Blog entry by Arif Khwaja

Anyone in the world

Perhaps one of the more interesting breakthroughs in ANCA associated disease over the last few years has been the finding that anti-lysosome associated membrane protein 2 (LAMP2) antibodies were found in patients with ANCA disease. Anti-LAMP2 antibodies could induce a crescentic GN when injected into rats and like ANCA could activate neutrophils. Furthermore it was postulated that molecular mimicry between a LAMP 2 epitope and the bacterial adhesion protein FimH ( expressed on gram negative bacteria) was the mechanism behind LAMP2 autoantibody production. Again rats immunised with FimH developed a crescentic GN and anti-LAMP2 antibodies - i.e. infection with gram negative bacteria could trigger auto-antibody production of anti-LAMP2 which in turn can induce a crescentic GN.

2 conflicting reports in this months JASN suggest further work is needed to test whether the story pans out as neatly as suggested. Roth and colleagues in found the prevalence of anti-LAMP 2 antibodies to be around only 20% in a cross-sectional cohort from North Carolina and a similar prevalence in a second cohort from Boston. Furthermore they were unable to replicate earlier work demonstrating that injection of anti-LAMP2 antibodies induced a crescentic GN in rats.

In contrast Kain and colleagues analyses samples from three European centres - Cambridge, Vienna and Groningen and found anti-LAMP2 antibodies in 81% of patients though antibody levels quickly disappeared after treatment.

A number of explanations have been postulated to explain these discordant results including methodological differences in the assay used to identify anti-LAMP2 in the two groups and the fact that 2 different patient populations were being studied. Its important to point out that the US data analysed cross-sectional samples and so many of the patients may have been in complete or partial remission. In contrast Kain and colleagues were able to analyse sera from untreated patients at presentation which may explain the higher prevalence in their study. Furthermore they were able to demonstrate that antibody levels appeared to relate to disease activity.

Clearly methodological issues surrounding the assay will be key to resolving these conflicting data and analyses from further centres will be required to ascertain with anti-LAMP2 antibodies will be a useful biomarker if disease in these patients and to clarify the role of infection as an initiating factor for the disease.

Anti–LAMP-2 Antibodies Are Not Prevalent in Patients With Antineutrophil Cytoplasmic Autoantibody Glomerulonephritis

 

 

 

 

 

 

 

 

 

 


Anti–LAMP-2 Autoantibodies in ANCA-Associated Pauci-Immune Glomerulonephritis

 

High prevalence of autoantibodies to hLAMP-2 in anti–neutrophil cytoplasmic antibody–associated vasculitisJ Am Soc Nephrol 23xxxxxx2012

 

 

 

 

  • Aleeza J. Roth*
    1. Kain R
    2. Tadema H
    3. McKinney EF
    4. Benharkou A
    5. Brandes R
    6. Peschel A
    7. Hubert V,
    8. Feenstra T
    9. Sengoelge G
    10. Stegeman C
    11. Heeringa P
    12. Lyons PA
    13. Smith KG,
    14. Kallenberg C
    15. Rees A
[ Modified: Thursday, 1 January 1970, 1:00 AM ]