The target antigens of antineutrophil cytoplasmic antibodies (ANCA) induced by propylthiouracil

Gao, Ying; Chen, Min; Ye, Hua; X, Guo; Zhao, Ming‐Hui; Wang, Haiyan

doi:10.1016/j.intimp.2006.07.033

Cited by 38 publications

(38 citation statements)

References 22 publications

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“…However, Manolova and Dantcheva reoprted that rheumatoid arthritis patients with P-ANCA by IF showing reactivities to major or minor neutrophil antigens exhibited significantly higher inflammatory activity [14]. Furthermore, a recent report by Gao et al suggests that patients with multiple 'ANCA-associated antigens' may be at increased risk of developing overt clinical vasculitis [29]. Clearly, while these antibodies may have no pathological role determined as yet, they may at least be markers of an inflammatory process.…”

Section: Discussionmentioning

confidence: 99%

Antibodies to selected minor target antigens in patients with anti-neutrophil cytoplasmic antibodies (ANCA)

Talor¹,

Stone²,

Stebbing³

et al. 2007

Clinical and Experimental Immunology

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SummaryIn patients with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, indirect immunofluorescence (IF) distinguishes between cytoplasmic (C-ANCA) and perinuclear (P-ANCA) neutrophil staining patterns. In patients with primary systemic vasculitis such as Wegener's granulomatosis, microscopic polyangiitis and Churg-Strauss syndrome, these IF staining patterns correspond broadly with antibodies to the two major antigens: the C-ANCA pattern is associated generally with antibodies to serine protease 3 (PR3) and the P-ANCA pattern with antibodies to myeloperoxidase (MPO). However, some sera positive for ANCA by IF are negative for anti-PR3 and anti-MPO antibodies, suggesting the presence of antibodies to minor antigens of PMN granules. We tested sera from a previously well-defined clinical cohort of patients for antibodies to four possible minor antigens: bactericidal permeability increasing protein, elastase, cathepsin G and lactoferrin. IF-positive (+) sera had significantly higher antibody frequencies to the minor antigens than did the IF-negative (-) sera (P < 0·01). Patients with IF+ PR3 -MPO -sera showed the most varied reactivity to the minor antigens. Among the IF + groups, the IF + PR3 + /MPO -sera showed the lowest reactivity to the minor antigens. Patients with well-defined ANCA specificities, e.g. the PR3-ANCA response associated with Wegener's granulomatosis, are less likely than are other patient subsets to have antibodies to minor antigen targets. Autoantibodies to these minor antigens contribute to the overall pattern of ANCA identified by IF and help to explain why the correlation between IF and enzyme immunoassays show discrepancies. While the pathophysiological significance of antibodies to minor target antigens needs further evaluation, they may be markers of inflammation associated with disease processes.

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Section: Discussionmentioning

confidence: 99%

Antibodies to selected minor target antigens in patients with anti-neutrophil cytoplasmic antibodies (ANCA)

Talor¹,

Stone²,

Stebbing³

et al. 2007

Clinical and Experimental Immunology

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“…The majority of these patients had ANCA directed against MPO, although ANCA that were simultaneously directed against other antigens such as human leukocyte elastase, lactoferrin, and even PR3 were also described (210,211). Even cases of classical WG induced by PTU have been reported (212,213); however, a number of patients showed no clinical signs of vasculitis, despite persistent positive PR3-ANCA titers (211).…”

Section: Pharmacologic Inductionmentioning

confidence: 99%

Hypotheses on the Etiology of Antineutrophil Cytoplasmic Autoantibody–Associated Vasculitis

