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Novel SNPs in the CD18 gene validate the association with MPO-ANCA + vasculitis

Genes & Immunity volume 2, pages 269–272 (2001)Cite this article

Abstract

Wegener granulomatosis (WG), microscopic polyangiitis (MP), and Churg-Strauss syndrome (CSS) are characterized by the presence of anti-neutrophil cytoplasmic antibodies (ANCA). Anti-myeloperoxidase (MPO)-ANCA are a typical feature of MP and CSS, while anti-proteinase 3 (PRTN3)-ANCA are highly specific for WG. Several reports indicate that ANCA may directly contribute to pathological processes, ie, through an increase of adhesivity between polymorphonuclear (PMN) and endothelial cells (EC). PMN interact and endothelium interact via the adhesion cascade (AC). CD18 is a key molecule of the AC, as CD18 defects abbrogate the adhesion of PMN and cause leukocyte adhesion deficiency, an immunodeficient trait. We have screened the entire coding and regulatory regions of the CD18 gene. Ten single nucleotide polymorphisms (SNP) were identified, four of them showing significant associations with MPO-ANCA+ vasculitis. One of these SNP’s was localized in an alternate transcription initiation site. This polymorphism may influence CD18 gene expression, resulting in dose-dependent increase in adhesion and consecutively facilited degranulation and respiratory burst. In this manner the pro-adherent genotype may predispose to MPO-ANCA+ vasculitis.

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Acknowledgements

Our thanks to Dr Alex Law, BS PhD, MRC Immunochemistry Unit at the Department of Biochemistry, Oxford University, for providing us with CD18 intronic sequences.

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Author notes

  1. S Borgmann

    Present address: Institut für Medizinische Mikrobilogie, Universität Tübingen, Elfriede-Aulhorn-Str. 6, Tübingen, 72076, Germany

  2. H Fricke

    Present address: SmithKline Beecham Pharmaceuticals, Harlow, CM19 5AW, Essex, UK

Authors and Affiliations

  1. Human Molecular Genetics, Ruhr-University Bochum, Germany

    S Meller, P Jagiello, JT Epplen & M Gencik

  2. Medizinische Klinik, Klinikum Innenstadt, University Munich, Germany

    S Borgmann & H Fricke

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  1. S Meller
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  2. P Jagiello
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  3. S Borgmann
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  4. H Fricke
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  5. JT Epplen
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  6. M Gencik
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Correspondence to M Gencik.

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Meller, S., Jagiello, P., Borgmann, S. et al. Novel SNPs in the CD18 gene validate the association with MPO-ANCA + vasculitis . Genes Immun 2, 269–272 (2001). https://doi.org/10.1038/sj.gene.6363781

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