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  1. Article: The Many Faces of NELL1 MN.

    Sethi, Sanjeev

    Clinical kidney journal

    2022  Volume 16, Issue 3, Page(s) 442–446

    Abstract: Neural tissue encoding protein with EGF-like repeats (NELL1) is a recently discovered target antigen in membranous nephropathy (MN). The initial study showed that most cases of NELL1 MN had no underlying disease associations, i.e. most cases of NELL1 MN ... ...

    Abstract Neural tissue encoding protein with EGF-like repeats (NELL1) is a recently discovered target antigen in membranous nephropathy (MN). The initial study showed that most cases of NELL1 MN had no underlying disease associations, i.e. most cases of NELL1 MN were classified as primary MN. Subsequently, NELL1 MN has been found in the setting of various diseases. These include NELL1 MN associated with malignancy, drugs, infections, autoimmune disease, hematopoietic stem cell transplant, de novo MN in a kidney transplant and sarcoidosis. Thus there is marked heterogeneity in the diseases associated with NELL1 MN. Evaluation of an underlying disease associated with MN will likely need to be more exhaustive in NELL1 MN.
    Language English
    Publishing date 2022-10-29
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2655800-2
    ISSN 2048-8513 ; 2048-8505
    ISSN (online) 2048-8513
    ISSN 2048-8505
    DOI 10.1093/ckj/sfac237
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    Zs.A 6587: Show issues Location:
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  2. Article: Membranous nephropathy: a single disease or a pattern of injury resulting from different diseases.

    Sethi, Sanjeev

    Clinical kidney journal

    2021  Volume 14, Issue 10, Page(s) 2166–2169

    Abstract: Membranous nephropathy (MN) is defined as disease entity characterized by thickening of the glomerular basement membranes due to subepithelial (SE) deposition of immune complexes. It is typically classified into primary MN (70%) when there is no disease ... ...

    Abstract Membranous nephropathy (MN) is defined as disease entity characterized by thickening of the glomerular basement membranes due to subepithelial (SE) deposition of immune complexes. It is typically classified into primary MN (70%) when there is no disease association, and secondary MN (30%) when there is an underlying disease association such as lupus, malignancy, infections or drugs. Phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) are target antigens in 70% and 1-5% of primary MN, respectively. The antigens in the remaining MN were not known. Recently, multiple novel proteins/target antigens have been identified in MN. These include exostosin 1/2, neural epidermal growth-like 1 protein, semaphorin 3B, protocadherin 7 and neural cell adhesion molecule 1. Some of these antigens are present in the setting of primary MN, some in secondary MN and some in both, thus blurring the lines between primary and secondary MN. Preliminary studies show that each of the new antigen-associated MN has distinct clinical, kidney biopsy findings and outcome data. We propose that each new protein/antigen-associated MN is a specific disease that results in the common MN pattern of injury characterized by thickened glomerular basement membrane (GBM) with or without spikes or pinholes on light microscopy, granular immunoglobulin G with or without complement 3 on immunofluorescence microscopy and SE electron-dense deposits on electron microscopy. In other words, MN is truly only a pattern of injury resulting from specific diseases that cause deposition of SE immune deposits along the GBM. It is of paramount importance to ascertain the specific disease entity causing the MN pattern not only for precise diagnosis and management, but also for future studies on these newly described diseases.
    Language English
    Publishing date 2021-03-26
    Publishing country England
    Document type Journal Article
    ZDB-ID 2655800-2
    ISSN 2048-8513 ; 2048-8505
    ISSN (online) 2048-8513
    ISSN 2048-8505
    DOI 10.1093/ckj/sfab069
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  3. Article ; Online: Mapping antigens of membranous nephropathy: almost there.

    Sethi, Sanjeev / Madden, Benjamin

    Kidney international

    2023  Volume 103, Issue 3, Page(s) 469–472

    Abstract: Membranous nephropathy (MN) is characterized by subepithelial accumulation of immune complexes along the glomerular basement membranes. The immune complexes compromise IgG and the corresponding target antigen. Recent advances have led to the discovery of ...

    Abstract Membranous nephropathy (MN) is characterized by subepithelial accumulation of immune complexes along the glomerular basement membranes. The immune complexes compromise IgG and the corresponding target antigen. Recent advances have led to the discovery of novel target MN antigens. In this study, by Caza et al., 7 novel "putative" antigens are proposed. Target antigens can now be identified in approximately 90% of cases of MN. In addition to describing another 10 novel putative antigens, we propose a working algorithm for evaluating the target antigens in MN.
    MeSH term(s) Humans ; Glomerulonephritis, Membranous ; Antigen-Antibody Complex ; Glomerular Basement Membrane
    Chemical Substances Antigen-Antibody Complex
    Language English
    Publishing date 2023-02-23
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 120573-0
    ISSN 1523-1755 ; 0085-2538
    ISSN (online) 1523-1755
    ISSN 0085-2538
    DOI 10.1016/j.kint.2023.01.003
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  4. Article ; Online: New 'Antigens' in Membranous Nephropathy.

