ANCAs Are Also Antimonocyte Cytoplasmic Autoantibodies

Jennette, J. Charles; Falk, Ronald J.

doi:10.2215/cjn.11501114

Cited by 14 publications

(12 citation statements)

References 22 publications

(30 reference statements)

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“…Leukocyte surface expression of TF can be driven by antibody-mediated cell activation 12, 18, 19. ANCA bind both neutrophils and monocytes, 38 but ANCA-driven TF expression has not been examined previously in monocytes or inflammatory monocytes. As a proof of concept, we found PR3-ANCA IgG can stimulate release of MPs with TF activity.…”

Section: Discussionmentioning

confidence: 99%

Elevated Microparticle Tissue Factor Activity Differentiates Patients With Venous Thromboembolism in Anti-neutrophil Cytoplasmic Autoantibody Vasculitis

Mendoza

Brant

McDermott

et al. 2019

Kidney International Reports

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Introduction: Venous thromboembolism (VTE) is a life-threatening complication of anti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis whose mechanism remains incompletely elucidated. We tested the hypothesis that elevated microparticle tissue factor activity (MPTFa) or anti-plasminogen antibodies (anti-Plg) may identify patients at risk for VTE. Methods: In this prospective study, patients were enrolled during active disease and followed longitudinally. Twelve patients who experienced a VTE (VTE pos) were compared with patients without VTE (VTE neg , n ¼ 29) and healthy controls (HC, n ¼ 70). MPTFa, anti-Plg, interleukin-6, high-sensitivity C-reactive protein (hs-CRP), Ddimer, serum creatinine, and serum albumin were assessed. Fisher's exact tests and Wilcoxon tests compared categorical and continuous variables, respectively. Cox regression for time to VTE or last follow-up was performed. Results: VTE pos patients had higher MPTFa (peak median ¼ 14.0, interquartile range ¼ 4.3-36.6) than HC (0, 0-3.5) and VTE neg patients (0, 0-1.4). In time-to-event analysis, MPTFa was associated with VTE when measured during both active disease (hazard ratio [HR]; 95% confidence interval [CI]: 1.04; 1.01-1.08) and remission (1.4; 1.11-1.77). Anti-Plg during remission was also associated with VTE (1.17; 1.03-1.33). Each g/dl decrease of serum albumin was associated with a 4-fold increase in VTE risk (4.4; 1.5-12.9). Adjusting for estimated glomerular filtration rate (eGFR), anti-Plg during remission remained significantly associated with VTE. Conclusion: Elevated MPTFa and increased anti-Plg in remission are strong indicators of VTE independent of renal function. Association of anti-Plg during remission with VTE implies hypercoagulability even during disease quiescence. Hypoalbuminemia strongly portends VTE risk, which is a novel finding in ANCA vasculitis. A thrombotic signature would allow improved management of patients to minimize VTE risk and complications of anticoagulation.

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Section: Discussionmentioning

confidence: 99%

Elevated Microparticle Tissue Factor Activity Differentiates Patients With Venous Thromboembolism in Anti-neutrophil Cytoplasmic Autoantibody Vasculitis

Mendoza

Brant

McDermott

et al. 2019

Kidney International Reports

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“…Although many studies have focussed on neutrophils and their interactions with ANCA in the pathogenesis of disease, monocytes may also play a role in mediating AAV. Monocytes express ANCA antigens, and stimulation of monocytes in vitro with ANCA leads to cytokine production and generation of ROS 50 , 51 . Monocytes from patients with AAV have been shown to express higher levels of CD14, the LPS receptor, than monocytes from patients in remission or healthy controls, suggesting an increased cell activation state in patients with AAV 52 .…”

Section: Anca-induced Activation Of Neutrophils and Monocytesmentioning

confidence: 99%

Recent advances in understanding of the pathogenesis of ANCA-associated vasculitis

Prendecki

Pusey

2018

F1000Res

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Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) are rare systemic autoimmune diseases characterised by inflammation of small blood vessels. Recent developments have been made in our understanding of the pathogenesis of these diseases, including the pathogenic role of ANCA, neutrophils and monocytes as mediators of injury, dysregulation of the complement system, and the role of T and B cells. Current treatment strategies for AAV are based on broad immunosuppression, which may have significant side effects. Advances in understanding of the pathogenesis of disease have led to the identification of new therapeutic targets which may lead to treatment protocols with less-toxic side effects. The aim of this review is to summarise current information and recent advances in understanding of the pathogenesis of AAV.

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“…The early presence of these cells suggests that they may be important in the initiation of kidney damage, as they are considered relevant in the promotion of fibrinoid necrosis, cellular crescent development, and for recruiting the T lymphocytes, which, together with macrophages, dominate the later stages of ANCA GN [36]. CD68+ cells are also present in kidney biopsies of AAV patients with established disease, where they localize preferentially to the sites of active glomerular lesions, including crescents, areas of fibrinoid necrosis, peri-glomerular infiltrates and granulomas [33].…”

Section: Anca-associated Glomerulonephritismentioning

confidence: 99%

The role of monocytes in ANCA-associated vasculitides

Brunini

Page

Gallieni

et al. 2016

Autoimmunity Reviews

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The anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) are a heterogeneous group of diseases causing inflammation in small blood vessels and linked by the presence of circulating ANCA specific for proteinase 3 (PR3) or myeloperoxidase (MPO). These antigens are present both in the cytoplasmic granules and on the surface of neutrophils, and the effect of ANCA on neutrophil biology has been extensively studied. In contrast, less attention has been paid to the role of monocytes in AAV. These cells contain PR3 and MPO in lysosomes and can also express them at the cell surface. Monocytes respond to ANCA by producing pro-inflammatory and chemotactic cytokines, reactive-oxygen-species and by up-regulating CD14. Moreover, soluble and cell surface markers of monocyte activation are raised in AAV patients, suggesting an activated phenotype that may persist even during disease remission. The presence of monocyte-derived macrophages and giant cells within damaged renal and vascular tissue in AAV also attests to their role in pathogenesis. In particular, their presence in the tertiary lymphoid organ-like granulomas of AAV patients may generate an environment predisposed to maintaining autoimmunity. Here we discuss the evidence for a pathogenic role of monocytes in AAV, their role in granuloma formation and tissue damage, and their potential to both direct and maintain autoimmunity. ANCA-activation of monocytes may therefore provide an explanation for the relapsing-remitting course of disease and its links with infections. Monocytes may thus represent a promising target for the treatment of this group of life-threatening diseases.

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ANCAs Are Also Antimonocyte Cytoplasmic Autoantibodies

Cited by 14 publications

References 22 publications

Elevated Microparticle Tissue Factor Activity Differentiates Patients With Venous Thromboembolism in Anti-neutrophil Cytoplasmic Autoantibody Vasculitis

Elevated Microparticle Tissue Factor Activity Differentiates Patients With Venous Thromboembolism in Anti-neutrophil Cytoplasmic Autoantibody Vasculitis

Recent advances in understanding of the pathogenesis of ANCA-associated vasculitis

The role of monocytes in ANCA-associated vasculitides

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