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High Prevalence of Autoantibodies to hLAMP-2 in Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Kain, R., Tadema, H., McKinney, E. F., Benharkou, A., Brandes, R., Peschel, A., Hubert, V., Feenstra, T., Sengoelge, G., Stegeman, C., Heeringa, P., Lyons, P. A., Smith, K. G. C., Kallenberg, C. & Rees, A. J., Mar-2012, In : Journal of the American Society of Nephrology. 23, 3, p. 556-566 11 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Renate Kain
  • Henko Tadema
  • Eoin F. McKinney
  • Alexandra Benharkou
  • Ricarda Brandes
  • Andrea Peschel
  • Virginie Hubert
  • Tjerk Feenstra
  • Guerkan Sengoelge
  • Coen Stegeman
  • Peter Heeringa
  • Paul A. Lyons
  • Kenneth G. C. Smith
  • Cees Kallenberg
  • Andrew J. Rees

The involvement of autoantibodies to human lysosome-associated membrane protein-2 (hLAMP-2) in anti neutrophil cytoplasmic antibody (ANCA) associated vasculitis is controversial because of the absence of confirmatory data subsequent to the initial reports of their high prevalence in this disease. We characterized three assays for anti-hLAMP-2 antibodies: ELISA and Western blotting assays using unglycosylated recombinant hLAMP-2 expressed in Escherichia coli, and an indirect immunofluorescence assay using stably transfected IdID cells that expressed glycosylated full-length hLAMP-2 on the plasma membrane. The assays detected autoantibodies to hLAMP-2 in human sera reproducibly and with comparable sensitivity and the assays gave the same results in 80.5% of the test panel of 40 selected positive and negative sera. In untreated patients at presentation, the frequencies of autoantibodies to LAMP-2 were 89%, 91%, and 80%, respectively, among three groups of patients with ANCA-associated vasculitis from Vienna, Austria (n=19); Groningen, the Netherlands (n=50) and Cambridge, United Kingdom (n=53). Prevalence of LAMP-2 autoantibodies was similar in both those with myeloperoxidase-ANCA and proteinase 3-ANCA. Furthermore, we detected LAMP-2 autoantibodies in two ANCA-negative patients. LAMP-2 autoantibodies rapidly became undetectable after the initiation of immunosuppressive treatment and frequently became detectable again during clinical relapse. We conclude that when robust assays are used, circulating autoantibodies to hLAMP-2 can be detected in most European patients with ANCA-associated vasculitis. Large-scale prospective studies are now needed to determine whether they are pathogenic or merely an epiphenomenon.

Original languageEnglish
Pages (from-to)556-566
Number of pages11
JournalJournal of the American Society of Nephrology
Volume23
Issue number3
Publication statusPublished - Mar-2012

    Keywords

  • CRESCENTIC GLOMERULONEPHRITIS, ENDOTHELIAL-CELLS, MEMBRANE-PROTEIN, GRANULOCYTES, H-LAMP-2, RECEPTOR, MICE

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