PMID- 10594572
OWN - NLM
STAT- MEDLINE
DCOM- 20000113
LR  - 20190513
IS  - 0009-9104 (Print)
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Linking)
VI  - 118
IP  - 3
DP  - 1999 Dec
TI  - Characterization of monoclonal antibodies to proteinase 3 (PR3) as candidate 
      tools for epitope mapping of human anti-PR3 autoantibodies.
PG  - 487-96
AB  - Anti-neutrophil cytoplasmic antibodies directed against PR3 (PR3-ANCA) in 
      patients with Wegener's granulomatosis are supposedly involved in the 
      pathophysiology of this disease as different functional characteristics of the 
      autoantibodies correlate with disease activity. However, little is known about 
      the epitopes of PR3 that are recognized by PR3-ANCA and how epitope specificity 
      may relate to functional characteristics of PR3-ANCA. As candidate tools for 
      epitope mapping we studied 13 anti-PR3 MoAbs, including nine widely used and four 
      newly raised MoAbs, for their mutual binding characteristics to PR3 using 
      biosensor technology. Antigen specificity was confirmed by indirect 
      immunofluorescence, immunoblotting, FACS analysis and antigen-specific ELISA. 
      Competition between anti-PR3 MoAbs in binding to PR3 was investigated in a 
      capture system set up in a BIAcore. In this system grouping of 12 of the 13 
      anti-PR3 MoAbs based on their mutual recognition patterns was achieved. Four 
      MoAbs, from different research groups, namely 12.8, PR3G-2, 6A6 and Hz1F12, 
      recognized comparable epitopes (group 1). Group 2 MoAbs including PR3G-4 and 
      PR3G-6 bound to overlapping regions on PR3. The MoAbs PR3G-3, 4A5 and WGM2 
      recognized similar epitopes as they inhibited binding of each other (group 3). 
      The fourth group of related MoAbs consisted of MC-PR3-2, 4A3 and WGM3. Because of 
      its binding characteristics MoAb WGM1 could not be grouped. These results 
      demonstrate that eight well-established anti-PR3 MoAbs produced by different 
      research groups and four newly produced anti-PR3 MoAbs recognize four separate 
      epitope areas on PR3, including one area detected with newly raised MoAbs only.
FAU - Van Der Geld, Y M
AU  - Van Der Geld YM
AD  - Department of Clinical Immunology, University Hospital Groningen, The 
      Netherlands. Y.M.van.der.geld@med.rug.nl
FAU - Limburg, P C
AU  - Limburg PC
FAU - Kallenberg, C G
AU  - Kallenberg CG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (Antibodies, Antineutrophil Cytoplasmic)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Autoantibodies)
RN  - 0 (Autoantigens)
RN  - 0 (Epitopes)
RN  - EC 3.4.21.- (Serine Endopeptidases)
RN  - EC 3.4.21.76 (Myeloblastin)
SB  - IM
MH  - Antibodies, Antineutrophil Cytoplasmic/metabolism
MH  - Antibodies, Monoclonal/*chemistry/metabolism
MH  - Antibody Specificity/immunology
MH  - Autoantibodies/*metabolism
MH  - Autoantigens/*immunology
MH  - Binding, Competitive/immunology
MH  - Biosensing Techniques
MH  - Enzyme-Linked Immunosorbent Assay
MH  - *Epitope Mapping
MH  - Epitopes/metabolism
MH  - Flow Cytometry
MH  - Fluorescent Antibody Technique, Indirect
MH  - Granulomatosis with Polyangiitis/immunology
MH  - Humans
MH  - Immunoblotting
MH  - Myeloblastin
MH  - Serine Endopeptidases/*immunology
PMC - PMC1905445
EDAT- 1999/12/14 00:00
MHDA- 1999/12/14 00:01
PMCR- 2000/12/01
CRDT- 1999/12/14 00:00
PHST- 1999/12/14 00:00 [pubmed]
PHST- 1999/12/14 00:01 [medline]
PHST- 1999/12/14 00:00 [entrez]
PHST- 2000/12/01 00:00 [pmc-release]
AID - cei1079 [pii]
AID - 10.1046/j.1365-2249.1999.01079.x [doi]
PST - ppublish
SO  - Clin Exp Immunol. 1999 Dec;118(3):487-96. doi: 10.1046/j.1365-2249.1999.01079.x.