Wijngaarden¹,

Rijn²,

Hagen³

et al. 2008

Clinical Journal of the American Society of Nephrology

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The first description of what is now known as antineutrophil cytoplasmic autoantibody-associated necrotizing vasculitis appeared more than 140 yr ago. Since then, many aspects of the pathogenic pathway have been elucidated, indicating the involvement of antineutrophil cytoplasmic autoantibodies, but why antineutrophil cytoplasmic autoantibodies are produced in the first place remains unknown. Over the years, many hypotheses have emerged addressing the etiology of antineutrophil cytoplasmic antibody production, but no exclusive factor or set of factors can so far be held responsible. Herein is reviewed the most influential hypotheses regarding the causes of antineutrophil cytoplasmic antibody-associated vasculitis with the aim of placing in an epidemiologic background the different hypotheses that are centered on environmental and genetic influences.Clin J Am Soc Nephrol 3: 237-252, 2008237-252, . doi: 10.2215 A ntineutrophil cytoplasmic autoantibody (ANCA)-associated necrotizing vasculitis was probably first described in 1866 by Kussmaul and Maier (1) as "polyarteritis nodosa." It was not until the early 1930s when the first case of what was later named Wegener's granulomatosis (WG) was described (2). The disease was named after Friedrich Wegener, who described it as an entity in 1939 (3). In 1985, antibodies associated with the disease were detected and later became known as ANCA (4). WG is a systemic autoimmune disease that can cause damage in various organs. Later, microscopic polyangiitis (MPA) was distinguished as a separate ANCA-associated vasculitis. The disease-or its immunosuppressive treatment-can cause high levels of morbidity and death, especially in patients with renal involvement. Animal experiments have shown that ANCA directed against myeloperoxidase (MPO) can cause vasculitis that resembles human vasculitic disease (5,6); however, the cause of ANCA production remains unresolved.Theories have been developed to explain how ANCA could interact with neutrophils, along with monocytes and most probably T lymphocytes, to form the lesions that are characteristic of ANCA-associated vasculitis, such as fibrinoid necrosis and granulomas (7). A recent theory of interest has been postulated by Pendergraft et al. (8), stating that an antibody against the complementary peptide of proteinase-3 (PR3) in an idiotypic/anti-idiotypic network is essential to the development of ANCA and to the development of clinical vasculitis, but why and how these ANCA are produced in the first place remains unanswered. Nonetheless, many hypotheses have been developed about the initiating factor for ANCA production. Many factors, either directly or indirectly, have been considered important in the development of ANCA: Silica exposure (9); genetic predisposition (10); bacterial infection by Staphylococcus aureus (11); viral infection by, for instance, parvovirus B19 (12); and thyroid drugs (13) all have been correlated with and held to contribute to the incidence of ANCA-associated vasculitis. Some of these hypotheses are still th...

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“…1,2 Moreover, this observation appears to be associated with an increased risk of the development of clinical signs. 3 The pathogenesis of PTU-induced AAV is not yet fully understood. PTU decreases thyroid hormone production by inhibiting the enzym thyroid peroxidase.…”

Section: Discussionmentioning

confidence: 99%

“…First, the antigenic specificity of ANCA seems to play a role. Gao and colleagues 3 showed that most patients with clinical overt PTU-induced vasculitis show multiple ANCA reactivities (92.6%) and/or MPO-ANCA positivity (92.6%). In both cases, these antibody profiles were significantly more common in patients with overt vasculitis compared to those without symptoms (multiple reactivities: 92.6 versus 31.6%; MPO-ANCA: 92.6 versus 36.8%).…”

Section: Discussionmentioning

confidence: 99%

“…In both cases, these antibody profiles were significantly more common in patients with overt vasculitis compared to those without symptoms (multiple reactivities: 92.6 versus 31.6%; MPO-ANCA: 92.6 versus 36.8%). 3 Secondly, the immunological characteristics of the MPO-ANCA antibodies might be of particular importance. Both titers as well as avidity of MPO-ANCA were significantly higher in patients with clinical overt PTU-induced vasculitis compared to asymptomatic patients and epitope specificity against MPO-ANCA was different.…”

Section: Discussionmentioning

confidence: 99%

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Propylthiouracil induced ANCA-associated vasculitis in a 14-year-old girl

Schamp¹,

Verfaillie²,

Bonroy³

et al. 2015

Acta Clinica Belgica

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The target antigens of antineutrophil cytoplasmic antibodies (ANCA) induced by propylthiouracil

Cited by 38 publications

References 22 publications

Antibodies to selected minor target antigens in patients with anti-neutrophil cytoplasmic antibodies (ANCA)

Antibodies to selected minor target antigens in patients with anti-neutrophil cytoplasmic antibodies (ANCA)

Hypotheses on the Etiology of Antineutrophil Cytoplasmic Autoantibody–Associated Vasculitis

Propylthiouracil induced ANCA-associated vasculitis in a 14-year-old girl

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