    Sethi, Sanjeev

    Journal of the American Society of Nephrology : JASN

    2020  Volume 32, Issue 2, Page(s) 268–278

    Abstract: Membranous nephropathy (MN) occurs due to deposition of immune complexes along the subepithelial region of glomerular basement membrane. Two previously identified target antigens for the immune complexes, PLA2R (identified in 2009) and THSD7A (in 2014), ... ...

    Abstract Membranous nephropathy (MN) occurs due to deposition of immune complexes along the subepithelial region of glomerular basement membrane. Two previously identified target antigens for the immune complexes, PLA2R (identified in 2009) and THSD7A (in 2014), account for approximately 60% of all MN, both primary and secondary. In the remaining MN, target antigens were unknown. Use of laser microdissection and mass spectrometry enabled identification of new "antigens." This approach led to the identification of four novel types of MN: exotosin 1 (EXT1)- and exotosin 2 (EXT2)-associated MN, NELL1-associated MN, Sema3B-associated MN, and PCDH7-associated MN. Each of these represents a distinct disease entity, with different clinical and pathologic findings. In this review, the structure of the proteins and the clinical and pathologic findings of the new types of MN are discussed. The role of mass spectrometry for accurate diagnosis of MN cannot be overemphasized. Finally, any classification of MN should be made on the basis of the antigens that are detected. Further studies are required to understand the pathophysiology, response to treatment, and outcomes of these new MNs.
    MeSH term(s) Cadherins/immunology ; Calcium-Binding Proteins/immunology ; Glomerulonephritis, Membranous/diagnosis ; Glomerulonephritis, Membranous/etiology ; Humans ; Laser Capture Microdissection ; Membrane Glycoproteins/immunology ; N-Acetylglucosaminyltransferases/immunology ; Protocadherins ; Semaphorins/immunology ; Tandem Mass Spectrometry
    Chemical Substances Cadherins ; Calcium-Binding Proteins ; Membrane Glycoproteins ; NELL1 protein, human ; PCDH7 protein, human ; Protocadherins ; SEMA3B protein, human ; Semaphorins ; N-Acetylglucosaminyltransferases (EC 2.4.1.-) ; exostosin-1 (EC 2.4.1.224) ; exostosin-2 (EC 2.4.1.224)
    Language English
    Publishing date 2020-12-30
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1085942-1
    ISSN 1533-3450 ; 1046-6673
    ISSN (online) 1533-3450
    ISSN 1046-6673
    DOI 10.1681/ASN.2020071082
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    Zs.A 3344: Show issues Location:
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  5. Article ; Online: Membranous nephropathy-diagnosis and identification of target antigens.

    Sethi, Sanjeev / Fervenza, Fernando C

    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

    2023  Volume 39, Issue 4, Page(s) 600–606

    Abstract: Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. MN is characterized by subepithelial accumulation of immune complexes along the glomerular basement membrane. The immune complexes are composed of immunoglobulin G and a ... ...

