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Autoantibodies targeting glomerular annexin A2 identify patients with proliferative lupus nephritis
Author(s) -
Caster Dawn J.,
Korte Erik A.,
Merchant Michael L.,
Klein Jon B.,
Wilkey Daniel W.,
Rovin Brad H.,
Birmingham Dan J.,
Harley John B.,
Cobb Beth L.,
Namjou Bahram,
McLeish Kenneth R.,
Powell David W.
Publication year - 2015
Publication title -
proteomics – clinical applications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.948
H-Index - 54
eISSN - 1862-8354
pISSN - 1862-8346
DOI - 10.1002/prca.201400175
Subject(s) - lupus nephritis , autoantibody , annexin a2 , podocyte , antibody , antigen , immunology , nephritis , glomerulonephritis , medicine , immune system , annexin , kidney , biology , pathology , disease , proteinuria , flow cytometry
Purpose Patients with systemic lupus erythematosus (SLE) frequently develop lupus nephritis (LN), a complication frequently leading to end stage kidney disease. Immune complex deposition in the glomerulus is central to the development of LN. Using a targeted proteomic approach, we tested the hypothesis that autoantibodies targeting glomerular antigens contribute to the development of LN. Experimental design Human podocyte and glomerular proteins were separated by SDS‐PAGE and immunoblotted with sera from SLE patients with and without LN. The regions of those gels corresponding to reactive bands observed with sera from LN patients were analyzed using LC‐MS/MS. Results LN reactive bands were seen at approximately 50 kDa in podocyte extracts and between 36 and 50 kDa in glomerular extracts. Those bands were analyzed by LC‐MS/MS and 102 overlapping proteins were identified. Bioinformatic analysis determined that 36 of those proteins were membrane associated, including a protein previously suggested to contribute to glomerulonephritis and LN, annexin A2. By ELISA, patients with proliferative LN demonstrated significantly increased antibodies against annexin A2. Conclusion and clinical relevance Proteomic approaches identified multiple candidate antigens for autoantibodies in patients with LN. Serum antibodies against annexin A2 were significantly elevated in subjects with proliferative LN, validating those antibodies as potential biomarkers.