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

Abstract

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 identified from Arkana Laboratories case archives. Protein G immunoprecipitation recovered immune complexes from frozen biopsy tissue from 142 quadruple-negative cases and 278 cases of known antigen type, followed by interrogation by mass spectrometry. Potential putative antigens were confirmed through paraffin immunofluorescence and co-localization with IgG within immune deposits. Consecutive series of 165 cases of PLA2R-negative MN and 142 MLN biopsies were screened to determine the frequency for each potential antigen. Seven putative antigens were discovered within immune complexes from biopsies of patients with MN including FCN3, CD206, EEA1, SEZ6L2, NPR3, MST1, and VASN. Peptides from these proteins were not enriched in the 278 cases of known antigen type. Between three to 30 unique peptides were detected for each new target. Frequencies of each biomarker, determined by staining consecutive case series, ranged from under 1 to 4.9%. NPR3 and CD206 were only positive in index cases. All cases showed co-localization of IgG within the immune deposits. Thus, seven putative antigens were newly identified in MN and MLN. Due to the number of antigens identified, it is becoming impractical to type PLA2R-negative MN or MLN cases through immunostaining alone. A multiplex approach is needed for subtyping of these diseases. 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 identified from Arkana Laboratories case archives. Protein G immunoprecipitation recovered immune complexes from frozen biopsy tissue from 142 quadruple-negative cases and 278 cases of known antigen type, followed by interrogation by mass spectrometry. Potential putative antigens were confirmed through paraffin immunofluorescence and co-localization with IgG within immune deposits. Consecutive series of 165 cases of PLA2R-negative MN and 142 MLN biopsies were screened to determine the frequency for each potential antigen. Seven putative antigens were discovered within immune complexes from biopsies of patients with MN including FCN3, CD206, EEA1, SEZ6L2, NPR3, MST1, and VASN. Peptides from these proteins were not enriched in the 278 cases of known antigen type. Between three to 30 unique peptides were detected for each new target. Frequencies of each biomarker, determined by staining consecutive case series, ranged from under 1 to 4.9%. NPR3 and CD206 were only positive in index cases. All cases showed co-localization of IgG within the immune deposits. Thus, seven putative antigens were newly identified in MN and MLN. Due to the number of antigens identified, it is becoming impractical to type PLA2R-negative MN or MLN cases through immunostaining alone. A multiplex approach is needed for subtyping of these diseases. Membranous nephropathy (MN) is a leading cause of nephrotic syndrome in adults and carries a high disease burden, with up to 16%–40% of patients developing kidney failure at 5–15 years.1Schieppati A. Mosconi L. Perna A. et al.Prognosis of untreated patients with idiopathic membranous nephropathy.N Engl J Med. 1993; 329: 85-89Crossref PubMed Scopus (371) Google Scholar, 2Lai W.L. Yeh T.H. Chen P.M. et al.Membranous nephropathy: a review on the pathogenesis, diagnosis, and treatment.J Formos Med Assoc. 2015; 114: 102-111Crossref PubMed Scopus (94) Google Scholar, 3Nazareth T.A. Kariburyo F. Kirkemo A. et al.Patients with idiopathic membranous nephropathy: a real-world clinical and economic analysis of U.S. claims data.J Manag Care Spec Pharm. 2019; 25: 1011-1020PubMed Google Scholar It is characterized by the presence of subepithelial immune complex deposits within glomeruli, which disrupt the glomerular filtration barrier and result in proteinuria. Traditionally, this disease has been designated as “primary” when there are no known associated diseases or “secondary” when certain diseases such as systemic lupus erythematosus or malignancy coincide. The main etiologies of “primary MN” were due to autoantibodies directed against the podocyte proteins phospholipase A2 receptor (PLA2R) in nearly 70% of cases4Beck L.H. Bonegio R.G. Lambeau G. et al.M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy.N Engl J Med. 2009; 361: 11-21Crossref PubMed Scopus (1687) Google Scholar and thrombospondin type 1 domain containing 7A (THSD7A) in approximately 3% of total MN.5Tomas N.M. Beck Jr., L.H. Meyer-Schwesinger C. et al.Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy.N Engl J Med. 2014; 371: 2277-2287Crossref PubMed Scopus (635) Google Scholar These renal-limited “primary” forms of MN were identified in 2009 and 2014, respectively. Before these discoveries, only 1 other antigenic type of MN was identified, MN due to antineutral endopeptidase antibodies, a very rare form that manifests in the antenatal and perinatal period.6Debiec H. Guigonis V. Mougenot B. et al.Antenatal membranous glomerulonephritis due to anti-neutral endopeptidase antibodies.N Engl J Med. 2002; 346: 2053-2060Crossref PubMed Scopus (451) Google Scholar Within the past 3 years alone, 10 new target antigens have been described in MN, including exostosin 1/2 (EXT1/2),7Sethi S. Madden B.J. Debiec H. et al.Exostosin 1/exostosin 2-associated membranous nephropathy.J Am Soc Nephrol. 2019; 30: 1123-1136Crossref PubMed Scopus (168) Google Scholar neural epidermal growth factor-like 1 (NELL1),8Sethi S. Debiec H. Madden B. et al.Neural epidermal growth factor-like 1 protein (NELL-1) associated membranous nephropathy.Kidney Int. 2020; 97: 163-174Abstract Full Text Full Text PDF PubMed Scopus (181) Google Scholar serine protease HTRA1 (HTRA1),9Al-Rabadi L.F. Caza T. Trivin-Avillach C. et al.Serine protease HTRA1 as a novel target antigen in primary membranous nephropathy.J Am Soc Nephrol. 2021; 32: 1666-1681Crossref PubMed Scopus (50) Google Scholar semaphorin 3B,10Sethi S. Debiec H. Madden B. et al.Semaphorin 3B-associated membranous nephropathy is a distinct type of disease predominantly present in pediatric patients.Kidney Int. 2020; 98: 1253-1264Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar protocadherin 7A (PCDH7A),11Sethi S. Madden B. Debiec H. et al.Protocadherin 7-associated membranous nephropathy.J Am Soc Nephrol. 2021; 32: 1249-1261Crossref PubMed Scopus (64) Google Scholar PCDH FAT1,12Sethi S. Madden B. Casal Moura M. et al.Hematopoietic stem cell transplant—membranous nephropathy is associated with protocadherin FAT1.J Am Soc Nephrol. 2022; 33: 1033-1044Crossref PubMed Scopus (27) Google Scholar netrin G1,13Reinhard L. Machalitza M. Wiech T. et al.Netrin G1 is a novel target antigen in primary membranous nephropathy.J Am Soc Nephrol. 2022; 33: 1823-1831Crossref PubMed Scopus (15) Google Scholar contactin 1 (CNTN1),14Le Quintrec M. Teisseyre M. Bec N. et al.Contactin-1 is a novel target antigen in membranous nephropathy associated with chronic inflammatory demyelinating polyneuropathy.Kidney Int. 2021; 100: 1240-1249Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar neural cell adhesion molecule-1 (NCAM1),15Caza T.N. Hassen S.I. Kuperman M. et al.Neural cell adhesion molecule 1 is a novel autoantigen in membranous lupus nephritis.Kidney Int. 2021; 100: 171-181Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar transforming growth factor beta receptor 3 (TGFBR3),16Caza T.N. Hassen S.I. Kenan D.J. et al.Transforming growth factor beta receptor 3 (TGFBR3)-associated membranous nephropathy.Kidney360. 2021; 2: 1275-1286Crossref PubMed Scopus (23) Google Scholar neural-derived neurotropic factor,17Sethi S. Madden B. Moura M.C. et al.Membranous nephropathy in syphilis is associated with neuron-derived neurotrophic factor. J Am Soc Nephrol.https://doi.org/10.1681/ASN.0000000000000061Google Scholar and proprotein convertase subtilisin/kexin type 6.18Sethi S. Casal Moura M. Madden B. Fervenza F.C. NSAID-associated membranous nephropathy (MN) is associated with PCSK6. American Society of Nephrology Annual Scientific Meeting, 2022Google Scholar The “primary” versus “secondary” classification of MN is becoming obsolete with the discovery of these multiple new antigenic drivers of disease, some of which have unique clinical characteristics or “secondary” associations.19Ronco P. Plaisier E. Debiec H. Advances in membranous nephropathy.J Clin Med. 2021; 10: 607Crossref PubMed Scopus (36) Google Scholar,20Bobart S.A. Tehranian S. Sethi S. et al.A target antigen-based approach to the classification of membranous nephropathy.Mayo Clin Proc. 2021; 96: 577-591Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar Despite the growing understanding about the pathogenesis of this disease, the target antigen remains unknown in approximately 15%–20% of cases that were formerly known as “primary” MN and approximately 55% of membranous lupus nephritis (MLN).21Caza T.N. L.F. Beck Jr., L.H. have A of antigens for membranous 2021; PubMed Scopus Google Scholar the antigenic target of disease in disease and for primary diagnosis, as has been for of with in idiopathic membranous J Am Soc Nephrol. 