High prevalence of autoantibodies to hLAMP-2 in anti-neutrophil cytoplasmic antibody-associated vasculitis.

Abstract

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 ldlD 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.

• Authors: Renate Kain, Henko Tadema, Eoin F McKinney, Alexandra Benharkou, Ricarda Brandes, Andrea Peschel, Virginie Hubert, Tjerk Feenstra, Gürkan Sengölge, Coen Stegeman, Peter Heeringa, Paul A Lyons, Kenneth G C Smith, Cees Kallenberg, Andrew J Rees
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 23 Issue 3 Pg. 556-66 (Mar 2012) ISSN: 1533-3450 [Electronic] United States
• PMID: 22323643 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• LAMP2 protein, human
• Lysosomal-Associated Membrane Protein 2
• Lysosome-Associated Membrane Glycoproteins
• Peroxidase
• Myeloblastin

Topics

• Adult
• Aged
• Aged, 80 and over
• Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis (blood, immunology)
• Austria
• Autoantibodies (blood)
• Blotting, Western
• Case-Control Studies
• Enzyme-Linked Immunosorbent Assay
• Fluorescent Antibody Technique, Indirect
• Humans
• Lysosomal-Associated Membrane Protein 2
• Lysosome-Associated Membrane Glycoproteins (immunology)
• Middle Aged
• Myeloblastin (immunology)
• Netherlands
• Peroxidase (immunology)
• Prevalence
• Sensitivity and Specificity
• United Kingdom