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SHR Neuro Cancer Cardio Lipid Metab Microb

Kain, R; Tadema, H; McKinney, EF; Benharkou, A; Brandes, R; Peschel, A; Hubert, V; Feenstra, T; Sengölge, G; Stegeman, C; Heeringa, P; Lyons, PA; Smith, KG; Kallenberg, C; Rees, AJ.
High prevalence of autoantibodies to hLAMP-2 in anti-neutrophil cytoplasmic antibody-associated vasculitis.
J Am Soc Nephrol. 2012; 23(3): 556-566. Doi: 10.1681/ASN.2011090920 [OPEN ACCESS]
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Co-authors Med Uni Graz: Benharkou Alexandra
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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.
Find related publications in this database (using NLM MeSH Indexing): Adult -; Aged -; Aged, 80 and over -; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - blood Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - immunology; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis -; Autoantibodies - blood; Blotting, Western -; Case-Control Studies -; Enzyme-Linked Immunosorbent Assay -; Fluorescent Antibody Technique, Indirect -; Fluorescent Antibody Technique, Indirect -; Humans -; Lysosomal-Associated Membrane Protein 2 -; Lysosome-Associated Membrane Glycoproteins - immunology; Middle Aged -; Myeloblastin - immunology; Myeloblastin -; Peroxidase - immunology; Prevalence -; Sensitivity and Specificity -