Specificity of anti-neutrophil cytoplasmic autoantibodies for proteinase 3 [letter; comment]

Jennette, J. Charles; Hoidal, JR; Rj, Falk

doi:10.1182/blood.v75.11.2263.2263

Cited by 144 publications

(52 citation statements)

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“…A few P-ANCA also react with other neutrophil constituents, such as elastase and lactoferrin [5,18]. Most C-ANCA sera are specific for PR3 [5][6][7][8][9]. Immunochemical assays, such as ELISA, that use purified neutrophil antigens are more definitive than IFA for detecting ANCA with specificity for particular antigens.…”

Section: Discussionmentioning

confidence: 99%

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Frequency of anti-bactericidal/permeability-increasing protein (BPI) and anti-azurocidin in patients with renal disease

Jia

Tuttle

Falk

et al. 1996

Clinical and Experimental Immunology

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SUMMARYThe major subtypes of anti-neutrophil cytoplasmic antibodies (ANCA) detected by indirect immunofluorescence assay (IFA) are P-ANCA and C-ANCA. In patients with vasculitis, myeloperoxidase (MPO) is the major P-ANCA antigen and proteinase 3 (PR3) is the major C-ANCA antigen. BPI and azurocidin, which are also called 57-kD cationic antimicrobial protein (CAP 57) and 37-kD cationic antimicrobial protein (CAP 37), respectively, have been proposed as less frequent target antigens for C-ANCA and P-ANCA. In patients with renal disease, we determined the frequency of antibodies against BPI and azurocidin. By IFA on alcohol-fixed neutrophils, monoclonal and polyclonal anti-BPI antibodies produced a C-ANCA pattern, whereas rabbit anti-azurocidin antibody produced a P-ANCA pattern. By ELISA, sera from 229 P-ANCA-positive patients, 99 C-ANCA-positive patients and 48 ANCA-negative (by IFA) patients with renal biopsies were tested for reactivity with recombinant human BPI and purified human azurocidin. Of these sera, 17 . 5% of P-ANCA, 30 . 3% of C-ANCA and 20 . 8% of IFA-ANCA-negative sera were positive for anti-BPI; and 8 . 3% of P-ANCA, 3 . 0% of C-ANCA and 8 . 3% of IFA-ANCA-negative sera were positive for anti-azurocidin. There was no statistical difference in frequency of anti-BPI between pauci-immune necrotizing and crescentic glomerulonephritis (NCGN) and other glomerular disease (OGD), and there was a lower frequency of antiazurocidin in NCGN samples than in OGD samples. By Western blot, anti-BPI-positive sera reacted with a 57-kD BPI band and anti-azurocidin-positive sera with a 29-kD azurocidin band. In conclusion, there is a low frequency of anti-BPI and anti-azurocidin antibodies in ANCA-positive patient sera; however, this does not correlate with NCGN, which is a marker for ANCA-associated small vessel vasculitis, and a similar positivity is found in IFA-ANCA-negative patients with renal disease. Therefore, serologic detection of anti-BPI and anti-azurocidin is not diagnostically specific in patients with renal disease.

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Section: Discussionmentioning

confidence: 99%

“…In patients with vasculitis, P-ANCA most often have specificity for myeloperoxidase (MPO) [3][4][5], although minor specificities, such as for elastase [5], have been described. The major specificity for C-ANCA is proteinase 3 (PR3) [5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Frequency of anti-bactericidal/permeability-increasing protein (BPI) and anti-azurocidin in patients with renal disease

Jia

Tuttle

Falk

et al. 1996

Clinical and Experimental Immunology

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“…PR3 can degrade a variety of extracellular matrix proteins and other proteins ( Table 2). Perhaps most importantly, PR3 is the antigen recognized by cytoplasmic type anti-neutrophil cytoplasmic autoantibodies (c-ANCA) in patients with Wegener's granulomatosis, which is characterized by a neutrophilic vasculitis [19,20]. PR3 may contribute to the pathogenesis of this disease by its presence on the surface of neutrophils that are activated in response to the binding of ANCA to membrane-bound PR3 [21,22].…”

