Proteomics

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Minor Antigens in Membranous Nephropathy Identified by Mass Spectrometry


ABSTRACT: Background: Multiple autoantigens have been identified in membranous nephropathy (MN) by tissue-based proteomics. However, the antigenic targets of disease are unknown for >10% of MN and >50% of membranous lupus nephritis (MLN) cases. We identified multiple new targets in PLA2R-/THSD7A-/EXT-/NELL1-quadruple negative MN biopsies through mass spectrometry (MS) of immune complexes recovered from biopsy tissue of patients with MN. Methods: MN cases negative for PLA2R, THSD7A, EXT1/2, and NELL1 were identified from a biopsy database. Protein G immunoprecipitation was used to recover immune complexes from frozen biopsy tissue, followed by interrogation by mass spectrometry (MS). Potential antigens were confirmed through paraffin immunofluorescence of protein targets, followed by co-localization with IgG within immune deposits. Consecutive series of 165 cases of PLA2R-negative MN biopsies and 95 MLN biopsies was screened to determine the frequency for each potential antigen. Results: Seven protein targets were discovered within immune complexes from MN biopsies including FCN3, CD206, EEA1, SEZ6L2, NPR3, MST1, and VASN. Peptides from these proteins on MS were not enriched in PLA2R (n=86), THSD7A (n=64), NELL1 (n=64), or EXT1/2 (n=60) controls. Between 3-30 unique peptides were detected for each target. Frequencies of each antigen, determined by staining consecutive case series, were SEZ6L2 (1/165 idiopathic; 0/95 MLN), VASN (8/165 idiopathic; 2/95 MLN), EEA1 (6/165 idiopathic; 7/95 MLN), MST1 (6/165 idiopathic; 2/95 MLN), and FCN3 (0/165 idiopathic, 6/95 MLN), NPR3 and CD206 were positive in index cases. All cases showed co-localization of IgG within immune deposits. Conclusion: Seven novel protein targets were identified in MN and MLN.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Kidney

SUBMITTER: Aaron Storey  

LAB HEAD: Chris Larsen

PROVIDER: PXD035853 | Pride | 2023-04-06

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
Arkana_032521.sdia Other
Arkana_032521_Sample_01.dia.elib Other
Arkana_032521_Sample_01.raw Raw
Arkana_032521_Sample_02.dia.elib Other
Arkana_032521_Sample_02.raw Raw
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Publications

Discovery of seven novel putative antigens in membranous nephropathy and membranous lupus nephritis identified by mass spectrometry.

Caza Tiffany N TN   Storey Aaron J AJ   Hassen Samar I SI   Herzog Christian C   Edmondson Rick D RD   Arthur John M JM   Kenan Daniel J DJ   Larsen Christopher P CP  

Kidney international 20230110 3


Multiple autoantigens have been identified in membranous nephropathy (MN) by tissue-based proteomics. However, antigenic targets of disease are unknown for over 10% of patients with MN and over half of those with membranous lupus nephritis (MLN). Here, we identified multiple new targets in PLA2R-/THSD7A-/EXT-/NELL1-quadruple negative MN biopsies through mass spectrometry of immune complexes recovered from biopsy tissue of patients with MN. Patients with MN negative for these four antigens were i  ...[more]

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