2014; PubMed Scopus Google Scholar, H. H. of autoantibodies and glomerular staining for the of idiopathic and membranous nephropathy: 2015; PubMed Scopus (64) Google Scholar, P. P. Debiec H. present clinical of membranous nephropathy.Kidney Int. Full Text Full Text PDF PubMed Scopus Google Scholar, et by in a of patients with idiopathic membranous nephropathy.Kidney Int. Full Text Full Text PDF PubMed Scopus Google Scholar, A. F. B. et of autoantibodies to phospholipase A2 receptor (PLA2R) in idiopathic membranous nephropathy from forms and other glomerular Nephrol. PubMed Scopus Google Scholar of the antigenic type about the of the patients with directed against have a chronic inflammatory demyelinating Quintrec M. Teisseyre M. Bec N. et al.Contactin-1 is a novel target antigen in membranous nephropathy associated with chronic inflammatory demyelinating polyneuropathy.Kidney Int. 2021; 100: 1240-1249Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar patients with MN with or as a putative antigen have a disease, such as systemic lupus S. Madden B.J. Debiec H. et al.Exostosin 1/exostosin 2-associated membranous nephropathy.J Am Soc Nephrol. 2019; 30: 1123-1136Crossref PubMed Scopus (168) Google T.N. Hassen S.I. Kuperman M. et al.Neural cell adhesion molecule 1 is a novel autoantigen in membranous lupus nephritis.Kidney Int. 2021; 100: 171-181Abstract Full Text Full Text PDF PubMed Scopus (67) Google T.N. Hassen S.I. Kenan D.J. et al.Transforming growth factor beta receptor 3 (TGFBR3)-associated membranous nephropathy.Kidney360. 2021; 2: 1275-1286Crossref PubMed Scopus (23) Google Scholar carries as patients with have a of to kidney A. Casal Moura M. Fervenza F.C. et patients with membranous lupus and Am Soc Nephrol. 2021; 32: PubMed Scopus Google M. E. et exostosin lupus membranous nephropathy with 2021; Full Text Full Text PDF PubMed Scopus Google Scholar The of other antigenic a of or the of certain such as or to such as et associated with neural epidermal growth factor-like 1 membranous nephropathy.Kidney Int. 2021; 100: Full Text Full Text PDF PubMed Scopus Google Scholar, T.N. in neural epidermal growth factor-like membranous nephropathy: a Int. 2022; Full Text Full Text PDF PubMed Scopus Google Scholar, N. M. as target antigen for membranous nephropathy: a case J Nephrol. 2022; 32: PubMed Scopus Google Scholar, P. Caza T.N. are for membranous nephropathy.Kidney Int. 2022; Full Text Full Text PDF PubMed Scopus Google Scholar diseases that are on a we that MN disease at the The antigens have been identified in idiopathic MN, with the antigens in a of patients with the cases are not of known antigen type. All known antigens and putative antigens in MN and MLN were identified by mass spectrometry the of which tissue-based These kidney biopsy tissue to for glomerular proteins by through of immune complexes through immunoprecipitation with protein G that T.N. L.F. Beck Jr., L.H. have A of antigens for membranous 2021; PubMed Scopus Google Scholar Here, we identified multiple novel in PLA2R-/THSD7A-/EXT-/NELL1-quadruple negative MN biopsies and MLN biopsies through protein G and putative antigen was confirmed by and the was screened in of MN and MLN All cases in this were from the clinical case at Arkana All were to a by review and and for the of in were biopsies were identified for the discovery from a biopsy to the of membranous on kidney by and by immunofluorescence and and MN was not the including kidney disease, disease, and were from the cases that were and as for known antigen type. negative for antigens were for were from of cases. 