    Abstract Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. MN is characterized by subepithelial accumulation of immune complexes along the glomerular basement membrane. The immune complexes are composed of immunoglobulin G and a target antigen. PLA2R is the target antigen in approximately 60% of MN cases, and MN is traditionally classified as PLA2R-positive or PLA2R-negative MN. Over the last 7 years, additional target antigens have been identified, which have specific disease associations, distinctive clinical and pathologic findings, and therapeutic implications. The newly discovered target antigens include NELL1, EXT1/EXT2, NCAM1, SEMA3B, PCDH7, FAT1, CNTN1, NTNG1, PCSK6 and NDNF. To group all these antigens into a generic 'PLA2R-negative' MN group is imprecise and un-informative. We propose a logical approach for detection of the target antigen which includes (i) currently available serology-based testing to detect anti-PLA2R and anti-THSD7A antibodies; and (ii) kidney biopsy testing to detect the target antigens. Determination of the antigen on kidney biopsy can be done by immunohistochemistry or immunofluorescence studies. Alternatively, laser capture microdissection (LCM) of glomeruli followed by mass spectrometry (MS) can be used to identify a target antigen. LCM/MS has the advantage of being a one-stop test and is particularly useful for detection of rare target antigens. At the current time, while it is possible to detect the newer antigens by immunohistochemistry/immunofluorescence/LCM/MS, serology-based tests to detect serum antibodies to the new antigens are not yet available. It is critical that serology-based tests should be developed not just for accurate diagnosis, but as a guide for treatment. We review the current methodology and propose an algorithm for diagnosis and detection of target antigens in MN that may shape the current practice in the future. Membranous nephropathy (MN) results from accumulation of subepithelial immune complexes along the glomerular basement membrane.PLA2R is the most common target antigen, but newly discovered target antigens have filled the void of PLA2R-negative MN.MN associated with the newly discovered target antigens have distinctive clinical and pathologic findings, treatment and prognostic implications. These include NELL1, EXT1/EXT2, NCAM1, PCDH7, SEMA3B, CNTN1, FAT1, NDNF and PCSK6.Immunohistochemistry/immunofluorescence methodology is currently in use for detecting target antigens in kidney biopsy tissue, although we anticipate laser capture microdissection of glomeruli followed by mass spectrometry will become available soon.Serologic testing is currently available for only detecting antibodies to PLA2R and THSD7A. It is critical that serologic tests become available for detecting antibodies to the newly discovered antigens.
    MeSH term(s) Adult ; Humans ; Glomerulonephritis, Membranous/diagnosis ; Antigen-Antibody Complex ; Autoantibodies ; Kidney Glomerulus/pathology ; Prognosis ; Receptors, Phospholipase A2
    Chemical Substances Antigen-Antibody Complex ; Autoantibodies ; Receptors, Phospholipase A2
    Language English
    Publishing date 2023-10-21
    Publishing country England
    Document type Review ; Journal Article
    ZDB-ID 90594-x
    ISSN 1460-2385 ; 0931-0509
    ISSN (online) 1460-2385
    ISSN 0931-0509
    DOI 10.1093/ndt/gfad227
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    Zs.A 2198: Show issues Location:
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    Zs.MO 329: Show issues

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  6. Article ; Online: The Changing Spectrum of Heroin-Associated Kidney Disease.

    Sethi, Sanjeev

    Clinical journal of the American Society of Nephrology : CJASN

    2018  Volume 13, Issue 7, Page(s) 975–976

    MeSH term(s) Amyloidosis ; Heroin ; Humans ; Kidney ; Kidney Diseases ; Northwestern United States
    Chemical Substances Heroin (70D95007SX)
    Language English
    Publishing date 2018-06-15
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 2226665-3
    ISSN 1555-905X ; 1555-9041
    ISSN (online) 1555-905X
    ISSN 1555-9041
    DOI 10.2215/CJN.06080518
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  7. Article ; Online: Direct Kidney Involvement by

    Mignano, Salvatore E / Kozeny, Gregory / Pritt, Bobbi S / Sethi, Sanjeev

    Kidney international reports

    2023  Volume 8, Issue 6, Page(s) 1260–1263

    Language English
    Publishing date 2023-03-13
    Publishing country United States
    Document type Case Reports
    ISSN 2468-0249
    ISSN (online) 2468-0249
    DOI 10.1016/j.ekir.2023.03.005
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  8. Article ; Online: Slowly Unraveling the Mysteries of C3G.

    Cattran, Daniel C / Sethi, Sanjeev

    American journal of kidney diseases : the official journal of the National Kidney Foundation

    2021  Volume 77, Issue 5, Page(s) 670–672

    MeSH term(s) Glucosides ; Humans ; Kidney Diseases
    Chemical Substances Glucosides
    Language English
    Publishing date 2021-02-11
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 604539-x
    ISSN 1523-6838 ; 0272-6386
    ISSN (online) 1523-6838
    ISSN 0272-6386
    DOI 10.1053/j.ajkd.2020.12.009
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  9. Article ; Online: Posaconazole-induced podocyte phospholipidosis.

    Gilani, Sarwat / Nasr, Samih H / Sethi, Sanjeev

    Kidney international

    2022  Volume 101, Issue 3, Page(s) 654

    MeSH term(s) Humans ; Lipidoses/chemically induced ; Podocytes ; Triazoles/adverse effects
    Chemical Substances Triazoles ; posaconazole (6TK1G07BHZ)
    Language English
    Publishing date 2022-02-01
    Publishing country United States
    Document type Case Reports
    ZDB-ID 120573-0
    ISSN 1523-1755 ; 0085-2538
    ISSN (online) 1523-1755
    ISSN 0085-2538
    DOI 10.1016/j.kint.2021.08.004
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  10. Article ; Online: A case of protocadherin FAT1-positive membranous nephropathy secondary to hematopoietic stem-cell transplantation.

    Mongera, Nicola / Passler, Werner / Sethi, Sanjeev / Kozakowski, Nicolas / Tabbì, Maria Grazia

    Journal of nephrology

    2023  

    Language English
    Publishing date 2023-10-10
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 1093991-x
    ISSN 1724-6059 ; 1120-3625 ; 1121-8428
    ISSN (online) 1724-6059
    ISSN 1120-3625 ; 1121-8428
    DOI 10.1007/s40620-023-01786-7
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