,3 Patients with persistent aPLAs only occasionally present with thrombotic episodes, and sometimes bacterial or viral infections are associated with the clinical manifestations. 4 These observations suggest that the presence of aPLAs alone is not sufficient to promote thrombosis. Most likely, a priming factor of infectious or inflammatory origin is needed. The implication of infection is particularly obvious in catastrophic APS, a rare but fatal subset of APS, which presents with characteristic features comparable with those occurring in septic shock. 5,6 Stimulation of endothelial cells by aPLAs has been shown to be mediated by intracellular pathways dependent on NF-B, 7,8 p38-MAPK, 9,10 myeloid differentiation factor 88, and TNF receptor-associated factor 6. 11 The latter mediates signaling by members of the TLR family. The TLRs are a family of integral membrane proteins that recognize conserved pathogen-associated molecular patterns. These receptors thereby function as the first line of defense against pathogens and are essential factors in the innate immune response. 12 Among the 10 TLRs present in humans, TLR4/MD2 forms homodimers and recognizes lipopolysaccharide (LPS), 13 whereas TLR2 heterodimerizes with TLR1 or TLR6 and recognizes bacterial triacylated or diacylated lipopeptides. 14 TLRs work with accessory proteins, which help in ligand recognition and binding. One of these, CD14, functions as an accessory protein for both TLR4 and TLR2. 13,15,16 We demonstrated previously that TLR2 is required for the activation of mouse embryonic fibroblasts by aPLAs. 17 In contrast, in a mouse thrombosis model, the absence of functional TLR4 reduced the prothrombotic effect of aPLAs. 18 Monocytes constitutively express TLR2, TLR4, and CD14,19,20 whereas endothelial cells express TLR4 and very low levels of TLR2 and CD14. 17,21,22 Expression of TLR2 by human endothelial cells is strongly increased after activation by inflammatory stimuli such as TNF, LPS, or IL-1␤. 23,24 The principal aim of the present work was to investigate the respective role of TLR2 and TLR4 in human cell activation by aPLAs. We used 3 cell types for our studies: monocytes, endothelial cells, and human embryonic kidney 293 (HEK293) cells expressing either TLR2 or TLR4. Cell activation by aPLAs was inhibited by antibodies to TLR2 or CD14, but not by antibodies t...

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mentioning

confidence: 77%

Toll-like receptor 2 mediates the activation of human monocytes and endothelial cells by antiphospholipid antibodies

Satta¹,

Kruithof²,

Fickentscher³

et al. 2011

Blood

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“…Previous case reports and case-control studies have linked ATxA with polymyositis [16], rheumatoid arthritis (RA) [17e19], autoimmune thyroid diseases [20,21], Crohn's disease [22], anti phospholipid syndrome [23], Wegener's granulomatosis [24] and autoimmune bullous diseases [25]. While ATxA have been previously associated with SLE [26], subsequent studies challenged this association [27,28].…”

Section: Introductionmentioning

confidence: 95%

Prevalence of anti-toxoplasma antibodies in patients with autoimmune diseases

Shapira¹,

Agmon‐Levin²,

Selmi³

et al. 2012

Journal of Autoimmunity

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“…Parasites in general are considered to be influential immunomodulators, implicated in allergic and autoimmune diseases (Kivity et al, 2009). We recently noticed that serological evidence of T. gondii, specifically, is elevated in several autoimmune diseases, including systemic sclerosis, antiphospholipid syndrome, inflammatory bowel disease, autoimmune thyroid diseases, cryoglobulinemia, and ANCA-associated vasculitides (Arnson et al, 2009;Lidar et al, 2009aLidar et al, , 2009bShapira et al, 2012;Tozzoli et al, 2008;Zinger et al, 2009). Insinuating a potential link to PBC, it was demonstrated that Toxoplasma genome encodes PDC-E2, which is highly represented and exclusively localized inside the parasite apicoplast (a nonphotosynthetic plastid, which is essential for the parasite viability, carbohydrate and fatty acid metabolism) (Fleige et al, 2007).…”

Section: Discussionmentioning

confidence: 99%