What is the evidence for antibodies to LAMP-2 in the pathogenesis of ANCA associated small vessel vasculitis?

Abstract

Purpose of review: This review critically analyses the data implicating antibodies to lysosome associated membrane protein-2 (hLAMP-2) in ANCA-associated vasculitis (AAV). It addresses recent controversies over prevalence of anti-hLAMP-2 antibodies as well as their potential for diagnosis and monitoring disease activity.

Recent findings: Anti-hLAMP-2 antibodies were first described in the 1990s and have become the focus of intense clinical interest in the past 4 years. This followed the demonstration of their very high prevalence in untreated patients presenting with AAV but absence when patients were in remission. The data also demonstrated molecular mimicry between hLAMP-2 and the bacterial protein FimH. The same group later confirmed the original findings and showed the anti-hLAMP-2 autoantibodies have different kinetics to those recognising myeloperoxidase and proteinase-3 and are less likely to be detectable when the disease is in remission. By contrast, a different group reported a lower prevalence of anti-hLAMP-2 antibodies in AAV and questioned their relevance to pathogenesis. Critical analysis of these studies suggests that the differences are largely attributable to selection criteria of the AAV patients studied and the assays used.

Summary: Anti-hLAMP-2 antibodies are frequently found in AAV but attempts to define their consequences have been frustrated by lack of generally available assays for them.