Deregulated platelet-activating factor levels and acetylhydrolase activity in patients with idiopathic IgA nephropathy.
BACKGROUND
Platelet-activating factor (PAF) is a phospholipid mediator with potent inflammatory activities. PAF stimulates IgA synthesis by B cells while IgA aggregates enhance PAF production by neutrophils and mesangial cells. These results led us to investigate blood PAF levels and plasma acetylhydrolase (AHA, the PAF catabolic enzyme) activity in patients with idiopathic IgA nephropathy (IgAN).


METHODS
PAF and AHA levels were investigated using the platelet aggregation assay and degradation of (3)H-labelled PAF, respectively. The genotype of AHA with regard to the G994-->T mutation in exon 9 was assessed by an allele-specific polymerase chain reaction.


RESULTS
Blood PAF levels were significantly (P:=0.003, Mann-Whitney U:-test) elevated in IgAN patients (50.6+/-6.8 pg/ml, n=33) compared with healthy controls (18+/-5 pg/ml, n=18). In contrast, plasma AHA levels were significantly (P:=0.0001, Mann-Whitney U:-test) reduced in patients with IgAN (61+/-2 nmol/ml/min, n=51) compared with healthy controls (78+/-4 nmol/ml/min, n=53). G994-->T transversion in exon 9 of AHA was not found in any of the IgAN patients.


CONCLUSIONS
Elevated circulating levels of PAF in IgAN patients might result from an insufficient AHA probably related to environmental factors rather than genetic ones. The mechanism and the precise role of the PAF/AHA deregulation in IgAN patients remain to be clarified.
Denizot
Y
Y
EP CNRS 118, Faculté de Médecine, 2 rue Dr Marcland, Limoges,
Aupetit
C
C
Bridoux
F
F
Alphonse
J C
JC
Cogné
M
M
Aldigier
J C
JC
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000328:Adult; D001483:Base Sequence / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D005838:Genotype; D005922:Glomerulonephritis, IGA / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010741:Phospholipases A / Q000097:blood* / Q000235:genetics; D010972:Platelet Activating Factor / Q000032:analysis*
D010972:Platelet Activating Factor; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase