PMID- 10361860
OWN - NLM
STAT- MEDLINE
DCOM- 19990803
LR  - 20210518
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 10
IP  - 6
DP  - 1999 Jun
TI  - A large subset of neutrophils expressing membrane proteinase 3 is a risk factor 
      for vasculitis and rheumatoid arthritis.
PG  - 1224-33
AB  - It has been shown previously that proteinase 3 (PR3), a neutrophil intracellular 
      protease that is the main antigen of antineutrophil cytoplasm (ANCA) 
      autoantibodies, is present on the plasma membrane of a subset of freshly isolated 
      neutrophils. This study shows that the size of this subset of membrane 
      PR3-positive (mPR3+) neutrophils is a stable feature of a given individual, most 
      likely genetically controlled. It ranges from 0 to 100% of neutrophils and allows 
      us to define a new polymorphism in the healthy population, with three discrete 
      phenotypes corresponding respectively to less than 20% mPR3 + neutrophils 
      (mPR3low) or to a mean percentage of 47% (mPR3intermediate) and 71.5% (mPR3high) 
      mPR3+ neutrophils. The frequency of the mPR3high phenotype was significantly 
      increased in patients with ANCA-associated vasculitis (85% versus 55% in healthy 
      subjects). The percentage of mPR3+ neutrophils was not affected by disease 
      activity, relapses, or therapy, and did not reflect in vivo cell activation. In 
      addition, mPR3+ phenotypes were normally distributed in cystic fibrosis patients, 
      indicating that infection and/or inflammation per se do not lead to a high 
      percentage of mPR3+ neutrophils. The frequency of the mPR3high phenotype was not 
      related to anti-PR3 autoimmunization, since it was increased in vasculitic 
      patients regardless of the ANCA specificity (anti-PR3, anti-myeloperoxidase, or 
      unknown). Interestingly, the frequency of the mPR3high phenotype was also 
      increased in patients with rheumatoid arthritis. It was normal in type 
      I-diabetes, a T cell-dependent autoimmune disease. It is proposed here that a 
      high proportion of membrane PR3-positive neutrophils could favor the occurrence 
      or the progression of chronic inflammatory diseases.
FAU - Witko-Sarsat, V
AU  - Witko-Sarsat V
AD  - Institut National de la Sante et de la Recherche Medicale U507 and Department of 
      Nephrology, Necker Hospital, Paris, France. witko-sarsat@necker.fr
FAU - Lesavre, P
AU  - Lesavre P
FAU - Lopez, S
AU  - Lopez S
FAU - Bessou, G
AU  - Bessou G
FAU - Hieblot, C
AU  - Hieblot C
FAU - Prum, B
AU  - Prum B
FAU - Noel, L H
AU  - Noel LH
FAU - Guillevin, L
AU  - Guillevin L
FAU - Ravaud, P
AU  - Ravaud P
FAU - Sermet-Gaudelus, I
AU  - Sermet-Gaudelus I
FAU - Timsit, J
AU  - Timsit J
FAU - Grunfeld, J P
AU  - Grunfeld JP
FAU - Halbwachs-Mecarelli, L
AU  - Halbwachs-Mecarelli L
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (Antibodies, Antineutrophil Cytoplasmic)
RN  - EC 3.4.21.- (Serine Endopeptidases)
RN  - EC 3.4.21.76 (Myeloblastin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibodies, Antineutrophil Cytoplasmic/genetics/*metabolism
MH  - Arthritis, Rheumatoid/*genetics/immunology
MH  - Autoimmune Diseases/*genetics/immunology
MH  - Cystic Fibrosis/genetics
MH  - Diabetes Mellitus, Type 1/genetics
MH  - Female
MH  - Flow Cytometry
MH  - Gene Expression
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Myeloblastin
MH  - Neutrophils/*enzymology/immunology
MH  - Pedigree
MH  - Phenotype
MH  - Reference Values
MH  - Risk Factors
MH  - Sensitivity and Specificity
MH  - Serine Endopeptidases/*genetics/*metabolism
MH  - Vasculitis/*genetics/immunology
EDAT- 1999/06/11 00:00
MHDA- 1999/06/11 00:01
CRDT- 1999/06/11 00:00
PHST- 1999/06/11 00:00 [pubmed]
PHST- 1999/06/11 00:01 [medline]
PHST- 1999/06/11 00:00 [entrez]
AID - 10.1681/ASN.V1061224 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 1999 Jun;10(6):1224-33. doi: 10.1681/ASN.V1061224.