1 of a total of cases including MN cases. of a that cases in to cases of known antigen type. The of each in of in it is not to these discovery Protein were from kidney biopsy tissue frozen in were at with 1 of to with the the was with with the of protease and and of were to the followed by of the tissue a of were the the were a to tissue The was to protein containing of protein G were by at for 1 with The were to a with the The were with to protein the the were frozen at tissue was at 10 to were These were with The were with a were in and at for 1 and by was with a of 30 with in were to and the with was by 3 with followed by 3 with Protein was at a at for Peptides were by and on Peptides were through of the immune complexes to protein G was with for the and with from the were T.N. Hassen S.I. et is a target antigen in membranous nephropathy.Kidney Int. 2021; Full Text Full Text PDF PubMed Scopus Google Scholar was for analysis as was to peptides on a with a The peptides were with a of A from a to a over 1 was to the peptides on mass of a were on the mass with target in a to a et and by mass PubMed Scopus Google Scholar were each the of the from each were target followed by at target a with was to were against the from with 10 and to with a and protein discovery of were against the for and was on frozen tissue by for 3 1 receptor 3 antigen 1 of and was on tissue by paraffin These primary were and antigen FCN3, CD206, NPR3, SEZ6L2, and antigen at the EEA1, and were with The IgG was with the The IgG was for tissue to the other primary FCN3, MST1, EEA1, CD206, SEZ6L2, and frozen tissue was staining for IgG was tissue were in to were with and for 30 at in the were in and All were and the is as CD206 NPR3 IgG IgG IgG IgG and IgG IgG were from and at was by staining known negative cases for each including 3 cases each of MN, MN, MN, MN, and nephropathy cases. staining was a positive and cases were negative there was of staining the glomerular tissue were with IgG at were in and under a MN cases were in to cases of as negative of consecutive kidney biopsies were to determine the frequency for each These 165 PLA2R-negative MN and 142 cases of MLN. idiopathic MN biopsies in the of this consecutive were All cases were for each biomarker, including SEZ6L2, EEA1, MST1, NPR3, FCN3, and to immunostaining for each of the staining for and was on the MN the MLN immunostaining for and was These were to for or with each of the biopsies negative for and 142 total from discovery were by to new antigenic targets in MN protein G to from frozen biopsy These were with 278 cases of known antigen type, including and MN These cases were from discovery due to within and enriched protein to a potential target in MN in quadruple-negative the were by within protein G of frozen biopsy tissue with 3 or unique staining of the target protein by paraffin IgG of the target protein the glomerular and of staining glomerular with and protein that the we screened consecutive case of PLA2R-negative idiopathic MN and MLN to the frequency of each putative antigen in determine protein G of immune complexes was to to from tissue in subtyping MN cases by a of cases of known antigenic were by The antigen type was identified by protein G and was in 3 cases of MN, 3 cases of MN, cases of MN, cases of MN, 3 cases of MN, 1 case of MN, cases of MN, 1 case of semaphorin MN, 1 case of MN, cases of MN, and 1 case of netrin MN not These were for and L.F. Caza T. Trivin-Avillach C. et al.Serine protease HTRA1 as a novel target antigen in primary membranous nephropathy.J Am Soc Nephrol. 2021; 32: 1666-1681Crossref PubMed Scopus (50) Google T.N. Hassen S.I. Kuperman M. et al.Neural cell adhesion molecule 1 is a novel autoantigen in membranous lupus nephritis.Kidney Int. 2021; 100: 171-181Abstract Full Text Full Text PDF PubMed Scopus (67) Google T.N. Hassen S.I. Kenan D.J. et al.Transforming growth factor beta receptor 3 (TGFBR3)-associated membranous nephropathy.Kidney360. 