Clinical relevance of anti‐PR3 capture ELISA in diagnosing Wegener's granulomatosis

Feng, Zhenru; Liu, Ping; Li, Zhiyan; Bao-huan, Sui

doi:10.1002/jcla.20204

Cited by 9 publications

(3 citation statements)

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“…Since results with patient-derived PR3 Abs generally recapitulated those with the MAbs, showing binding to three-dimensional epitopes at the active site of PR3 and inhibition by α-1-antitrypsin, this would theoretically predict that capture assays for PR3 AuAbs based on these MAbs would not work. Yet, MAb PR3 capture assays have been reported to complement direct coating ELISAs and to have similar or even improved sensitivity compared with these [ 36 , 62 , 63 , 64 , 65 ]. The results presented here indicate that the capture effect of some (PR3) MAbs is partly due to a direct protein–protein interaction between PR3 and the coating MAbs, possibly mediated by the PR3-associated α-defensins, which are known to interact with a variety of different molecules [ 44 , 45 , 46 ].…”

Section: Discussionmentioning

confidence: 99%

Defensin Interactions in Relation to Monoclonal and Disease-Related Proteinase 3 Antibodies Binding at the Catalytic Site

et al. 2023

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Proteinase 3 (PR3) is a neutrophil granulocyte enzyme and an autoantigen found in several forms of vasculitis. Due to the diagnostic and clinical importance of antibodies (Abs) to PR3, it is important to characterize the protein and the nature of its epitopes. Here, we have characterized PR3 monoclonal antibodies (MAbs) and disease-associated Abs and their dependency on the PR3 structure and modifications, especially interactions with α-defensins. Three MAbs (HYB 172-01, 172-04, 172-05), which bind to PR3 in its native and denatured forms and provide the disulphide bridges, were intact. α-1-antitrypsin (AT) binds to purified human neutrophil granulocyte PR3 and inhibits its proteolytic activity, towards a small synthetic peptide substrate and a large protein substrate (casein). AT also inhibited the binding of the three MAbs to PR3, indicating that they bind in a region affected by AT binding. However, the MAbs did not inhibit PR3 proteolytic activity with a small substrate, showing that they bound at the active site without restricting access to the substrate cleft. Patient-derived Abs showed essentially the same characteristics as the MAbs, with important implications for vasculitis diagnostics and pathophysiology. Current findings illustrate that PR3 epitopes depend on the three-dimensional structure of the PR3/defensin complex, and that the epitopes depend to a smaller or larger degree on PR3/defensin associations.

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Section: Discussionmentioning

confidence: 99%

Defensin Interactions in Relation to Monoclonal and Disease-Related Proteinase 3 Antibodies Binding at the Catalytic Site

et al. 2023

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“…Enzyme-linked immunosorbent assay (ELISA) is one of the confirmatory tests for ANCA, which can identify both serum ANCA titers and their target antigens on neutrophils [56]. A combination of IIF and ELISA tests provides up to 92% of sensitivity and 99% of specificity [58]. Although the tests have extremely high sensitivity, ANCA are sometimes undetectable in patients with mild symptoms, especially those who present with granulomatous disease limited to the respiratory tract [59].…”

Section: Anca As a Preliminary Diagnostic Toolmentioning

confidence: 99%

Antineutrophil cytoplasmic antibodies – their role in pathogenesis, diagnosis and treatment monitoring of ANCA-associated vasculitis

Fijołek¹,

Wiatr²

2020

cejoi

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Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) constitutes a group of rare diseases characterized by necrotizing inflammation of small blood vessels and the presence of ANCA. Increasing clinical and experimental evidences support their pathogenic role in AAV, but the exact mechanism is not fully understood. Recently, the important role of neutrophil extracellular traps (NETs) in pathogenesis of AAV is underlined. There is an indication that NETs can be a source for the formation of ANCA. The most common ANCA target antigens are myeloperoxidase (MPO) and proteinase 3 (PR3). Though the mechanism of action of ANCA is still under exploration, ANCA serology is being increasingly used for classification of AAV and revealed as kenner in defining various disease subsets associated with different genetic background, clinical features, treatment response, and prognosis. Controversy exists regarding the utility of serial measurements of ANCA in patients with AAV to monitor treatment and predict disease relapse.

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“…The sensitivity of anti-PR3 classic ELISA and capture ELISA in diagnosing WG was 74% and 88%, respectively whereas specificity was identical (100%). The combination of IIFT with anti-PR3 capture ELISA increased sensitivity for WG patients up to 91.6% which is why it is recommended to apply both tests in parallel [8].…”

mentioning

confidence: 99%

The challenge of Wegener’s granulomatosis after kidney transplantation

Schewior

Dragun

Schaeffner

2009

Transplant International

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Clinical relevance of anti‐PR3 capture ELISA in diagnosing Wegener's granulomatosis

Cited by 9 publications

References 9 publications

Defensin Interactions in Relation to Monoclonal and Disease-Related Proteinase 3 Antibodies Binding at the Catalytic Site

Defensin Interactions in Relation to Monoclonal and Disease-Related Proteinase 3 Antibodies Binding at the Catalytic Site

Antineutrophil cytoplasmic antibodies – their role in pathogenesis, diagnosis and treatment monitoring of ANCA-associated vasculitis

The challenge of Wegener’s granulomatosis after kidney transplantation

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