Relevance of classic anti-neutrophil cytoplasmic autoantibody (C-ANCA)-mediated inhibition of proteinase 3-α1-antitrypsin complexation to disease activity in Wegener's granulomatosis

Dolman, Koert M.; Stegeman, Coen A.; Wiel, Bart A. van de; Hack, C. E.; Borne, A. E. G. K. Von Dem; Kallenberg, Cees G. M.; Goldschmeding, Roel

doi:10.1111/j.1365-2249.1993.tb08192.x

Cited by 75 publications

(44 citation statements)

References 22 publications

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“…Similar results were found with an additional sensitivity analysis, thereby strengthening the observation. These changes in the avidity of PR3-ANCA may be linked to the fluctuating presence of the antigen source, as has been suggested in patients with MPO-ANCA [15,19,34]. In addition, the immune system in these patients may be skewed to a proinflammatory state, e.g.…”

Section: Discussionmentioning

confidence: 86%

The avidity of PR3-ANCA in patients with granulomatosis with polyangiitis during follow-up

Kemna

Schlumberger

Paassen

et al. 2016

Clinical and Experimental Immunology

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SummaryThe objective of this study is to investigate whether the avidity of proteinase-3-anti-neutrophil cytoplasmic antibody (PR3-ANCA) changes during follow-up in different subgroups of patients with granulomatosis with polyangiitis (GPA). We selected 10 patients with renal relapsing GPA, 10 patients with renal non-relapsing GPA and 10 patients with non-renal relapsing GPA. In all patients, an ANCA rise occurred during remission. The avidity was measured using a chaotropic approach at the time of an ANCA rise and at the time of a relapse in relapsing patients or timematched during remission in non-relapsing patients. No difference was observed in the avidity at the ANCA rise between renal relapsing patients [26Á2% (15Á5-47Á5)], renal patients without a relapse [39Á6% (21Á2-63Á4)] and non-renal relapsing patients [34Á2% (21Á6-59Á5)]. In renal relapsing patients, the avidity increased significantly from the moment of the ANCA rise to the relapse [difference 6Á4% (0Á0-17Á1), P 5 0Á0273]. The avidity did not increase after an ANCA rise in renal non-relapsing patients [difference 3Á5 (26Á0 to 10Á1), P 5 0Á6250] or in non-renal relapsing patients [difference 23Á1% (28Á0 to 5Á0), P 5 0Á5703]. The avidity of PR3-ANCA increases after an ANCA rise during follow-up in renal relapsing patients, but not after an ANCA rise in renal patients who remain in remission or in non-renal relapsing patients.

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Section: Discussionmentioning

confidence: 86%

The avidity of PR3-ANCA in patients with granulomatosis with polyangiitis during follow-up

Kemna

Schlumberger

Paassen

et al. 2016

Clinical and Experimental Immunology

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“…The association of abnormal phenotypes and PR3-ANCA may occur because a 1 -AT is the major inhibitor of many proteolytic enzymes including PR3 [30,31]. Phenotypes associated with low a 1 -AT plasma levels will result in increased amounts of unbound and uninhibited PR3 that may be immunogenic under certain conditions.…”

Section: Introductionmentioning

confidence: 99%

Clinical associations and characterisation of antineutrophil cytoplasmic antibodies directed against bactericidal/permeability-increasing protein and azurocidin

Cooper¹,

Savige²,

Nassis³

et al. 2000

Rheumatology International

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Bactericidal/permeability-increasing protein (BPI) and azurocidin (AZ) are recently described target antigens of antineutrophil cytoplasmic antibodies (ANCA). In this study, BPI-ANCA were demonstrated most often in patients with ulcerative colitis (36/92, 39%), Crohn's disease (17/66, 26%) and cystic fibrosis (11/14, 79%), but also in patients with rheumatoid arthritis (8/40, 20%), systemic lupus erythematosus (SLE) (111/65, 17%) and mixed connective tissue disease (4/18, 22%). BPI-ANCA were also common in sera containing antinuclear (ANA) (9/43, 21%) or antidouble-stranded (ds) DNA (7/28, 25%) antibodies. There was no increased frequency of abnormal alpha1-antitrypsin (alphal1AT) phenotypes in patients with BPI-ANCA, and BPI-ANCA were not more common in individuals with an abnormal phenotype. The predominant IgG subclasses were IgG1 and IgG3; IgA but not IgM was present. Both IgG and IgA BPI-ANCA were high affinity antibodies, and the affinity of IgG antibodies did not change with time in the sera tested. Four of the five sera (80%) containing BPI-ANCA did not bind to denatured, reduced BPI, suggesting that most BPI-ANCA recognised conformational epitopes. AZ-ANCA were demonstrated in 2/11 patients (18%) with Wegener's granulomatosis, 3/12 (25%) with cystic fibrosis and 3/14 (21%) with chronic active hepatitis. AZ-ANCA were present in 5/25 sera (25%) with ANA, but the levels were only marginally elevated. AZ-ANCA were uncommon in patients with inflammatory bowel and rheumatological diseases, and in sera containing other autoantibodies. Again, there was no association with abnormal alpha1-AT phenotypes. BPI represents a major ANCA target antigen in patients with rheumatological as well as inflammatory bowel disease and cystic fibrosis, but AZ-ANCA are uncommon.

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“…[26] Cytoplasmic ANCA is a serological marker for WG and C-ANCA titers mirror the disease activity, and relapses are often preceded by recurrence or increase in titer of C-ANCA. [27] Rarely, P-ANCA with anti-MPO specificity has been reported in WG. [28], [29] Edgar et al [29] had observed that titration of ANCA by IIF were clinically useful for monitoring disease activity in WG.…”

Section: Discussionmentioning

confidence: 99%

ANCA: Serology in Wegener′s granulomatosis

Pradhan¹,

Badakere²,

Ghosh³

et al. 2005

Indian J Med Sci

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BACKGROUND AND OBJECTIVES Wegener's granulomatosis (WG) is being increasingly diagnosed in India, which exists in two forms, the 'limited Wegener's granulomatosis' (LWG) having upper respiratory tract (URT) and lower respiratory tract (LRT) involvement and the 'classical Wegener 's granulomatosis' (CWG), with the triad of URT, LRT involvement along with kidney involvement. Cytoplasmic ANCA (C-ANCA) or antiProteinase3 (anti-PR3), which is highly diagnostic for WG, rarely perinuclear ANCA (P-ANCA) may exist. Aims To detect anti-neutrophil cytoplasmic antibodies (ANCA) and correlate it with serological, hematological parameters, and the Birmingham Vasculitis Activity Score (BVAS). SETTINGS AND DESIGN Twenty-three clinically and histopathologically proven WG (16 CWG, 7 LWG) were studied. MATERIAL AND METHODS C-ANCA and P-ANCA patterns were identified by immunofluorescence and specificities were confirmed by 'α granule' enzyme linked immunosorbent assay (ELISA), anti-PR3, anti-MPO (myeloperoxidase) and anti-Lactoferrin (anti-LF) by ELISA. RESULTS LRT involvement was seen in 91.3%, URT in 78.3%, and renal manifestations in 69.6% cases. The BVAS in CWG was significantly higher than BVAS in the LWG. Decreased hemoglobin, increased WBC counts, ESR, CRP and Creatinine were seen in CWG as compared to LWG. The C-ANCA was present in 65.2% patients and P-ANCA in 13% cases. Anti-PR3 was seen in 69.6% patients and anti-LF in 17.4% cases. Severity of disease and ANCA was higher in CWG than in LWG. Conclusions Vasculitis syndromes are known to overlap and many go undetected; therefore ANCA testing, along with the clinical and histopathological observations may be helpful in early detection and management of WG cases.

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Relevance of classic anti-neutrophil cytoplasmic autoantibody (C-ANCA)-mediated inhibition of proteinase 3-α1-antitrypsin complexation to disease activity in Wegener's granulomatosis

Cited by 75 publications

References 22 publications

The avidity of PR3-ANCA in patients with granulomatosis with polyangiitis during follow-up

The avidity of PR3-ANCA in patients with granulomatosis with polyangiitis during follow-up

Clinical associations and characterisation of antineutrophil cytoplasmic antibodies directed against bactericidal/permeability-increasing protein and azurocidin

ANCA: Serology in Wegener′s granulomatosis

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