2021; 2: 1275-1286Crossref PubMed Scopus (23) Google Scholar in the antigen we not protein G and for the discovery of new putative antigens and protein G was for cases. the 142 quadruple-negative MN biopsies by for a known antigen type, including netrin G1 PCDH semaphorin HTRA1 and a protein as a potential new target we for proteins in the that were enriched in unknown membranous as with of known antigen Seven biopsies showed the of a unique protein present within immune which were as potential target NPR3 and CD206 each protein as a in MN, we peptides of a putative antigen were present in the index cases by with other in as Protein were to determine a protein was in these cases with as 3 peptides were identified for each target with in for each target was as and protein unique peptides and for SEZ6L2, EEA1, MST1, NPR3, FCN3, and CD206 are in respectively. new target peptides showed of in the index cases a with cases. and CD206 were identified from a of cases and the were discovered from a of cases for each was with SEZ6L2, EEA1, and was with a total of including MN, MN, MN, and MN. and CD206 were discovered from a with MN, 3 MN, MN, and index cases and are in immunofluorescence identified positive staining within for each of the protein identified by that each of the target proteins with IgG the glomerular was no for of the targets with IgG in MN cases. of of antigen with IgG immune deposits are in and of within negative in All cases to the of paraffin immunofluorescence were A total of cases were for each putative including 3 3 3 3 and 3 nephropathy with positive cases in Consecutive series of 165 cases of PLA2R-negative MN and 142 cases of MLN were by paraffin immunofluorescence for each to the frequency in these cases were for known including and in MN and and in MLN cases. MN was positive in 1 of 165 in of 165 in of 165 in of 165 and in 1 of 165 and no cases of NPR3 or CD206 were cases were positive for antigens including 1 case and 1 case was positive in of 142 cases. cases of NPR3, or CD206 were identified in MLN cases cases were identified including 1 case and 1 The frequency of in this is to those described for other MN approximately of MN cases were to and positive and and Beck L.H. staining of membranous in clinical cases with Full Text Full Text PDF PubMed Scopus Google T. C. T. et membranous nephropathy with staining of exostosin 1/exostosin in the a of Med. 2021; Full Text Full Text PDF PubMed Scopus Google Scholar and of patients identified for these are in IgG staining was in cases with tissue for analysis These 1 and positive cases which was positive for FCN3, and biopsies were a of MN with biopsies IgG staining the of cases were from MLN biopsies identified novel putative antigens in MN through tissue-based proteomics. All were discovered by protein G a that was to discovery of other antigenic targets in kidney including T.N. Hassen S.I. Kuperman M. et al.Neural cell adhesion molecule 1 is a novel autoantigen in membranous lupus nephritis.Kidney Int. 2021; 100: 171-181Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar T.N. Hassen S.I. Kenan D.J. et al.Transforming growth factor beta receptor 3 (TGFBR3)-associated membranous nephropathy.Kidney360. 2021; 2: 1275-1286Crossref PubMed Scopus (23) Google Scholar L.F. Caza T. Trivin-Avillach C. et al.Serine protease HTRA1 as a novel target antigen in primary membranous nephropathy.J Am Soc Nephrol. 2021; 32: 1666-1681Crossref PubMed Scopus (50) Google Scholar and Caza T. Debiec H. et and protein are novel target antigens in Int. 2022; Full Text Full Text PDF PubMed Scopus Google Scholar of target antigens was through of each putative antigen with IgG within the subepithelial immune deposits. case series of MN biopsies was to determine antigenic analysis that 3 of the newly identified antigens were very rare of including CD206, SEZ6L2, and NPR3, of the antigens FCN3, EEA1, and were of these and EEA1, frequency in patients with MLN and to other known These in half of the autoantigens are known FCN3, EEA1, MST1, and and these putative antigens of PLA2R-negative idiopathic MN cases. only of MN cases are these new for only of idiopathic MN cases and of in antigen receptor of MN MLN beta and of immune immune type 1 to for characteristics are including protein within and for Frequencies of each in PLA2R-negative MN and MLN are against these target proteins were not in this three showed of in other disease in The presence or of each protein in was the protein and M. F. et al.A in of the podocyte kidney disease Full Text Full Text PDF PubMed Scopus Google Scholar, M. L. et of the 2015; PubMed Scopus Google Scholar, H. et of a kidney biopsy a inflammatory Am Soc Nephrol. PubMed Scopus Google membranous lupus MN, membranous phospholipase A2 in a new Protein characteristics are including protein within and for Frequencies of each in PLA2R-negative MN and MLN are against these target proteins were not in this