High prevalence of autoantibodies to hLAMP-2 in anti-neutrophil cytoplasmic antibody-associated vasculitis.
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.
Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria. renate.kain@meduniwien.ac.at
Renate
R
Kain
Henko
H
Tadema
Eoin F
EF
McKinney
Alexandra
A
Benharkou
Ricarda
R
Brandes
Andrea
A
Peschel
Virginie
V
Hubert
Tjerk
T
Feenstra
Gürkan
G
Sengölge
Coen
C
Stegeman
Peter
P
Heeringa
Paul A
PA
Lyons
Kenneth G C
KG
Smith
Cees
C
Kallenberg
Andrew J
AJ
Rees
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000097:blood* / Q000276:immunology*; D001317:Austria; D001323:Autoantibodies / Q000097:blood*; D015153:Blotting, Western; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins / Q000276:immunology*; D008875:Middle Aged; D053146:Myeloblastin / Q000276:immunology; D009426:Netherlands; D009195:Peroxidase / Q000276:immunology; D015995:Prevalence; D012680:Sensitivity and Specificity; D006113:United Kingdom
D001323:Autoantibodies; C497811:LAMP2 protein, human; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins; D009195:Peroxidase; D053146:Myeloblastin