Proinflammatory genotype of interleukin-1 and interleukin-1 receptor antagonist is associated with ESRD in proteinase 3-ANCA vasculitis patients.
BACKGROUND
Small-vessel vasculitides are associated with antineutrophil cytoplasmic antibodies (ANCAs). Cytoplasmic ANCAs are targeted mainly against proteinase 3 (PR3), whereas myeloperoxidase (MPO) is the major antigen of perinuclear ANCAs. These relapsing vasculitides show heterogeneous clinical pictures, and disease severity may vary broadly from mild local organ manifestation to acute organ failure (eg, renal failure). We tested whether two cytokine polymorphisms in the interleukin-1beta (IL-1beta) and IL-1 receptor antagonist (IL-1ra) genes, known to determine cytokine secretion, are associated with clinical manifestations and outcome of ANCA-associated vasculitides.


METHODS
Polymerase chain reaction and restriction fragment length polymorphism analyses were performed to determine polymorphisms in the IL-1beta and IL-1ra genes in 79 patients with PR3-ANCA, 30 patients with MPO-ANCA vasculitis, and 196 healthy controls.


RESULTS
The frequency of the so-called proinflammatory genotype, characterized by high secretion of IL-1beta and low secretion of its antagonist IL-1ra, was increased significantly in patients with PR3-ANCA with end-stage renal disease.


CONCLUSIONS
Patients with a renal manifestation of PR3-ANCA vasculitis have an increased risk for developing end-stage renal disease when carrying the proinflammatory IL-1beta/IL-1ra genotype. Anti-inflammatory therapy specifically antagonizing the proinflammatory effect of IL-1beta may be a promising treatment for patients with Wegener's granulomatosis with renal manifestations.
Department of Medical Microbiology, University of Tübingen, Tübingen, Germany. stefan.borgmann@med.uni-tuebingen.de
Stefan
S
Borgmann
Georg
G
Endisch
Ulrich T
UT
Hacker
Bong-Seok
BS
Song
Harald
H
Fricke
D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic; D016022:Case-Control Studies; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics*; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000628:therapy; D008875:Middle Aged; D053146:Myeloblastin; D009195:Peroxidase / Q000276:immunology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D006435:Renal Dialysis; D012697:Serine Endopeptidases / Q000276:immunology; D012795:Sialoglycoproteins / Q000235:genetics*; D014657:Vasculitis / Q000150:complications / Q000235:genetics* / Q000276:immunology
D019268:Antibodies, Antineutrophil Cytoplasmic; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D009195:Peroxidase; D012697:Serine Endopeptidases; D053146:Myeloblastin