three showed of in other disease in The presence or of each protein in was the protein and M. F. et al.A in of the podocyte kidney disease Full Text Full Text PDF PubMed Scopus Google Scholar, M. L. et of the 2015; PubMed Scopus Google Scholar, H. et of a kidney biopsy a inflammatory Am Soc Nephrol. PubMed Scopus Google Scholar membranous lupus MN, membranous phospholipase A2 identified protein as primary podocyte antigens or have “secondary” within All of these proteins are known to in M. F. et al.A in of the podocyte kidney disease Full Text Full Text PDF PubMed Scopus Google Scholar, M. L. et of the 2015; PubMed Scopus Google Scholar, H. et of a kidney biopsy a inflammatory Am Soc Nephrol. PubMed Scopus Google Scholar the of these proteins are within the including M. L. et of the 2015; PubMed Scopus Google Scholar M. et protein and protein are of in PubMed Scopus Google Scholar M. N. et a protein of the a in and PubMed Scopus Google Scholar C. A cell of neural 2009; 10: PubMed Scopus Google Scholar L. Chen P. et cell PubMed Scopus Google Scholar and M. T.A. et CD206 has potential as a of Google Scholar known MN antigens are by the and including et have of proteins and PubMed Scopus Google Scholar T. T. et in from those in the PubMed Scopus Google Scholar Quintrec M. Teisseyre M. Bec N. et al.Contactin-1 is a novel target antigen in membranous nephropathy associated with chronic inflammatory demyelinating polyneuropathy.Kidney Int. 2021; 100: 1240-1249Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar B.J. et in a 2020; PubMed Scopus Google Scholar S. E. N. et of and PubMed Scopus Google Scholar M. et with and and 2020; Scholar and semaphorin in neural and 2009; PubMed Scopus Google Scholar antigenic targets of MN and MLN discovered were discovered by protein the of these have been identified in potential for of the MN, with disease and in disease in clinical for of the disease, as as primary 3 of the new FCN3, EEA1, and SEZ6L2, have been identified, these proteins were not described to MN M. E. G. et the presence of autoantibodies and nephritis in patients with systemic lupus PubMed Scopus Google H. to a novel antigen PubMed Scopus Google Scholar against known as the have been identified in patients with systemic lupus S. H. et and of a or detected by in of patients with systemic lupus PubMed Scopus Google T. L. P. S. of in patients with systemic lupus 2009; PubMed Scopus Google Scholar and with the systemic lupus erythematosus disease as as of and M. E. G. et the presence of autoantibodies and nephritis in patients with systemic lupus PubMed Scopus Google Scholar against are in from patients with lupus H. to a novel antigen PubMed Scopus Google Scholar have been identified in patients with and have not been with or kidney M. M. et syndrome and 2021; PubMed Scopus Google Scholar against these other antigen identified within for potential of of the number of antigens identified, it is becoming impractical to type PLA2R-negative MN or MLN cases through immunostaining A multiplex approach is needed for subtyping of this is through which is and for the of the antigen type and has been for the discovery of known MN has been in as it is impractical to type by S. et and mass the and of Int. Full Text Full Text PDF PubMed Scopus Google H. H. et detected in a with complex of and PubMed Scopus Google Scholar is for antigenic subtyping are to identified in of MN and MLN. The of of are and primary a kidney as for MN in the glomerular disease clinical for the of glomerular Int. 2021; 100: Full Text Full Text PDF PubMed Scopus Google Scholar have as clinical and some patients at the of kidney not within for against these putative antigens is needed to staining of consecutive case series was to determine the frequency of each antigen in idiopathic MN and the number of identified cases for antigen is and it is unknown unique clinical this we not have from the patients with MN, which were not which we that of the identified putative antigens are However, is for each of these as these proteins with IgG and with IgG within glomerular immune deposits. Seven novel antigens were identified in MN through protein G of biopsy is to for and to determine unique characteristics or disease that this of these targets in MN.

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