Section: Human Leukocyte Elastase (Hle) Hle Is Glycoprotein Consist-mentioning

confidence: 99%

The cell biology of leukocyte-mediated proteolysis

Owen

Campbell

1999

Journal of Leukocyte Biology

386

399

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Leukocyte-derived proteinases have the capacity to degrade every component of the extracellular matrix, and thereby play fundamental roles in physiological processes. However, if the activity of these proteinases is uncontrolled or dysregulated, they have the capacity to contribute to tissue injury that potentially affects every organ in the body. Although there is a substantial literature on structure and activity of these proteinases when they are free in solution, until recently there has been little information about the cell biology of proteinases and their inhibitors. Recent studies, however, have identified several mechanisms by which inflammatory cells can degrade extracellular proteins in a milieu that contains high-affinity proteinase inhibitors. J. Leukoc. Biol. 65: 137-150; 1999.

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“…ANCA are serological markers for a range of primary vasculitic diseases, such as Wegener's granulomatosis (WG) and microscopic polyangiitis (MP) [1,2], They can be identified using indirect immunofluorescence (IIF) techniques, by overlaying serum from a patient with suspected vasculitis on to alcoholfixed human polymorphonuclear leucocytes (PMN). This procedure produces two staining patterns: a cytoplasmic pattern (C-ANCA) and a perinuclear pattern (P-ANCA), Proteinase 3 (PR3) and myeloperoxidase (MPO) are the major C-ANCA [3][4][5][6] and P-ANCA [7] antigens, respectively, although other neutrophil granule constituents such as elastase [3,[8][9][10], cathepsin G [9,10], lactoferrin [10,11], and lysozyme [12] have also been associated, more rarely, as autoantigens in vasculitis. In our study we identified a substantial number of serum samples, which produce IIF of either C or P-ANCA type, but did not show specificity for any of these antigens.…”

Section: Introductionmentioning

confidence: 99%

Bactericidal/permeability-increasing protein (BPI) is an important antigen for anti-neutrophil cytoplasmic autoantibodies (ANCA) in vasculitis

Zhao

Jones

Lockwood

1995

Clinical and Experimental Immunology

143

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SUMMARYIndirect immunofluorescence (IIF) techniques have shown that ANCA are useful serological markers for some small vessel vasculitides, and ELISA assays, using purified molecules as solidphase ligand, have helped to identify proteinase 3 (PR3) and myeloperoxidase (MPO) as two of the major ANCA antigens. There remain a substantial number of serum samples, which are positive by IIF, yet recognize neither PR3 nor MPO (double-negative samples). We found, by Western blot analysis of soluble neutrophil granule proteins, that certain ofthese double-negative samples recognized a 55-kD doublet of which the first eight residues shared N-terminal amino acid sequence homology with BPI, a potent antibiotic towards Gram-negative bacteria. We developed a simple, quick and robust two-step immunobiochemical method to purify BPI. This was then employed to detect anti-BPI autoantibodies by ELISA and Western blot analysis. We tested 100 double-negative samples and 400 consecutive new samples sent for routine ANCA testing in the anti-BPI ELISA. We found that 45 of the 100 double-negative and 44 of the 400 new routine samples recognized BPI. By Western blot analysis 20/20 positive anti-BPI samples blotted the 55-kD protein. Inhibition assays confirmed the specificity of binding. Review of the 89 anti-BPI-positive patients showed a male dominance (M: F ratio 55:34), a mean age of 60 4 years and clinical diagnoses ranging from organ limited vasculitis to widespread systemic vasculitis.

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Specificity of anti-neutrophil cytoplasmic autoantibodies for proteinase 3 [letter; comment]

Cited by 144 publications

References 0 publications

Frequency of anti-bactericidal/permeability-increasing protein (BPI) and anti-azurocidin in patients with renal disease

Frequency of anti-bactericidal/permeability-increasing protein (BPI) and anti-azurocidin in patients with renal disease

The cell biology of leukocyte-mediated proteolysis

Bactericidal/permeability-increasing protein (BPI) is an important antigen for anti-neutrophil cytoplasmic autoantibodies (ANCA) in vasculitis

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