Peschel, A., Basu, N. , Benharkou, A., Brandes, R., Brown, M., Dieckmann, R., Rees, A. J. and Kain, R. (2014) Autoantibodies to hLAMP-2 in ANCA-Negative pauci-immune focal necrotizing GN. Journal of the American Society of Nephrology, 25(3), pp. 455-463. (doi: 10.1681/ASN.2013030320) (PMID:24203998) (PMCID:PMC3935581)
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Abstract
Pauci-immune focal necrotizing GN (piFNGN) is usually associated with ANCAs that are thought to be pathogenic. However, 10%–15% of patients are ANCA negative and the cause of their injury is unknown. We previously reported a high frequency of autoantibodies to human lysosome-associated membrane protein-2 (hLAMP-2) in ANCA-associated piFNGN, and have now investigated whether the same is true in ANCA-negative patients. Of 11 patients, 8 (73%) had anti–hLAMP-2 antibodies detected by ELISA and confirmed by immunoblotting and indirect immunofluorescence. The autoantibodies from all 8 patients bound to native LAMP-2 purified from human glomeruli and recombinant hLAMP-2 expressed in ldlD cells, both with molecular masses of 110 kD. However, in contrast to anti–LAMP-2 antibodies from ANCA-positive patients, these antibodies from ANCA-negative patients failed to bind the more complexly glycosylated native neutrophil hLAMP-2 (190 kD). Treatment with the deglycosylating enzyme, endo-b-galactosidase, reduced the mass of neutrophil hLAMP-2 to 110 kD and enabled autoantibody binding. Similarly, pretreating neutrophils with endo-b-galactosidase or neuraminidase converted ANCA assay results from negative to positive. Finally, IgG from LAMP-2-positive ANCAnegative patients bound specifically to normal human kidney sections and to human glomerular endothelial cells in culture. In conclusion, in patients with ANCA-negative piFNGN, we have identified autoantibodies to hLAMP-2 that bind native glomerular but not neutrophil hLAMP-2, suggesting a role in pathogenesis.
| Item Type: | Articles |
|---|---|
| Additional Information: | The research leading to these results received funding from the European Union Seventh Framework Programme (FP7/2007- 2013 Grant 261382) and was supported by the Vienna Science and Technology Fund (Project LS09-075). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Basu, Professor Neil |
| Authors: | Peschel, A., Basu, N., Benharkou, A., Brandes, R., Brown, M., Dieckmann, R., Rees, A. J., and Kain, R. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Journal of the American Society of Nephrology |
| Publisher: | American Society of Nephrology |
| ISSN: | 1046-6673 |
| ISSN (Online): | 1533-3450 |
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