Analysis of anti‐neutrophil cytoplasmic antibodies (ANCA): frequency and specificity in a sample of 191 homozygous (PiZZ) alpha1‐antitrypsin‐deficient subjects

Audrain, Marie; Sesboüé, Richard; Baranger, Thierry; Elliott, Jane; Testa, Angelo; Martín, J. P.; Cm, Lockwood; Esnault, Vincent

doi:10.1093/ndt/16.1.39

Cited by 41 publications

(24 citation statements)

References 35 publications

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“…The possibility of false positive results because of nonspecific binding or rheumatoid factor binding to the monoclonal captured antibody could be easily excluded by using a control plate coated with an unrelated monoclonal antibody of the same isotype as the captured one. Using PR3 capture ELISA, the correlation between ELISA antibody titres and either the IIF results or the disease activity is better than with direct ELISA [30]. The PR3 capture ELISA showed a significantly higher sensitivity in patients with WG with renal involvement compared to cANCA IIF (85% versus 58%) [59].…”

Section: Elisamentioning

confidence: 94%

“…ANCA that are not directed against classical antigens, such as PR3 and MPO, may be found in PiZZ patients, usually free from systemic vasculitis features. It seems that A1T deficiency is not sufficient to induce ANCA vasculitis, being merely a hit-amplifying factor [30].…”

Section: Laboratory Considerations For Setting Clinically Meaningful mentioning

confidence: 99%

“…The deficient PiZZ gene is expressed in 20% of PR3 ANCA-associated vasculitis population versus 4.7% of the whole population. WG clinical disease activity is correlated with the percentage of inhibition of the binding of PR3/A1T complexes by the PR3 ANCA [30].…”

Section: Proteinasementioning

confidence: 99%

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Antineutrophil Cytoplasmic Autoantibodies: How Should the Biologist Manage Them?

Beauvillain

Delneste

Rénier

et al. 2008

Clinic Rev Allerg Immunol

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Antineutrophil cytoplasmic antibodies (ANCA) are directed against enzymes found in the granules of the polymorphonuclear (PMN) leukocytes. They are detected by indirect immunofluorescence microscopy assays on human ethanol fixed neutrophils. Three different fluorescence patterns can be distinguished: a cytoplasmic pattern (cANCA), a perinuclear pattern (pANCA), and an atypical pattern (aANCA). The use of other fixatives, e.g., formalin and methanol, allows differentiation between the pANCA and the antinuclear antibodies. ANCA specificity is determined by solid phase assays (ELISA, immunodot, and multiplex assay). ANCA with high titres and defined specificities (antiproteinase 3 [PR 3] or antimyeloperoxidase [MPO]) are proven to be good serological markers of active primary systemic vasculitis: c/PR 3-ANCA for Wegener's granulomatosis and p/MPO-ANCA for microscopic polyangiitis. The former have higher sensitivity and specificity for Wegener's granulomatosis than the latter for microscopic polyangiitis. ANCA with low titres and unknown specificity have been detected in a wide range of inflammatory and infectious diseases leading to a critical reappraisal of the diagnostic significance of ANCA testing. Physicians must keep in mind the possible occurrence of infectious diseases like subacute endocarditis that could be dramatically worsened by irrelevant immunosuppressive therapy. ANCA findings in certain manifestations, such as the pulmonary-renal syndrome in which massive pulmonary hemorrhage can quickly be life-threatening, warrant ANCA testing as an emergency test for patient care.

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Section: Elisamentioning

confidence: 94%

Section: Laboratory Considerations For Setting Clinically Meaningful mentioning

confidence: 99%

See 1 more Smart Citation

Antineutrophil Cytoplasmic Autoantibodies: How Should the Biologist Manage Them?

Beauvillain

Delneste

Rénier

et al. 2008

Clinic Rev Allerg Immunol

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“…Actually a subpopulation of al-AT deficiency PiZZ patients associated with ANCA-positivesystemic vasculitis has been reported, but it was demonstrated there is no evidence that a PiZZ patient carrying ANCAagainst PR3 or MPOhas a greater risk of developing systemic vasculitis than a PiMM patient carrying ANCA (38). Although the vasculitis associated with al-AT deficiency showed a more widespread and worse prognosis than vasculitis, in PiMMpatients, there was no difference in age at onset or relapse tendency (39).…”

Section: Case Reportmentioning

confidence: 97%

Systemic Vasculitis Associated with .ALPHA.1-antitrypsin Deficiency

et al. 2003

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Wedescribe a rare case of systemic vasculitis associated with al-antitrypsin (al-AT) deficiency. Mutational analysis of the al-AT gene in this patient revealed a homozygousal-AT Mnichinanvariant. al-AT possesses broad-spectrum inhibitory activity against many serine proteases, including humanneutrophil elastase, to help maintaining the crucial balance between proteases and protease inhibitors. The increase in free protease activity in the context of al-AT deficiency may induce exacerbation of the vasculitis. This serious genetic defect severely affects the balance between a protease and a protease inhibitor at the pathological site. (Internal Medicine 42: 619-623, 2003)

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“…Rarok et al [20] have recently become the first investigators to claim a larger mPR3+ subset as a risk factor for relapse in patients with Wegener's granulomatosis. Previously, the PiZ allele, conferring lower · 1 -antitrypsin (A1AT) activity (the major in vivo PR3 inhibitor), has been associated with poorer outcome in patients with ASV although not with the development of ASV per se [22,23]. Rooney et al [24] more recently reported that in vitro neutrophil activation by PR3-ANCA was attenuated in the presence of exogenous A1AT.…”

mentioning

confidence: 99%