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Complexes between proteinase 3, α 1 ‐antitrypsin and proteinase 3 anti‐neutrophil cytoplasm autoantibodies: a comparison between α 1 ‐antitrypsin PiZ allele carriers and non‐carriers with Wegener's granulomatosis
Author(s) -
Baslund B.,
Szpirt W.,
Eriksson S.,
Elzouki A.N.,
Wiik A.,
Wieslander J.,
Petersen J.
Publication year - 1996
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.1996.2070553.x
Subject(s) - autoantibody , proteinase 3 , medicine , negativity effect , allele , gastroenterology , immunology , population , anti neutrophil cytoplasmic antibody , disease , antibody , vasculitis , biology , psychology , genetics , gene , environmental health , social psychology
To test the hypothesis that anti‐neutrophil cytoplasm autoantibodies (ANCAs) interfere with the functions of proteinase 3 (PR3) (the Wegener autoantigen) and α 1 ‐antitrypsin (α 1 AT), complexes of PR3/α 1 AT and PR3/PR3‐ANCA‐IgG were assayed. Plasma samples were obtained from 44 patients with Wegener's granulomatosis (WG): 34 had active disease (88% ANCA positive) whereas 10 patients were in remission (20% ANCA positive). Plasma samples from 14 of the patients with active disease were also available at the time of remission. The complexes of PR3/α 1 AT and PR3/PR3‐ANCA‐IgG were detected by capture enzyme‐linked immunoassays (ELISAs). α 1 AT deficiency was evaluated by determining PiZ alleles by ELISA. Eight (18%) of the patients were PiZ positive. The frequency of this α 1 ‐antitrypsin phenotype in the Scandinavian population is 4.7% ( P < 0.001). The median PR3/α 1 AT complex level in the PiZ‐positive group with active disease ( n = 5) was similar to the level in the PiZ‐negative group with active disease. During remission the median level for the PR3/α 1 AT complex was significantly higher than in the acute group ( P < 0.001) including both PiZ‐positive and PiZ‐negative patients. No difference between PiZ positivity and PiZ negativity could be found in the remission group. PR3/PR3‐ANCA‐IgG complexes were found in patients with acute disease as well as in patients in remission, in almost equal frequency. This complex was also present in 13/18 ANCA‐negative samples from patients in remission. Finally, purified IgG fractions from WG patients were examined for their capacity to inhibit binding between PR3 and α 1 AT. An effect on the binding between PR3 and α 1 AT by PR3‐ANCA could not be demonstrated. Thus, our results do not support the hypothesis that PR3‐ANCA interferes with the binding between PR3 and α 1 AT. However, the high prevalence of the PiZ alleles among WG patients suggests that an imbalance between proteinases and α 1 AT may be of importance in this disease. The clinical usefulness of both the PR3/α 1 AT and the PR3/PR3‐ANCA‐IgG complexes and the possible influence on ANCA detection need to be examined in prospective longitudinal studies.