Antineutrophil cytoplasmic antibodies to proteinase 3 in Wegener's granulomatosis: Epitope analysis using synthetic peptides

被引:37
作者
van der Geld, YM
Simpelaar, A
van der Zee, R
Tervaert, JWC
Stegeman, CA
Limburg, PC
Kallenberg, CGM
机构
[1] Univ Groningen Hosp, Dept Internal Med, NL-9173 GZ Groningen, Netherlands
[2] Univ Utrecht, Inst Infect Dis & Immunol, Utrecht, Netherlands
关键词
ANCA; inflammation; necrotizing crescentic glomerulonephritis; serine proteinase; linear epitopes on PR3;
D O I
10.1046/j.1523-1755.2001.00475.x
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Background. Antineutrophil cytoplasmic antibodies (ANCA) to proteinase 3 (PR3) are strongly associated with Wegener's granulomatosis (WG) and are thought to be involved in its pathogenesis. Levels of PR3-ANCA do not always correspond to clinical disease activity nor to functional effects of these antibodies in vitro, suggesting differences in epitope specificity. To define relevant epitopes for PR3-ANCA, sera of WG patients were analyzed on their reactivity to linear peptides of PR3. Methods. Fifty linear peptides of 15 amino acids in length with an overlap of 10 aa spanning the entire PR3 sequence were synthesized. Sera of 27 WG patients with active disease and 27 age- and sex-matched healthy controls, eight anti-PR3 monoclonal antibodies (mAbs), and a rabbit anti-PR3 serum were tested by enzyme-linked immunosorbent assay for reactivity to PR3 peptides. Results. Rabbit anti-PR3 serum recognized three distinct peptide areas, whereas none of the anti-PR3 mAbs bound PR3 peptides. Sera of both WG patients and healthy controls recognized a restricted number of PR3 peptides. Four of these peptide areas were recognized significantly more strongly by WG sera than by control sera. Sera drawn at the initial presentation of WG mainly recognized these peptides. Two of the recognized peptide areas were located near the active center of PR3. Conclusion. A restricted number of epitope areas of PR3 are recognized both by WG patient sera and control sera. Four peptide areas were bound stronger by sera of WG patients at initial presentation than by healthy controls.
引用
收藏
页码:147 / 159
页数:13
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