Are anti-proteinase-3 ANCA a useful marker of granulomatosis with polyangiitis (Wegener's) relapses? Results of a retrospective study on 126 patients

Thai, Lan-Huong; Charles, Pierre; Resche-Rigon, Matthieu; Desseaux, Kristell; Guillevin, Loı̈c

doi:10.1016/j.autrev.2013.11.003

Cited by 74 publications

(65 citation statements)

References 37 publications

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“…An overview of published studies regarding the association between an ANCA rise and disease activity is presented in Table 1. Several studies were excluded from this table either because the predictive value of a rise in ANCA was not investigated, or because treatment changes were based on ANCA titer, because of inclusion of patients with PAN or various other reasons [38,56,61,63,69,[73][74][75][76][77].…”

Section: The Predictive Value Of An Anca Rise For a Relapsementioning

confidence: 99%

Maintaining remission in patients with granulomatosis with polyangiitis or microscopic polyangiitis: the role of ANCA

Kemna¹,

Paassen²,

Damoiseaux³

et al. 2017

Expert Opinion on Orphan Drugs

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Introduction: Granulomatosis with Polyangiitis (GPA; formerly Wegener's) and Microscopic Polyangiitis (MPA) are inflammatory disease entities affecting small to medium vessels. They are characterized by the presence of anti-neutrophil cytoplasmic antibodies (ANCA) and are frequently grouped together with Eosinophilic Granulomatosis with Polyangiitis (EGPA; formerly Churg Strauss Syndrome) under the term ANCA-associated Vasculitis (AAV). Due to effective immunosuppressive therapy that was introduced more than 45 years ago, AAV has become a chronic disease in which relapses occur frequently during maintenance treatment or later on after all immunosuppressive therapy is stopped. Since relapses are associated with morbidity and mortality, early detection and prevention of relapses is of great importance. Areas covered: This review focuses on the potential strategies to guide maintenance therapy in patients with GPA or MPA, with an emphasis on patient classifications and the role of serial ANCA measurements. Expert opinion: Risk factors for relapses, e.g., genetic background of the patient, have been studied during the last three decades. Only few of these risk factors directly influence the management of patients. One potentially important factor that may influence therapeutic decisions in AAV patients is serial measurement of ANCA. Recently, it became clear that serial ANCA measurement is an attractive approach in AAV patients with (a history of) capillaritis, e.g., renal involvement or alveolar haemorrhage, but not in patients with more limited disease. Whether ANCA rises can be used to guide therapy andhence-to prevent relapses has been a great debate during the last three decades. At present, we conclude that small studies do support such an approach but that these findings require further validation in larger randomized clinical trials. ARTICLE HISTORY

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Section: The Predictive Value Of An Anca Rise For a Relapsementioning

confidence: 99%

Maintaining remission in patients with granulomatosis with polyangiitis or microscopic polyangiitis: the role of ANCA

Kemna¹,

Paassen²,

Damoiseaux³

et al. 2017

Expert Opinion on Orphan Drugs

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“…18 The presence of ANCA is not the only factor required for disease reactivation, because many rises are not followed by a relapse. 2,15,19 This suggests that other qualities, such as epitope specificity and the sialylation ratio, may determine the pathogenicity of ANCA. 3,20,21 Otherwise, the association may be stronger when newer-generation ANCA methods are used.…”

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confidence: 99%

“…Serial ANCA measurement is an important factor, but is not the only factor that should be considered during follow-up in patients with AAV. 14,15 In 2006, a meta-analysis on the value of ANCA measurements to predict relapses concluded that no firm conclusions could be drawn because of considerable methodologic heterogeneity in the different studies. 4 By contrast, another metaanalysis based on a more selected subgroup of these studies concluded that serial ANCA measurements have limited use.…”

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confidence: 99%

ANCA as a Predictor of Relapse

Kemna

Damoiseaux

Austen

et al. 2015

Journal of the American Society of Nephrology

184

180

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The value of measuring ANCA during follow-up to predict a relapse is controversial. On the basis of recently obtained pathophysiologic insights, we postulated that measuring ANCA is useful in patients with renal involvement but is less valuable in patients with nonrenal disease. One hundred sixty-six consecutive patients with ANCA-associated vasculitis, positive for either proteinase 3 (PR3)-ANCA or myeloperoxidase (MPO)-ANCA, were included in our study, followed at regular intervals, and tested for PR3-ANCA and MPO-ANCA. In this cohort, 104 patients had renal involvement (72 with PR3-ANCA, 32 with MPO-ANCA) and 62 patients had nonrenal disease (36 with PR3-ANCA, 26 with MPO-ANCA). During an average (6SD) follow-up of 49633 months and 18614 ANCA measurements, 89 ANCA rises and 74 relapses were recorded. ANCA rises correlated with relapses in patients who presented with renal involvement (hazard ratio [HR], 11.09; 95% confidence interval [95% CI], 5.01 to 24.55), but in comparison, associated only weakly with relapses in patients who presented with nonrenal disease (HR, 2.79; 95% CI, 1.30 to 5.98). In conclusion, longitudinal ANCA measurements may be useful in patients with renal involvement but is less valuable in patients with nonrenal disease.

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“…Although called ANCA-associated vasculitis the diagnosis can be made in the absence of a positive ANCA-test. The fact that the great majority of patients with GPA are ANCA-positive and that titers often rise in active disease [9,10] speaks in favor of a pathogenic role of ANCA, as do the genetic association between GPA and PRTN3 (the gene encoding PR3) and SERPINA1 (the gene encoding α1-antitrypsin, the inhibitor PR3) [11].…”

Section: Gpamentioning

confidence: 99%

The clinical presentation and therapy of diseases related to anti-neutrophil cytoplasmic antibodies (ANCA)

Weiner

Segelmark

2016

Autoimmunity Reviews

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Anti-neutrophil cytoplasmic antibodies (ANCA) are a family of autoantibodies that react with proteins predominantly expressed in cytoplasmic granules of polymorphonuclear neutrophil granulocytes (PMNs). ANCA was initially detected using indirect immunofluorescence, allowing for different patterns such as p-ANCA (perinuclear) and c-ANCA (cytoplasmic) to be distinguished. Today it is common to detect the antibodies by immunochemical assays such as ELISA using purified proteins as antigens. The strongest association with ANCA is found in the pauci-immune small vessel vasculitides granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). There is compelling evidence that ANCA contributes to the pathogenesis in these conditions. ANCA also occurs in 30%-40% of patients with eosinophilic granulomatosis with polyangiitis (EGPA) and anti-GBM disease, but is uncommon in other forms of vasculitis. ANCA with different specificities have been described with varying frequencies in diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, inflammatory bowel disease, endocarditis, chronic infections and hematopoietic malignancies. ANCA can also develop as an adverse event during pharmacological treatment. These entities are treated quite differently, with therapies ranging from immunosuppressive agents over antibiotics to simply removing the causative drug. A positive ANCA test thus requires a careful diagnostic work-up. (C) 2016 Elsevier B.V. All tights reserved

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Are anti-proteinase-3 ANCA a useful marker of granulomatosis with polyangiitis (Wegener's) relapses? Results of a retrospective study on 126 patients

Cited by 74 publications

References 37 publications

Maintaining remission in patients with granulomatosis with polyangiitis or microscopic polyangiitis: the role of ANCA

Maintaining remission in patients with granulomatosis with polyangiitis or microscopic polyangiitis: the role of ANCA

ANCA as a Predictor of Relapse

The clinical presentation and therapy of diseases related to anti-neutrophil cytoplasmic antibodies (ANCA)

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