Antiendothelial Cells Autoantibodies in Vasculitis-Associated Systemic Diseases

Guilpain, Philippe; Mouthon, Luc

doi:10.1007/s12016-007-8069-3

Cited by 70 publications

(70 citation statements)

References 54 publications

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“…Antiendothelial cell antibodies can be detected in many GPA and MPA patients, but whether they can cause vessel lesions or simply occur as a consequence of vessel damage remains debated (62)(63)(64). The precise molecular targets of these anti-endothelial cell auto-antibodies remain to be better identified.…”

Section: Clinical and Biological Findings Diagnosismentioning

confidence: 99%

Updates in ANCA-associated vasculitis

2016

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Antineutrophil cytoplasm antibody (ANCA)-associated vasculitides are small-vessel vasculitides that include granulomatosis with polyangiitis (formerly Wegener's granulomatosis), microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome). Renal-limited ANCA-associated vasculitides can be considered the fourth entity. Despite their rarity and still unknown cause(s), research pertaining to ANCA-associated vasculitides has been very active over the past decades. The pathogenic role of antimyeloperoxidase ANCA (MPO-ANCA) has been supported using several animal models, but that of antiproteinase 3 ANCA (PR3-ANCA) has not been as strongly demonstrated. Moreover, some MPO-ANCA subsets, which are directed against a few specific MPO epitopes, have recently been found to be better associated with disease activity, but a different method than the one presently used in routine detection is required to detect them. B cells possibly play a major role in the pathogenesis because they produce ANCAs, as well as neutrophil abnormalities and imbalances in different T-cell subtypes [T helper (Th)1, Th2, Th17, regulatory cluster of differentiation (CD)4+ CD25+ forkhead box P3 (FoxP3)+ T cells] and/or cytokine-chemokine networks. The alternative complement pathway is also involved, and its blockade has been shown to prevent renal disease in an MPO-ANCA murine model. Other recent studies suggested strongest genetic associations by ANCA type rather than by clinical diagnosis. The induction treatment for severe granulomatosis with polyangiitis and microscopic polyangiitis is relatively well codified but does not (yet) really differ by precise diagnosis or ANCA type. It comprises glucocorticoids combined with another immunosuppressant, cyclophosphamide or rituximab. The choice between the two immunosuppressants must consider the comorbidities, past exposure to cyclophosphamide for relapsers, plans for pregnancy, and also the cost of rituximab. Once remission is achieved, maintenance strategy following cyclophosphamide-based induction relies on less toxic agents such as azathioprine or methotrexate. The optimal maintenance strategy following rituximab-based induction therapy remains to be determined. Preliminary results on rituximab for maintenance therapy appear promising. Efforts are still under way to determine the optimal duration of maintenance therapy, ideally tailored according to the characteristics of each patient and the previous treatment received.Keywords: Antineutrophil cytoplasmic antibody-associated vasculitis, granulomatosis with polyangiitis (Wegener's granulomatosis), microscopic polyangiitis, Churg-Strauss syndrome (eosinophilic granulomatosis with polyangiitis), cyclophosphamide, rituximab IntroductionAntineutrophil cytoplasm antibody (ANCA)-associated vasculitides are small-vessel vasculitides that include granulomatosis with polyangiitis (GPA; formerly Wegener's granulomatosis), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA; al...

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Section: Clinical and Biological Findings Diagnosismentioning

confidence: 99%

Updates in ANCA-associated vasculitis

2016

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“…18,19 Antibody-mediated endothelial damage also has been described in many diseases, including primary autoimmune vasculitides, 20,21 systemic autoimmune diseases with vascular involvement, 22,23 as well as the early and late stages of atherosclerosis. Among primary autoimmune vasculitides such as Wegener granulamatosis, Kawasaki disease, and Henoch-Schonlein purpura, there is an association between antiendothelial cell antibodies (AECA) and disease status.…”

Section: Introductionmentioning

confidence: 99%

“…Among primary autoimmune vasculitides such as Wegener granulamatosis, Kawasaki disease, and Henoch-Schonlein purpura, there is an association between antiendothelial cell antibodies (AECA) and disease status. [22][23][24][25][26][27] Systemic lupus erythematosus also shows a relationship between AECA prevalence and disease status. 28,29 Indeed, transfer of AECA into rabbits results in systemic lupus erythematosus-like nephritis.…”

Section: Introductionmentioning

confidence: 99%

Evidence for a novel human-specific xeno-auto-antibody response against vascular endothelium

Pham¹,

Gregg²,

Karp³

et al. 2009

Blood

112

138

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Humans are genetically unable to synthesize the common mammalian sialic acid N-glycolylneuraminic acid (Neu5Gc). However, Neu5Gc can be metabolically incorporated and covalently expressed on cultured human cell surfaces. Meanwhile, humans express varying and sometimes high titers of polyclonal anti-Neu5Gc antibodies. Here, a survey of human tissues by immunohistochemistry with both a monospecific chicken anti-Neu5Gc antibody and with affinity-purified human antiNeu5Gc antibodies demonstrates endothelial expression of Neu5Gc, likely originating from Neu5Gc-rich foods like red meats. We hypothesized that the combination of Neu5Gc incorporation and anti-Neu5Gc antibodies can induce endothelial activation. Indeed, the incubation of high-titer human sera with Neu5Gc-fed endothelial cells led to Neu5Gc-dependent antibody binding, complement deposition, endothelial activation, selectin expression, increased cytokine secretion, and monocyte binding. The proinflammatory cytokine tumor necrosis factor-␣ also selectively enhanced human anti-Neu5Gc antibody reactivity. AntiNeu5Gc antibodies affinity-purified from human serum also directed Neu5Gc-dependent complement deposition onto cultured endothelial cells. These data indicate a novel human-specific mechanism in which Neu5Gc-rich foods deliver immunogenic Neu5Gc to the endothelium, giving anti-Neu5Gc antibody-and complement-dependent activation, and potentially contributing to human vascular pathologies. In the case of atherosclerosis, Neu5Gc is present both in endothelium overlying plaques and in subendothelial regions, providing multiple pathways for accelerating inflammation in this disease.

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“…They might contribute to the pathogenesis of systemic vasculitis-associated diseases by activation of endothelial cells, direct cytotoxic effects due to complement-dependent cytotoxicity, indirect cytotoxic effects secondary to antibody-dependent cytotoxicity, induction of coagulation, induction of apoptosis through the binding of phospholipids or heat shock protein, or induction of endothelial cell activation. 1 The targeted antigens of AECA are a large group including matrix proteins and extracellular molecules. 2,3 The AECAs induce the expression of adhesion molecules, E-selectin, intracellular adhesion molecule 1, vascular cell adhesion molecule 1, some interleukins including interleukin 1, interleukin 6, and interleukin 8, and monocyte chemoattractant protein 5,14 .…”

Section: Introductionmentioning

confidence: 99%